CN113943802A

CN113943802A - Application of GOLT1B in prognosis of renal cancer

Info

Publication number: CN113943802A
Application number: CN202111192383.3A
Authority: CN
Inventors: 戴勇; 张巍; 汤冬娥; 徐勇; 蔡晚霞
Original assignee: Individual
Current assignee: Individual
Priority date: 2021-10-13
Filing date: 2021-10-13
Publication date: 2022-01-18

Abstract

The invention discloses application of GOLT1B in diagnosis and prognosis of kidney cancer. In a first aspect of the present invention, there is provided the use of a reagent for quantitatively detecting GOLT1B in the preparation of a kit for the diagnosis and/or prognosis of renal cancer. According to the application of the embodiment of the application, at least the following beneficial effects are achieved: the gene differentially expressed in kidney cancer and normal kidney tissue or the protein thereof is screened by a series of bioinformatics analysis methods, and the GOLT1B gene or the GOLT1B protein is provided for the first time as a biomarker for diagnosing kidney cancer or judging the prognosis of the kidney cancer, so that the defect of the conventional kidney cancer diagnosis index is overcome, and the clinical diagnosis value is good.

Description

Application of GOLT1B in prognosis of renal cancer

Technical Field

The application relates to the technical field of kidney cancer diagnosis, in particular to application of GOLT1B in prognosis of kidney cancer.

Background

Renal cancer is one of the most common malignant tumors of the urinary system, and the most common of the renal cancers is renal cell carcinoma, which accounts for about 90% of renal cancers. Renal cell carcinoma can be classified into clear cell carcinoma of kidney, papillary cell carcinoma of kidney, and renal chromophobe cell carcinoma according to the histopathology. In recent years, the incidence of renal cell carcinoma has increased year by year, and renal cancer is not easily diagnosed at an early stage, and metastasis has occurred in about 30% of patients when they present clinical symptoms. On the other hand, a large part of patients with early renal cancer still have recurrent metastasis finally after operation, and the 5-year survival rate of the patients is low. However, there is no clinically ideal molecular index to assess risk of prognosis at present. Therefore, there is a need to find an effective prognostic biomarker so as to assist clinical practice selection, guide the patient review cycle, and realize early discovery and early treatment of tumor progression.

Disclosure of Invention

The present application is directed to solving at least one of the problems in the prior art. Therefore, the application provides a renal cancer marker with good prognostic value, and the reagent for quantitatively detecting the marker can be used for prognosis judgment of renal cancer.

In a first aspect of the present application, there is provided the use of a reagent for the quantitative detection of GOLT1B in the preparation of a kit for the prognosis of renal cancer.

According to the application of the embodiment of the application, at least the following beneficial effects are achieved:

the application screens differentially expressed genes or proteins thereof in kidney cancer and normal kidney tissues by a series of bioinformatics analysis methods, firstly provides GOLT1B gene or GOLT1B protein as a biomarker for judging the prognosis of kidney cancer, makes up the defects of the related indexes of the existing kidney cancer, and has good clinical value.

Among them, GOLT1B (Golgi Transport 1B, Gene ID: 51026) is a Golgi transporter 1B Gene, which is a protein-coding Gene, and diseases related to GOLT1B are currently known to include cervical adenosquamous carcinoma and cervical dystrophy. The Gene Ontology (GO) annotation associated with this gene includes outdated signal transduction activity and lipase activity, while an important paralogue of this gene is GOLT 1A. The diagnosis of kidney cancer refers to the judgment of whether a subject suffers from kidney cancer, and the prognosis of kidney cancer refers to the prediction of the possible future course and outcome of the subject, including but not limited to the risk of different processes or outcomes of recurrence, metastasis, death, etc. of kidney cancer.

In some embodiments of the present application, the agent quantitatively detects the marker at the gene level or at the protein level. The reagent for quantitatively detecting nucleic acid at the gene level is carried out by methods including, but not limited to, Polymerase Chain Reaction (PCR), isothermal amplification reaction (such as loop-mediated isothermal amplification (LAMP), Recombinase Polymerase Amplification (RPA) and the like), probe hybridization technique, northern blotting and the like. The reagent for quantitatively detecting GOLT1B protein at the protein level is carried out by the following methods, including but not limited to enzyme linked immunosorbent assay (ELISA), radioimmunoassay (IRA), immunohistochemical staining, western blotting, electrophoresis, liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) and the like.

In some embodiments of the present application, the reagent for quantitatively detecting a marker at the gene level is selected from the group consisting of a primer, a probe, and a gene chip. The primer is a primer capable of specifically amplifying a GOLT1B gene, the probe is a probe capable of specifically recognizing a GOLT1B gene or a transcript of the gene, and the gene chip is a composite structure formed by an array of the probes fixed on a substrate material (specifically including but not limited to a polymer such as a nylon membrane, a nitrocellulose membrane, glass and the like).

In some embodiments of the present application, the reagent that quantitatively detects the marker at the protein level is an antibody. The antibody is an antibody capable of specifically recognizing GOLT1B protein, and specifically includes at least one of monoclonal antibody and polyclonal antibody.

In some embodiments of the present application, the renal cancer is renal cell carcinoma, which may be further classified as renal chromophobe carcinoma (KIRC), renal clear cell carcinoma (KIRC), renal papillary cell carcinoma (KIRP). In the examples of the application, the expression of the above three renal cell carcinomas in GOLT1B is obviously increased compared with the expression in normal tissues or tissues beside the cancer, so the prognosis of renal cancer can be judged by judging whether the expression level of the subject GOLT1B is higher than a set threshold value; if the value is lower than the threshold value, judging that the prognosis of the patient with the kidney cancer is better; and above the threshold, the prognosis of renal cancer is judged to be poor. The set threshold value can be obtained by comprehensive calculation according to the expression data of GOLT1B in a specific renal cancer patient database, or by comprehensive calculation after detection of specific clinical experiment samples.

In some embodiments of the present application, the prognostic judgment includes predicting survival or survival of the subject. Wherein, the survival period is a judgment on how long the survivor of the testee can be kept according to the illness condition, physical condition and the like of the testee. And survival rate is the probability of survival under a specific time node. In general, survival can be divided into overall survival, median survival, progression-free survival, and the like. In the examples of the present application, the applicant found that the expression of GOLT1B in renal cancer patients is closely related to their survival, and thus the survival of the subjects can be predicted based on the expression level of GOLT 1B.

In some embodiments of the present application, the survival is at least one of overall survival, relapse-free survival, progression-free survival. Overall survival (OA) refers to the time from the confirmation of kidney cancer to death due to any cause. Recurrence-free survival (RFS) refers to the time from initial surgery to the earliest evidence of recurrence. Progression-free survival (PFS) refers to the time from randomization to the first onset of disease progression, or death of any cause, wherein disease progression refers to tumor growth, metastasis of primary tumor lesions, discovery of new lesions, etc. In the examples of the present application, applicants found that there is a significant correlation between the expression level of GOLT1B in the subject and the overall survival rate of the subject, etc., and thus the survival of the subject can be predicted by the expression level of GOLT 1B.

In some embodiments of the present application, the survival rate comprises at least one of an annual survival rate, a two-year survival rate, a three-year survival rate, a five-year survival rate, a ten-year survival rate.

Additional aspects and advantages of the present application will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the present application.

Drawings

FIG. 1 is the results of differential expression of GOLT1B between KICH patients and normal persons in example 1 of the present application.

FIG. 2 is the results of differential expression of GOLT1B between KIRC patients and normal persons in example 1 of the present application.

FIG. 3 is the results of differential expression of GOLT1B between KIRP patients and normal persons in example 1 of the present application.

Fig. 4 is a survival curve for KICH patients with different levels of gold 1B expression in example 1 of the present application.

Fig. 5 is a survival curve for KIRC patients with different levels of gold 1B expression in example 1 of the present application.

FIG. 6 is a survival curve for KIRP patients with different expression levels of GOLT1B in example 1 of the present application.

FIG. 7 is a forest map of the overall survival of renal cancer patients analyzed by the single factor cox regression model in example 1 of the present application.

Detailed Description

The conception and the resulting technical effects of the present application will be clearly and completely described below in conjunction with the embodiments to fully understand the objects, features and effects of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, and not all embodiments, and other embodiments obtained by those skilled in the art without inventive efforts based on the embodiments of the present application belong to the protection scope of the present application.

The following detailed description of embodiments of the present application is provided for the purpose of illustration only and is not intended to be construed as a limitation of the application.

In the description of the present application, the meaning of a plurality is one or more, the meaning of a plurality is two or more, and the above, below, exceeding, etc. are understood as excluding the present number, and the above, below, within, etc. are understood as including the present number. If the first and second are described for the purpose of distinguishing technical features, they are not to be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated or implicitly indicating the precedence of the technical features indicated.

In the description of the present application, reference to the description of the terms "one embodiment," "some embodiments," "an illustrative embodiment," "an example," "a specific example," or "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present application. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

Example 1

The differential expression data of GOLT1B in kidney cancer and Normal kidney tissue are searched in TCGA library and analyzed, the results are shown in fig. 1-3, wherein fig. 1-3 are respectively the results of contrast between KICH, KIRC and KIRP patients and Normal persons, in the figure, the abscissa Tumor is kidney cancer patient, Normal is Normal human tissue or tissues beside cancer, and the ordinate is normalized (+0.001) and logarithmized value of Transcripts Per Million (TPM). As can be seen from the figure, gilt 1B expression was significantly increased in KIRC and KIRP compared to normal or paracancerous tissues.

Further using RNA-Seq data in TCGA database and patient survival time information to analyze the prognosis value of GOLT1B in renal cancer patients, calculating survival curve by Kaplan-Meier method, and testing statistical significance of logrank. As shown in fig. 4 to 6, the abscissa of the graph is the number of days, the ordinate is the overall survival rate, the upper graph is low expression, the lower graph is high expression, and the number of risk persons (number at risk) at different time points is below the graph. As can be seen from the figure, there are significant differences in all three groups of results. The lower the expression level of GOLT1B, the higher the overall survival rate or overall production time of renal cancer patients.

Differential expression data of GOLT1B of renal cancer patients (including KICH, KIRC and KIRP) and other clinical information are confirmed from a TCGA database, the relation between different variables such as age, sex, stage and GOLT1B expression of the renal cancer patients and the overall life cycle is analyzed through a single-factor regression model, and the result is a forest map of the single-factor cox regression analysis of the overall life cycle as shown in FIG. 7, wherein pM _ stage refers to grouping of tumors according to the remote metastasis condition, and pTNM _ stage refers to the stage condition of the tumors according to the comprehensive range and size (T) of primary tumors and the lymph node dissemination condition and the remote metastasis condition. As can be seen from the figure, the expression level of gilt 1B was significantly correlated with overall survival (p values were all less than 0.0001), and thus could be an independent prognostic factor.

From the above results, it can be seen that GOLT1B can be used as an independent diagnosis or prognosis factor for renal cancer patients, and has a good value for diagnosis or prognosis judgment. It will be appreciated that GOLT1B may also be used in combination with other markers to further improve the accuracy or sensitivity of diagnosis or prognosis of renal cancer.

The present application has been described in detail with reference to the embodiments, but the present application is not limited to the embodiments described above, and various changes can be made within the knowledge of those skilled in the art without departing from the gist of the present application. Furthermore, the embodiments and features of the embodiments of the present application may be combined with each other without conflict.

Claims

1. Application of a reagent for quantitatively detecting GOLT1B in preparation of a kit for prognosis of kidney cancer.

2. The use of claim 1, wherein the agent quantitatively detects the marker at the gene level or at the protein level.

3. The use according to claim 2, wherein said reagents for quantitative detection of said markers at the gene level are selected from the group consisting of primers, probes and gene chips.

4. The use according to claim 2, wherein said reagent for quantitatively detecting said marker at the protein level is an antibody.

5. The use according to claim 1, wherein the kidney cancer is any one of renal chromophobe cancer, renal clear cell cancer, renal papillary cell cancer.

6. The use of claim 1, wherein the prognosis comprises predicting survival or survival of the subject.

7. The use of claim 6, wherein the survival is at least one of overall survival, recurrence-free survival, progression-free survival.

8. The use of claim 6, wherein the survival rate comprises at least one of annual survival rate, two-year survival rate, three-year survival rate, five-year survival rate, and ten-year survival rate.