CN114672567A - Lung squamous carcinoma patient prognosis evaluation system based on CD47 and TIGIT double targets and application thereof - Google Patents

Lung squamous carcinoma patient prognosis evaluation system based on CD47 and TIGIT double targets and application thereof Download PDF

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CN114672567A
CN114672567A CN202210452237.8A CN202210452237A CN114672567A CN 114672567 A CN114672567 A CN 114672567A CN 202210452237 A CN202210452237 A CN 202210452237A CN 114672567 A CN114672567 A CN 114672567A
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cell lung
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杨震林
徐佳晨
彭岳
陈颖
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Cancer Hospital and Institute of CAMS and PUMC
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Abstract

The invention discloses a lung squamous carcinoma patient prognosis evaluation system based on double targets of CD47 and TIGIT and application thereof. The invention also discloses an application of a substance for detecting the expression level of CD47 and TIGIT in any one of the following (A1) - (A6): (A1) preparing a product for prognosis evaluation of a squamous cell lung carcinoma patient; (A2) preparing a product for predicting postoperative risk of a patient with squamous cell lung carcinoma; (A3) preparing a product for predicting the postoperative overall survival period of the squamous cell lung carcinoma patient; (A4) assessing prognosis of patients with squamous cell lung carcinoma; (A5) predicting postoperative risk of squamous cell lung carcinoma patients; (A6) predicting the postoperative overall survival time of the squamous cell lung carcinoma patient. The invention constructs a lung squamous carcinoma prognosis evaluation system based on double targets of CD47 and TIGIT, and verifies the lung squamous carcinoma prognosis evaluation system in a large-scale queue. Meanwhile, CD47 and TIGIT are potential immunotherapy targets of lung squamous cell carcinoma, and when prognosis is evaluated, a new method is provided for predicting the curative effect of immunotherapy by determining the expression level.

Description

Lung squamous carcinoma patient prognosis evaluation system based on CD47 and TIGIT double targets and application thereof
Technical Field
The invention belongs to the technical field of biomedicine, and particularly relates to a lung squamous carcinoma patient prognosis evaluation system based on double targets of CD47 and TIGIT and application thereof.
Background
Lung cancer is the cancer species with the highest morbidity and mortality in China. Of these, about 85% are non-small cell lung cancers (NSCLC) and squamous cell lung carcinoma (LUSC) accounts for about 25% -30% of NSCLC. Squamous cell lung carcinoma is common in males, elderly, and patients with smoking history, and mainly occurs in central airways. The 5-year survival rate of the patients with advanced lung squamous cell carcinoma is lower than 20 percent.
Prognosis of squamous cell lung carcinoma is related to various factors, such as TNM (Tumor, Node, Metastasis) staging, degree of Tumor differentiation, etc., which are widely used to guide clinical decision-making. However, these factors have not been sufficient to accurately assess the prognosis of patients with squamous cell lung carcinoma. Reports show that the 5-year total survival rate of patients with squamous cell lung carcinoma at the IA stage is only 63% -79%, which indicates that even in the same stage, patients with squamous cell lung carcinoma have great prognosis difference, and a new prognosis biomarker needs to be explored to guide the clinic. Although various biomarkers have been found to be associated with prognosis of patients with squamous cell lung carcinoma, they cannot be widely applied in clinical practice due to the complex method and lack of external verification.
Disclosure of Invention
The invention aims to solve the technical problem of rapidly and accurately evaluating the prognosis of a patient with squamous cell lung carcinoma.
In order to solve the above-mentioned problems, the present invention provides a novel use of a substance for detecting the expression level of CD47 and TIGIT.
The invention provides application of a substance for detecting CD47 and TIGIT expression level in any one of the following (A1) - (A6):
(A1) preparing a product for prognosis evaluation of a squamous cell lung carcinoma patient;
(A2) preparing a product for predicting postoperative risk of a patient with squamous cell lung carcinoma;
(A3) preparing a product for predicting the postoperative overall survival period of the squamous cell lung carcinoma patient;
(A4) assessing prognosis of patients with squamous cell lung carcinoma;
(A5) predicting postoperative risk of squamous cell lung carcinoma patients;
(A6) predicting the postoperative overall survival time of the squamous cell lung carcinoma patient.
In order to solve the technical problem, the invention also provides a system for evaluating the prognosis of the squamous cell lung carcinoma patient.
The lung squamous carcinoma patient prognosis evaluation system provided by the invention comprises a substance for detecting the expression level of CD47 and TIGIT; the application of the lung squamous carcinoma patient prognosis evaluation system is any one of the following (B1) - (B3):
(B1) assessing prognosis of patients with squamous cell lung carcinoma;
(B2) predicting postoperative risk of squamous cell lung carcinoma patients;
(B3) predicting the postoperative overall survival time of the squamous cell lung carcinoma patient.
In any one of the applications or systems, the substance for detecting the expression level of CD47 and TIGIT comprises reagents and/or instruments required for detecting the expression level of CD47 and TIGIT on the protein level.
Further, the reagents required for detecting the expression level of the CD47 and the TIGIT on the protein level comprise antibodies required for detecting the expression level of the CD47 on the protein level by immunohistochemistry and antibodies required for detecting the expression level of the TIGIT on the protein level by immunohistochemistry.
Furthermore, the antibodies required for detecting the expression level of the CD47 on the protein level by using immunohistochemistry comprise a CD47 primary antibody (EPR21794, Abcam) and a secondary antibody from a corresponding source thereof; the antibodies required for detecting the expression quantity of the TIGIT on the protein level by the immunohistochemistry comprise TIGIT primary antibody (E5Y1W, CST) and secondary antibodies from corresponding sources.
In any of the above applications or systems, the substance for detecting the expression level of CD47 and TIGIT comprises reagents and/or instruments required for detecting the expression level of CD47 and TIGIT on the RNA level.
Further, the reagents required for detecting the expression amounts of CD47 and TIGIT on the RNA level comprise reagents required for detecting the expression amounts of CD47 and TIGIT on the RNA level by a transcriptome sequencing method or reagents required for detecting the expression amounts of CD47 and TIGIT on the RNA level by a quantitative PCR method.
Further, the reagents required for detecting the expression level of CD47 and TIGIT on the RNA level by using the transcriptome sequencing method include various reagents required for sequencing based on a transcriptome sequencing platform (such as Illumina high-throughput sequencing platform).
The reagents required for detecting the expression quantity of the CD47 and TIGIT on the RNA level by using a quantitative PCR method comprise a CD47 amplification primer and a TIGIT amplification primer.
In any one of the above applications or systems, the substance for detecting the expression levels of CD47 and TIGIT further comprises a data processing device a; a module is arranged in the data processing device A; the module has the functions as shown in (a1) and (a 2):
(a1) respectively determining the TIGIT positive tumor infiltration lymphocyte density and the percentage of CD47 positive tumor cells in the tumor tissue of each patient in a population to be tested consisting of a plurality of lung squamous carcinoma patients; arranging and halving the population to be detected according to the sequence of the TIGIT positive tumor infiltrating lymphocyte density from low to high, taking 1/2 the population to be detected with low TIGIT positive tumor infiltrating lymphocyte density as a TIGIT low-density group, and taking the rest 1/2 the population to be detected as a TIGIT high-density group; determining whether the patients with squamous cell lung carcinoma are CD47 negative or CD47 negative according to the percentage of CD47 positive tumor cells, wherein the patients with squamous cell lung carcinoma with the percentage of CD47 positive tumor cells more than or equal to 5 percent are CD47 positive, and the patients with squamous cell lung carcinoma with the percentage of CD47 positive tumor cells less than 5 percent are CD47 negative; taking squamous cell lung carcinoma patients which belong to a TIGIT high-density group and are positive to CD47 in a population to be detected as a dual high expression group, and taking the rest squamous cell lung carcinoma patients as a non-dual high expression group;
(a2) determining the overall post-operative survival of patients with squamous cell lung carcinoma from the test population according to the following criteria: the overall survival of patients with squamous cell lung carcinoma in the dual high expression panel was shorter than that of patients with squamous cell lung carcinoma in the non-dual high expression panel.
In any one of the above applications or systems, the substance for detecting the expression levels of CD47 and TIGIT further comprises a data processing device b; a module is arranged in the data processing device B; the module has functions as shown in (b1) and (b 2):
(b1) separately determining the expression level of TIGIT and CD47 on RNA level in tumor tissue of each patient in a test population consisting of a plurality of patients with squamous cell lung carcinoma; and (3) grouping the populations to be tested according to the expression level of TIGIT and CD47 on the RNA level: arranging and halving the population to be detected according to the sequence of the expression level of TIGIT on the RNA level from low to high, taking 1/2 with low expression level as a TIGIT low expression group, taking the rest 1/2 population to be detected as TIGIT high expression groups, arranging and halving the population to be detected according to the sequence of the expression level of CD47 on the RNA level from low to high, taking 1/2 with low expression level as a CD47 low expression group, and taking the rest 1/2 population to be detected as a CD47 high expression group; taking the squamous cell lung carcinoma patients belonging to a TIGIT high expression group and a CD47 high expression group in the population to be detected as a double high expression group, and taking the rest squamous cell lung carcinoma patients as a non-double high expression group;
(b2) determining the overall post-operative survival of patients with squamous cell lung carcinoma from the test population according to the following criteria: the overall survival of patients with squamous cell lung carcinoma in the dual high expression panel was shorter than that of patients with squamous cell lung carcinoma in the non-dual high expression panel.
In any one of the above applications or systems, the expression level of TIGIT and CD47 at the RNA level can be obtained by a transcriptome sequencing method. In a specific embodiment of the invention, the TIGIT high expression group patient is a squamous cell lung carcinoma patient having a TIGIT transcript level greater than or equal to 0.994755; the TIGIT low expression group patient refers to a lung squamous carcinoma patient with a TIGIT transcription level less than or equal to 0.990942; the CD47 high expression group patients refer to lung squamous carcinoma patients with CD47 transcription level being more than or equal to 16.87126; the CD47 low expression group patient refers to lung squamous carcinoma patient with CD47 transcription level less than or equal to 16.86643.
The TIGIT positive tumor infiltrating lymphocyte density is the average value of the number of TIGIT positive tumor infiltrating lymphocytes under each high-power visual field, and the TIGIT positive tumor infiltrating lymphocytes refer to infiltrating lymphocytes which can be stained when TIGIT antibody immunohistochemical experiments are carried out. The TIGIT positive tumor infiltrating lymphocyte density can be obtained by the following method: and randomly selecting 6 fields under the multiplied by 400 field, counting the number of TIGIT positive tumor infiltrating lymphocytes under each field, and taking the average value, namely the TIGIT positive tumor infiltrating lymphocyte density.
The percentage of the CD 47-positive tumor cells is the percentage of CD 47-positive tumor cells in all tumor cells, and the CD 47-positive tumor cells refer to tumor cells of which the cell membranes can be stained in an immunohistochemical experiment of a CD47 antibody.
In order to solve the technical problems, the invention also provides a new application of TIGIT and CD47 as markers.
The invention provides the use of TIGIT and CD47 as markers or immunotherapeutic targets in any one of the following (a1) - (a 6):
(A1) preparing a product for prognosis evaluation of a squamous cell lung carcinoma patient;
(A2) preparing a product for predicting postoperative risk of a patient with squamous cell lung carcinoma;
(A3) preparing a product for predicting the postoperative overall survival period of the squamous cell lung carcinoma patient;
(A4) assessing prognosis of patients with squamous cell lung carcinoma;
(A5) predicting postoperative risk of squamous cell lung carcinoma patients;
(A6) predicting the postoperative overall survival time of the squamous cell lung carcinoma patient.
In any of the above applications or systems, the overall survival time (OS) is the time from the date of the operation to the date of the last follow-up or death.
In any of the uses or systems described above, the patient with squamous cell lung carcinoma is a patient with squamous cell lung carcinoma who has undergone surgery (lobectomy or total lung resection, systemic lymphadenectomy).
In any of the above applications or systems, the amino acid sequence of CD47 is shown as sequence 1 in the sequence listing. The amino acid sequence of the TIGIT is shown as a sequence 2 in a sequence table.
The lung squamous carcinoma prognosis evaluation system based on double targets of CD47 and TIGIT is constructed based on relatively easy-to-implement experimental technology, and is verified in a large-scale queue. Meanwhile, CD47 and TIGIT are potential immunotherapy targets of lung squamous cell carcinoma, and when prognosis is evaluated, a new method is provided for predicting the curative effect of immunotherapy by determining the expression level.
Drawings
FIG. 1 is an immunohistochemical staining image. A is positive for CD 47; b is CD47 negative; c is TIGIT high density; d is TIGIT low density.
Fig. 2 is a survival curve for the dual high expression group of CD47 and TIGIT from the LUSC cohort of the TCGA database.
FIG. 3 is the survival curves of the dual high expression group of CD47 and TIGIT derived from LUSC cohort of the pathology department of the tumor hospital of the Chinese academy of medicine sciences.
Detailed Description
The present invention is described in further detail below with reference to specific embodiments, which are given for the purpose of illustration only and are not intended to limit the scope of the invention. The examples provided below serve as a guide for further modifications by a person skilled in the art and do not constitute a limitation of the invention in any way.
The experimental procedures in the following examples, unless otherwise indicated, are conventional and are carried out according to the techniques or conditions described in the literature in the field or according to the instructions of the products. Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.
Overall Survival (OS) in the following examples is defined as the time from the date of surgery to the date of last follow-up or death.
Overall survival in the examples described below is defined as the proportion of patients who survive a particular time point following the lus cohort.
The amino acid sequence of CD47 in the following examples is shown as sequence 1 in the sequence table.
The amino acid sequence of TIGIT in the following examples is shown as sequence 2 in the sequence table.
Example 1, TIGIT and CD47 use as markers for prognostic assessment in patients with squamous cell lung carcinoma
Application of substance for detecting expression level of TIGIT and CD47 on RNA level in prognosis evaluation of squamous cell lung carcinoma patient
1. Study subject and method
Clinical information including age, sex, stage, etc. was extracted from The Cancer Genome Atlas (TCGA) database for 479 patients with lung squamous carcinoma lucs who underwent surgery. The clinical pathological features are shown in table 1. Median age: age 68 (age 39-85), male: 353 cases (73.7%), stage: 234 cases (48.9%) of stage I; 156 cases (32.5%) in phase II; stage III 83 cases (17.3%); stage IV 6 cases (1.3%).
Transcriptome data of 479 patients with lung squamous carcinoma LUSC who had undergone surgery were extracted from TCGA database, and the expression amounts (transcription levels) of TIGIT and CD47 at RNA level were obtained and expressed as FPKM. Dividing 479 LUSC patients into TIGIT high expression group (TIGIT high expression group patient refers to LUSC patient with TIGIT transcription level greater than or equal to 0.994755), TIGIT low expression group (TIGIT low expression group patient refers to LUSC patient with TIGIT transcription level less than or equal to 0.990942) according to TIGIT median transcription level; based on the median transcript level of CD47, 479 patients with lus were divided into a group with high CD47 expression (patients with high CD47 expression refers to patients with lus with CD47 transcript level greater than or equal to 16.87126), and a group with low CD47 expression (patients with low CD47 expression refers to patients with lus with CD47 transcript level less than or equal to 16.86643).
If a patient with LUSC belongs to both TIGIT high expression group and CD47 high expression group, the patient is defined as TIGIT and CD47 double high expression patient and belongs to TIGIT and CD47 double high expression group. A total of 142 (29.6%) of 479 patients with lucs belonged to the TIGIT and CD47 dual high expression group.
TABLE 1 clinical pathological characteristics and prognostic analysis of LUSC patients in TCGA database
Figure BDA0003619159420000051
2. Statistical analysis of data
Statistical analysis of the data was performed using SPSS software v.26.0. And (4) drawing an overall survival curve by adopting a Kaplan-Meier method. The significance of the differences between the survival curves of each group was calculated using the log-rank test. And (4) carrying out multifactorial analysis by adopting a COX proportional risk model. The difference was statistically defined as p < 0.05.
3. Survival analysis results
Median follow-up period in the LUSC cohort in TCGA database was 18.3 months (0.1-176.2 months). Survival analysis used the Kaplan-Meier curve. Higher T-stage, higher TNM stage, high CD47 expression and TIGIT/CD47 dual high expression were found to correlate with shorter Overall Survival (OS) in single factor analysis (T-stage, p 0.001; TNM stage, p 0.005; CD47 high expression, p 0.022; TIGIT/CD47 dual high expression, p 0.049). In the multifactorial analysis, TNM staging (p ═ 0.006) and TIGIT/CD47 dual high expression (p ═ 0.047) were found to be independent prognostic factors for the patients with luxc (table 1, fig. 2).
In practical application, the total postoperative life span of the squamous cell lung carcinoma patient can be predicted according to the following method: tumor tissues of a test population consisting of a plurality of patients with lung squamous carcinoma are taken as samples, the expression level of TIGIT and CD47 on the RNA level in each sample is respectively determined, and then the test population is divided into groups according to the expression level of TIGIT and CD47 on the RNA level: arranging and bisecting the populations to be detected according to the sequence that the expression level of TIGIT on the RNA level is from low to high, arranging and bisecting 1/2 the populations to be detected with low expression level as a TIGIT low expression group, taking the rest 1/2 the populations to be detected as TIGIT high expression groups, arranging and bisecting the populations to be detected according to the sequence that the expression level of CD47 on the RNA level is from low to high, taking 1/2 the populations to be detected with low expression level as a CD47 low expression group, taking the rest 1/2 the populations to be detected as a CD47 high expression group, finally taking the lung cancer patients belonging to the TIGIT high expression group and the CD47 high expression group in the populations to be detected as a double high expression group, taking the rest lung squamous cancer patients as a non-double high expression group, and predicting the postoperative total survival period of the lung squamous cancer patients from the populations to be detected according to the following standards: the overall survival of patients with squamous cell lung carcinoma in the dual high expression panel was shorter than that of patients with squamous cell lung carcinoma in the non-dual high expression panel.
Application of substance for detecting expression level of TIGIT and CD47 on protein level in prognosis evaluation of squamous cell lung carcinoma patient
1. Study subject and method
Data were collected retrospectively from 190 LUSC patients who underwent thoracic surgery at the tumor hospital of the Chinese academy of medicine in 2006-4-2011-2 months. All patients underwent lobar or total lung resection and systemic lymph node dissection. The standard of postoperative staging is referred to lung cancer TNM staging, 8 th edition. And retrospectively collecting data such as sex, age, smoking history, operation mode, postoperative pathological report, staging and the like in the medical record system. The clinical pathology of 190 patients with LUSC is shown in Table 2. Median age: the patients are 61 years old (37-79 years old), and are treated by operation; male: 183 cases (96.3%); there is a history of smoking: 176 cases (92.6%); poorly differentiated tumors: 95 cases (50.0%); staging: 34 cases (17.9%) in stage I, 70 cases (36.8%) in stage II, and 86 cases (45.3%) in stage III. The last follow-up time for all patients was 2018, 9 and 20.
FFPE (formalin fixed paraffin embedded) specimens of tumor tissues of 190 patients of the lucs from the pathology department of the tumor hospital of the academy of chinese medical science (patients all informed consent) were taken to construct Tissue Microarrays (TMAs) for immunohistochemical staining. The method comprises the following specific steps: 1) dewaxed in xylene and rehydrated in ethanol at different concentration gradients. 2) Antigen retrieval was performed by soaking in boiling citrate buffer (pH6.0) for 15 minutes. 3) Sections were incubated with 3% H at room temperature2O2Blocking was performed for 10 min, then incubated overnight at 4 ℃ using TIGIT primary antibody (E5Y1W, CST) and CD47 primary antibody (EPR21794, Abcam). 4) Three washes with TBS buffer were performed to remove the primary antibody. 5) A secondary antibody from the corresponding source (murine or rabbit) was added dropwise and incubated at room temperature for 30 minutes. 6) TBS buffer three times, add avidin-biotin complex dropwise, and incubate at room temperature for 45 minutes. 7) TBS buffer solution washing three times, DAB dark color (specific time according to experimental observation color development results confirmed). 8) Washing with water, slightly staining with hematoxylin, bluing, dehydrating, transparentizing, sealing with gum, and fixing.
Selecting 6 visual fields randomly under a high power visual field (multiplied by 400), counting the number of TIGIT positive tumor infiltrating lymphocytes (the TIGIT positive tumor infiltrating lymphocytes refer to infiltrating lymphocytes which can be stained by an immunohistochemical experiment by using a TIGIT antibody as a primary antibody) under each visual field, taking the average value of the number of the TIGIT positive tumor infiltrating lymphocytes, obtaining the number of the TIGIT positive tumor infiltrating lymphocytes under each high power visual field, namely the TIGIT positive Tumor Infiltrating Lymphocyte (TILs) density, and dividing 190 cases of LUSC patients into a TIGIT low density group and a TIGIT high density group according to the TILs density median.
The percentage of all tumor cells in the whole section that were CD47 positive (CD47 positive tumor cells means tumor cells that were stained with the CD47 antibody as a primary antibody in immunohistochemical experiments). A patient is defined as CD47 negative when the percentage of CD47 positive tumor cells in the patient is less than 5%, and as CD47 positive when the percentage of CD47 positive tumor cells in the patient is greater than or equal to 5%.
If a patient belongs to the TIGIT high density group and is positive for CD47, the patient is defined as a TIGIT and CD47 dual high expression patient belonging to the TIGIT and CD47 dual high expression group. TIGIT and CD47 immunohistochemical staining results are shown in fig. 1, with a total of 124 (65.3%) of 190 patients with lucs being CD47 positive and 75 (39.5%) belonging to the TIGIT and CD47 dual high expression group.
TABLE 2, 190 patients with squamous cell lung carcinoma, clinical pathology and prognostic analysis
Figure BDA0003619159420000071
Figure BDA0003619159420000081
2. Statistical analysis of data
Statistical analysis of the data was performed using SPSS software v.26.0. And (4) drawing an overall survival curve by adopting a Kaplan-Meier method. The significance of the differences between the survival curves of each group was calculated using the log-rank test. And (4) carrying out multifactorial analysis by adopting a COX proportional risk model. The difference was statistically defined as p < 0.05.
3. Survival analysis results
In the LUSC cohort, the 5-year overall survival (OS rate) was 68.4%, with a median survival time of 65 months. Survival analysis used the Kaplan-Meier curve. Higher T phase, N phase, TNM phase, TIGIT positive TILs high density, CD47 positive and TIGIT/CD47 dual high expression were found to correlate with shorter OS in single factor analysis (T phase, p < 0.001; N phase, p < 0.001; TNM phase, p < 0.001; CD47 positive, p 0.003; TIGIT positive TIL high density, p 0.027; CD47/TIGIT dual high expression, p 0.020). Advanced age, higher TNM staging and TIGIT/CD47 dual high expression were found in the multifactorial analysis to be independent prognostic factors for the LUSC patients (age, p 0.001; TNM staging, p < 0.001; TIGIT/CD47 dual high expression, p 0.046) (table 2, fig. 3).
In practical application, the total postoperative life span of the squamous cell lung carcinoma patient can be predicted according to the following method: tumor tissues of a to-be-detected population consisting of a plurality of lung squamous carcinoma patients are taken as samples, the TIGIT positive tumor infiltrating lymphocyte density and the percentage of CD47 positive tumor cells in each sample are respectively determined, then the to-be-detected population is arranged and equally divided according to the sequence of the TIGIT positive tumor infiltrating lymphocyte densities from low to high, 1/2 with low TIGIT positive tumor infiltrating lymphocyte densities is taken as a TIGIT low-density group, the rest 1/2 to-be-detected population is taken as a TIGIT high-density group, whether the lung squamous carcinoma patients are CD47 negative or CD47 negative is determined according to the percentage of the CD47 positive tumor cells, the lung squamous carcinoma patients with the percentage of the CD47 positive tumor cells being more than or equal to 5 percent are CD47 positive, the lung squamous carcinoma patients with the percentage of the CD47 positive tumor cells being less than 5 percent are CD47 negative, and finally the lung squamous carcinoma patients belonging to-lung carcinoma groups with the TIGIT high-density group and being CD47 positive in the to-be-detected population are taken as a double high-expression group, the remaining squamous cell lung carcinoma patients were taken as the non-dual high expression panel and the overall postoperative survival of squamous cell lung carcinoma patients from the test population was predicted according to the following criteria: the overall survival of patients with squamous cell lung carcinoma in the dual high expression panel was shorter than that of patients with squamous cell lung carcinoma in the non-dual high expression panel.
The present invention has been described in detail above. It will be apparent to those skilled in the art that the invention can be practiced in a wide range of equivalent parameters, concentrations, and conditions without departing from the spirit and scope of the invention and without undue experimentation. While the invention has been described with reference to specific embodiments, it will be appreciated that the invention can be further modified. In general, this application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains. The use of some of the essential features is possible within the scope of the claims attached below.
Sequence listing
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<120> lung squamous carcinoma patient prognosis evaluation system based on CD47 and TIGIT double targets and application thereof
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Claims (10)

1. The use of a substance for detecting the expression level of CD47 and TIGIT in any one of the following (A1) to (A6):
(A1) preparing a product for prognosis evaluation of a squamous cell lung carcinoma patient;
(A2) preparing a product for predicting postoperative risk of a patient with squamous cell lung carcinoma;
(A3) preparing a product for predicting the postoperative overall survival period of the squamous cell lung carcinoma patient;
(A4) assessing prognosis of patients with squamous cell lung carcinoma;
(A5) predicting postoperative risk of squamous cell lung carcinoma patients;
(A6) predicting the postoperative overall survival period of the patient with squamous cell lung carcinoma.
2. Use according to claim 1, characterized in that: the substance for detecting the expression quantity of the CD47 and the TIGIT comprises reagents and/or instruments required for detecting the expression quantity of the CD47 and the TIGIT on the protein level.
3. Use according to claim 2, characterized in that: the reagents required for detecting the expression level of the CD47 and the TIGIT on the protein level comprise antibodies required for detecting the expression level of the CD47 on the protein level by immunohistochemistry and antibodies required for detecting the expression level of the TIGIT on the protein level by immunohistochemistry.
4. Use according to claim 1, characterized in that: the substance for detecting the expression level of CD47 and TIGIT comprises reagents and/or instruments required for detecting the expression level of CD47 and TIGIT on the RNA level.
5. Use according to any one of claims 1 to 4, characterized in that: the substance for detecting the expression level of the CD47 and TIGIT also comprises a data processing device A; a module is arranged in the data processing device A; the module has the functions shown in (a1) and (a2) as follows:
(a1) respectively determining the TIGIT positive tumor infiltration lymphocyte density and the percentage of CD47 positive tumor cells in the tumor tissue of each patient in a population to be detected, which consists of a plurality of lung squamous carcinoma patients; arranging and halving the population to be detected according to the sequence of the TIGIT positive tumor infiltrating lymphocyte density from low to high, taking 1/2 the population to be detected with low TIGIT positive tumor infiltrating lymphocyte density as a TIGIT low-density group, and taking the rest 1/2 the population to be detected as a TIGIT high-density group; determining whether the patients with squamous cell lung carcinoma are CD47 negative or CD47 negative according to the percentage of CD47 positive tumor cells, wherein the patients with squamous cell lung carcinoma with the percentage of CD47 positive tumor cells more than or equal to 5 percent are CD47 positive, and the patients with squamous cell lung carcinoma with the percentage of CD47 positive tumor cells less than 5 percent are CD47 negative; taking squamous cell lung carcinoma patients which belong to a TIGIT high-density group and are positive to CD47 in a population to be detected as a dual high expression group, and taking the rest squamous cell lung carcinoma patients as a non-dual high expression group;
(a2) determining the overall post-operative survival of patients with squamous cell lung carcinoma from said test population according to the following criteria: the overall survival of patients with squamous cell lung carcinoma in the dual high expression panel was shorter than that of patients with squamous cell lung carcinoma in the non-dual high expression panel.
6. The system according to any one of claims 1-5, wherein: the substance for detecting the expression level of the CD47 and TIGIT also comprises a data processing device B; a module is arranged in the data processing device B; the module has functions as shown in (b1) and (b 2):
(b1) separately determining the expression level of TIGIT and CD47 at the RNA level in the tumor tissue of each patient in a test population consisting of a plurality of patients with squamous cell lung carcinoma; and (3) grouping the populations to be tested according to the expression level of TIGIT and CD47 on the RNA level: arranging and halving the population to be detected according to the sequence of the expression level of TIGIT on the RNA level from low to high, taking 1/2 with low expression level as a TIGIT low expression group, taking the rest 1/2 population to be detected as TIGIT high expression groups, arranging and halving the population to be detected according to the sequence of the expression level of CD47 on the RNA level from low to high, taking 1/2 with low expression level as a CD47 low expression group, and taking the rest 1/2 population to be detected as a CD47 high expression group; taking the squamous cell lung carcinoma patients belonging to a TIGIT high expression group and a CD47 high expression group in the population to be detected as a double high expression group, and taking the other squamous cell lung carcinoma patients as a non-double high expression group;
(b2) determining the overall post-operative survival of patients with squamous cell lung carcinoma from said test population according to the following criteria: the overall survival of patients with squamous cell lung carcinoma in the dual high expression panel was shorter than that of patients with squamous cell lung carcinoma in the non-dual high expression panel.
7. A squamous cell lung carcinoma patient prognosis evaluation system, which comprises a substance for detecting the expression level of CD47 and TIGIT; the application of the lung squamous cancer patient prognosis evaluation system is any one of the following (B1) - (B3):
(B1) assessing prognosis of patients with squamous cell lung carcinoma;
(B2) predicting postoperative risk of squamous cell lung carcinoma patients;
(B3) predicting the postoperative overall survival time of the squamous cell lung carcinoma patient.
8. The system of claim 7, wherein: the substance for detecting the expression level of CD47 and TIGIT comprises reagents and/or instruments required for detecting the expression level of CD47 and TIGIT on the RNA level;
or the substance for detecting the expression quantity of the CD47 and the TIGIT comprises reagents and/or instruments required for detecting the expression quantity of the CD47 and the TIGIT on the protein level.
9. The system according to any one of claims 6-8, wherein: the substance for detecting the expression level of the CD47 and TIGIT also comprises a data processing device A; a module is arranged in the data processing device A; the module has the functions as shown in (a1) and (a 2):
(a1) respectively determining the TIGIT positive tumor infiltration lymphocyte density and the percentage of CD47 positive tumor cells in the tumor tissue of each patient in a population to be detected, which consists of a plurality of lung squamous carcinoma patients; arranging and bisecting the to-be-detected populations according to the sequence of the TIGIT positive tumor infiltrating lymphocyte density from low to high, taking 1/2 of the to-be-detected populations with low TIGIT positive tumor infiltrating lymphocyte density as TIGIT low-density groups, and taking the rest 1/2 of the to-be-detected populations as TIGIT high-density groups; determining whether the patients with squamous cell lung carcinoma are CD47 negative or CD47 negative according to the percentage of CD47 positive tumor cells, wherein the patients with squamous cell lung carcinoma with the percentage of CD47 positive tumor cells more than or equal to 5 percent are CD47 positive, and the patients with squamous cell lung carcinoma with the percentage of CD47 positive tumor cells less than 5 percent are CD47 negative; taking squamous cell lung carcinoma patients which belong to a TIGIT high-density group and are positive to CD47 in a population to be detected as a dual high expression group, and taking the rest squamous cell lung carcinoma patients as a non-dual high expression group;
(a2) determining the overall post-operative survival of patients with squamous cell lung carcinoma from said test population according to the following criteria: the overall survival of patients with squamous cell lung carcinoma in the double high expression group is shorter than that of patients with squamous cell lung carcinoma in the non-double high expression group;
or the substance for detecting the expression level of the CD47 and TIGIT also comprises a data processing device B; a module is arranged in the data processing device B; the module has functions as shown in (b1) and (b 2):
(b1) separately determining the expression level of TIGIT and CD47 at the RNA level in the tumor tissue of each patient in a test population consisting of a plurality of patients with squamous cell lung carcinoma; grouping the populations to be tested according to the expression level of TIGIT and CD47 on RNA level: arranging and bisecting the to-be-detected populations according to the sequence of TIGIT expression level from low to high on the RNA level, using 1/2 the to-be-detected populations with low expression level as TIGIT low expression groups, using the rest 1/2 the to-be-detected populations as TIGIT high expression groups, arranging and bisecting the to-be-detected populations according to the sequence of CD47 expression level from low to high on the RNA level, using 1/2 the to-be-detected populations with low expression level as CD47 low expression groups, and using the rest 1/2 the to-be-detected populations as CD47 high expression groups; taking the squamous cell lung carcinoma patients belonging to a TIGIT high expression group and a CD47 high expression group in the population to be detected as a double high expression group, and taking the other squamous cell lung carcinoma patients as a non-double high expression group;
(b2) determining the overall post-operative survival of patients with squamous cell lung carcinoma from said test population according to the following criteria: the overall survival of patients with squamous cell lung carcinoma in the dual high expression panel was shorter than that of patients with squamous cell lung carcinoma in the non-dual high expression panel.
Use of TIGIT and CD47 as markers in any one of (a1) - (a6) as follows:
(A1) preparing a product for prognosis evaluation of a squamous cell lung carcinoma patient;
(A2) preparing a product for predicting postoperative risk of a patient with squamous cell lung carcinoma;
(A3) preparing a product for predicting the postoperative overall survival period of the squamous cell lung carcinoma patient;
(A4) assessing prognosis of patients with squamous cell lung carcinoma;
(A5) predicting postoperative risk of the lung squamous carcinoma patient;
(A6) predicting the postoperative overall survival time of the squamous cell lung carcinoma patient.
CN202210452237.8A 2022-04-27 2022-04-27 Lung squamous carcinoma patient prognosis evaluation system based on CD47 and TIGIT double targets and application thereof Pending CN114672567A (en)

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