LU503242B1 - Application of Products for Detecting the Expression Levels of SCN4A and SCN7A mRNA in Preparing Liver Cancer Prognosis Prediction Products - Google Patents

Application of Products for Detecting the Expression Levels of SCN4A and SCN7A mRNA in Preparing Liver Cancer Prognosis Prediction Products Download PDF

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LU503242B1
LU503242B1 LU503242A LU503242A LU503242B1 LU 503242 B1 LU503242 B1 LU 503242B1 LU 503242 A LU503242 A LU 503242A LU 503242 A LU503242 A LU 503242A LU 503242 B1 LU503242 B1 LU 503242B1
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scn7a
scn4a
liver cancer
mrna
survival time
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LU503242A
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French (fr)
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Hongying Zhang
Yan Yan
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Huizhou Municipal Central Hospital
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G01N33/57438—Specifically defined cancers of liver, pancreas or kidney
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

Abstract

The invention discloses the application of products for detecting the expression levels of SCN4A mRNA and/or SCN7A mRNA in preparing the liver cancer prognosis prediction kit. And the invention discloses and finds that the sodium channel coding gene family (SCN family) can be used as a prognostic molecular marker of hepatocellular carcinoma, especially SCN4A and SCN7A, which have a good effect in predicting the prognosis of hepatocellular carcinoma. Among them, SCN7A has a better prognostic value in Asian HCC patients. And regardless of the expression level of mRNA or protein of SCN7A, the higher the expression level of SCN7A, the better the prognosis of liver cancer patients. Even the DNA mutation of SCN7A can distinguish different prognosis of liver cancer patients.

Description

DESCRIPTION LUs03242
Application of Products for Detecting the Expression Levels of SCN4A and
SCN7A mRNA in Preparing Liver Cancer Prognosis Prediction Products
TECHNICAL FIELD
The invention relates to the technical field of prognosis of liver cancer, in particular to the application of products for detecting the expression levels of SCN4A and SCN7A
MRNA in preparing liver cancer prognosis prediction products.
BACKGROUND
At present, the incidence and mortality of cancer are decreasing in the world, but the incidence and mortality of liver cancer are still on the rise in most countries.
Hepatocellular carcinoma (HCC) accounts for the majority of adult hepatocellular carcinoma. In China, liver cancer is the fourth most common cancer. There are many treatments for liver cancer, including surgery, transcatheter arterial chemoembolization (TACE) and radiotherapy. Among all the treatments, surgical treatment is still the first choice for liver cancer. However, surgical indications are limited. Therefore, finding a valuable biomarker can better evaluate the diagnosis and prognosis of HCC patients, and will be helpful to guide the treatment.
At present, the most commonly used serum biomarker for clinical diagnosis of HCC is alpha-fetoprotein (AFP), but it also has its limitations, that is, its specificity and sensitivity are low. In order to improve the specificity and sensitivity of HCC diagnosis, studying the mechanism of HCC occurrence, development and metastasis and identifying new biomarkers are very important. The newly discovered biomarkers of HCC include Golgi glycoprotein 73, glypican 3, transforming growth factor-B1, insulin-like growth factor 2, etc. However, it is still difficult to fully describe HCC with a single biomarker. The molecular characteristics of HCC have not been fully understood, and many new biomarkers still need to be discovered.
Sodium channel is a classic ion channel, which has been proved to play a key role in sensory transmission system in nervous system. According to its special function, marly 203242 clinical medicines have been invented for sodium channel, which is used to manage pain, for example, local anesthesia. The coding gene of sodium channel is SCN family (SCN1A-SCN11A). SCN plays an important role in many pathophysiological processes, including those involving tumors, such as colon, cervical cancer and prostate cancer, and participates in manipulating the proliferation, migration and invasion of cells in vitro and in vivo. However, the prognostic value of SCN family in HCC remains a mystery.
SUMMARY
The purpose of the present invention is to overcome the above shortcomings of the prior technology, and provide the application of products for detecting the expression levels of SCN4A and SCN7A mRNA in preparing liver cancer prognosis prediction products. The present invention discusses the prognosis value of SCN family members through analysis, and provides potential therapeutic targets for this challenging disease.
In order to achieve the above purpose, the present invention is realized by the following schemes:
The first purpose of the present invention is to provide the application of products for detecting the expression levels of SCN4A mRNA and/or SCN7A mRNA in preparing liver cancer prognosis prediction products.
The second purpose of the present invention is to provide the application of products for detecting SCN7A mutation in preparing prognosis prediction products for liver cancer.
The third purpose of the present invention is to provide the application of products for detecting the expression level of SCN7A protein in preparing liver cancer prognosis prediction products.
In order to achieve the above purposes, the present invention is realized by the following schemes:
The inventor found that SCN2A/4A/5A/8A mRNA was highly expressed in tumor tissues, while SCN1A/7A/11A mRNA was low expressed in tumor tissues. The results of
SCN4A and SCN7A were consistent with those of our tissue microarray analysis.
Pan-tumor analysis of TIMER database shows that the expression of SCN7A in tumo}+/508242 decreases steadily. SCN4A and SCN7A are related to tumor grade, lymph node metastasis, histological subtype, patient race, individual tumor stage and TP53 mutation state in different degrees. Kaplan-Meier plotter prognosis analysis shows that high expression of SCN4A mRNA is related to better overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS), and high expression of SCN7A
MRNA is related to better OS. In Asians, higher SCN4A is associated with better OS and
DSS, while high expression of SCN7A is associated with better OS, relapse-free survival (RFS), DSS and PFS. And cBioPortal data analysis shows that SCN7A mutation is related to RFS and PFS. Furthermore, the expression of SCN4A and SCN7A protein in hepatocellular carcinoma is detected by immunohistochemistry, and the survival analysis is made based on the survival data. Univariate survival analysis shows that the high expression of SCN7A protein is significantly associated with better OS and RFS.
Multivariate analysis shows that SCN7A is an independent prognostic factor of OS and
RFS. To sum up, the expression of SCN4A and SCN7A in HCC has significant and stable changes. The expression of SCN7A in hepatocellular carcinoma has better prognostic value.
Therefore, the present invention claims the following contents:
The application of products for detecting the expression levels of SCN4A and/or
SCN7A mRNA in preparing liver cancer prognosis prediction products.
Wherein, SCN4A mRNA and SCN7A mRNA???
Preferably, the prognosis is overall survival time (OS), relapse-free survival time (RFS), disease-specific survival time (DSS) and progression-free survival time (PFS) of liver cancer.
More preferably, one or more of the overall survival times (OS), disease-specific survival time (DSS) and progression-free survival time (PFS) of liver cancer patients with high expression of SCN4A mRNA are better.
Preferably, the overall survival time (OS) of liver cancer patients with high expression of SCN7A mRNA is better.
The application of products for detecting the expression levels of SCN4A and/or
SCN7A mRNA in preparing liver cancer prognosis prediction products. LU503242
Wherein, SCN4A mRNA and SCN7A mRNA???
Preferably, the prognosis is overall survival time (OS), relapse-free survival time (RFS), disease-specific survival time (DSS) and progression-free survival time (PFS) of liver cancer.
More preferably, one or more of the overall survival times (OS), disease-specific survival time (DSS) and progression-free survival time (PFS) of liver cancer patients with high expression of SCN4A mRNA are better.
Preferably, the overall survival time (OS) of liver cancer patients with high expression of SCN7A mRNA is better.
As a specific embodiment, the products for detecting the expression level of SCN4A
MRNA and/or SCN7A mRNA are chips.
And the application of products for detecting SCN7A mutation in preparing prognosis prediction products for liver cancer.
Preferably, the prognosis is one or more of relapse-free survival time (RFS) and progression-free survival time (PFS), and one or more of relapse-free survival time (RFS) and progression-free survival time (PFS) of patients with SCN7A mutant liver cancer are better.
And the application of products for detecting the expression level of SCN7A protein in preparing liver cancer prognosis prediction products.
Wherein, SCN4A protein and SCN7A protein???
Preferably, the prognosis is one or more of the overall survival times (OS) and relapse-free survival time (RFS) of liver cancer, and the higher the expression of SCN7A protein, the better one or more of the overall survival times (OS) and relapse-free survival time (RFS), and the higher the expression, the better the survival rate.
As a specific embodiment, the product for detecting the expression level of SCN7A protein is an immunohistochemical detection reagent for SCN7A protein.
Compared with the prior technology, the invention has the following beneficial effects:
The inventor finds that the sodium channel coding gene family (SCN family) can be used as a prognostic molecular marker of hepatocellular carcinoma, especially SCN4A/503242 and SCN7A, which have a good effect in predicting the prognosis of hepatocellular carcinoma. Among them, SCN7A has a better prognostic value in Asian HCC patients.
And regardless of the expression level of mRNA or protein of SCN7A, the higher the expression level of SCN7A, the better the prognosis of liver cancer patients. Even the
DNA mutation of SCN7A can distinguish different prognosis of liver cancer patients.
BRIEF DESCRIPTION OF THE FIGURES
Fig. 1 shows the mRNA expression of SCN family members in HCC; (A) The expression of SCN1A mRNA in tumor tissues and normal tissues; (B) The expression of
SCN2A mRNA in tumor tissues and normal tissues; (C) The expression of SCN3A mRNA in tumor tissues and normal tissues; (D) The expression of SCN4A mRNA in tumor tissues and normal tissues; (E) The expression of SCN5A mRNA in tumor tissues and normal tissues; (F) The expression of SCN7A mRNA in tumor tissues and normal tissues; (G) The expression of SCN8A mRNA in tumor tissues and normal tissues; (H) The expression of SCN9A mRNA in tumor tissues and normal tissues; (I) The expression of
SCN11A mRNA in tumor tissues and normal tissues; * P < 0.05, ** P < 0.01 and *** P < 0.001.
Fig. 2 is a tissue microarray analysis of hepatocellular carcinoma tissues and matched adjacent tissues; (A) Hierarchical cluster heat map shows that genes with significant changes in expression in HCC tissues and adjacent non-tumor tissues; (B)
The volcano map shows all genes in liver cancer tissues and adjacent non-tumor tissues.
Fig. 3 is a pan-tumor analysis of SCN4A and SCN7A and the relationship between
SCN4A and SCN7A and clinicopathological factors of liver cancer patients. (A)
Pan-tumor analysis of SCN4A; (B) Pan-tumor analysis of SCN7A. (C) The relationship between SCN4A and SCN7A and tumor grade; (D) The relationship between SCN4A/7A and lymph node metastasis; (E) The relationship between SCN4A/7A and tumor tissue types. (F) The relationship SCN4A/7A and the race of patients; (G) The relationship between SCN4A/7A and tumor grade. (H) The relationship between SCN4A/7A and
TP53 mutation. * P < 0.05, ** P < 0.01 and *** P < 0.001. LUs03242
Fig. 4 shows the prognostic significance of Kaplan-Meier plotter analysis of
SCN4A/7A mRNA in HCC patients; (A) The high expression of SCN4A mRNA is related to better OS (P < 0.001), DSS (P = 0.007) and PFS (P= 0.012); (B) The high expression of SCN4A mRNA is related to better OS (P = 0.018).
Fig. 5 shows the prognostic significance of Kaplan-Meier plotter analysis of SCN4A and SCN7A mRNA in Asian HCC patients; (A) The high expression of SCN4A mRNA is related to better OS (P < 0.001) and DSS (P = 0.013); (B) The high expression of SCN7A mRNA is related to better OS (P = 0.004), RFS (P < 0.001), DSS (P = 0.001) and PFS (P < 0.001).
Fig. 6 is cBioPortal's survival analysis of SCN4A and SCN7A mutations in HCC; (A)
SCN4A mutation is not related to OS (p > 0.05), RFS (p > 0.05), DSS (p > 0.05) and PFS (P > 0.05); (B) SCN7A mutation is related to RFS (P = 0.034) and PFS (P < 0.001).
Fig. 7 shows the expression of SCN4A and SCN7A protein in HCC detected by immunohistochemistry, and the prognosis analysis of SCN4A and SCN7A protein expression and patient survival. (A) The expression of SCN4A in hepatocellular carcinoma; (B) The expression of SCN4A protein is not related to RFS (P > 0.05); (C)
The expression of SCN4A protein is not related to OS (P > 0.05); (D) The expression of
SCN/7A in hepatocellular carcinoma; (E) High expression of SCN7A protein is related to longer RFS (P = 0.003); (F) High expression of SCN7A protein is related to longer OS (P = 0.003); (G) Multivariate survival analysis of RFS and OS in hepatocellular carcinoma.
DETAILED DESCRIPTION OF THE INVENTION
The present invention will be further explained in detail with reference to the accompanying figures and specific embodiments, which are only used to explain the present invention, but not to limit the scope of the present invention. Unless otherwise specified, the test methods used in the following embodiments are conventional methods;
Materials and reagents used, unless otherwise specified, are commercially available reagents and materials. 1. Ethical statements and tissue specimens
The following embodiment (Ethics NO.: GZR2017-130) was approved by tH&505242
Clinical Research Ethics Committee of Cancer Center, Sun Yat-sen University, and was carried out according to the principles of the Helsinki Declaration. Most of the data come from online databases.
In the hepatobiliary oncology department of Sun Yat-sen University Cancer Center, 6 pairs of HCC and corresponding adjacent tissues samples and 306 tumor tissue samples were obtained, and each patient's informed consent was obtained. The patient did not receive preoperative treatment and had no history of other malignant tumors.
Patients with extrahepatic metastasis and hepatocellular carcinoma invading biliary system were excluded. Postoperative pathological results were all hepatocellular carcinoma. There are two ways of recurrence: intrahepatic and extrahepatic. 2. UALCAN
UALCAN is a cancer data analysis website based on The Cancer Genome Atlas (TCGA) database. It helps medical researchers to analyze the gene transcription differences between tumors and normal samples, and then make more thorough analysis, such as identification and survival analysis of the biomarkers when the target gene is found. In addition, related information in other databases can be queried through related links. 3. TIMER
Timer (http://timer.cistrome.org/) is an analysis website containing resources of various cancer types. 4. Kaplan-Meier plotter
Kaplan-Meier plotter is one of the largest tumor data sets, containing 54,000 genes related to the survival of various cancers. 5. Data analysis
All data were analyzed by GraphPad Software 6 (GraphPad, La Jolla, CA, USA) and
Statistical Package for the Social Sciences (SPSS, Version 22.0). Kaplan-Meier method was used to evaluate the relationship between SCN4A or SCN7A expression and survival prognosis. Chi-square test was used to verify the correlation between clinicopathological factors and the expression of SCN4A or SCN7A, and Cox proportional hazard regression model was used to evaluate prognostic factors 7503242 univariate and multivariate analysis. P < 0.05 is statistically significant.
Embodiment 1 Expression difference of different SCN family members in HCC patients
Firstly, the mRNA expression of different SCN members in normal tissues and primary tumors 1 Experimental method
The mRNA expression of different SCN members in normal tissues and primary tumors was analyzed by using UALCAN database. 2. Experimental results
The expression levels of nine members of SCN family were analyzed, and the results are shown in Fig. 1. The results show that SCN4A/5A/8A is highly expressed in tumor tissues, while SCN1A/2A/7A/11A is poorly expressed in tumor tissues.
Secondly, the expression of SCN family members in tumor tissues and adjacent non-tumor tissues of liver cancer patients was detected by chip analysis. 1. Experimental methods
The expression of SCN family members in tumor tissues and adjacent non-tumor tissues of 6 pairs of liver cancer patients was detected by chip analysis. Tissue chip analysis was undertaken by Kangcheng Bio. 2. Experimental results
As shown in Fig. 2, only the expression of SCN4A (P = 0.049) and SCN7A (P = 0.011) changed significantly; In addition, the expression trend of SCN4A and SCN7A in tumor tissues and non-tumor tissues is consistent with the results of UALCAN database, that is, the expression of SCN4A in tumor is higher, while that of SCN7A is lower.
Embodiment 2 Pan-tumor analysis of SCN4A and SCN7A . Experimental Methods
Pan-tumor analysis of SCN4A and SCN7A was carried out in TIMER database. The
MRNA expressions of SCN4A and SCN7A in 38 kinds of tumor tissues were detected and compared with those in normal tissues. 2. The experimental results
As shown in Figs. 3A and B, SCN4A is highly expressed in several cancers, such 43/003242 liver cancer; However, its expression is low in some types of tumor tissues. However, the expression of SCN7A is stably down-regulated in many types of tumors, including liver cancer.
Embodiment 3 Relationship between SCN4A and SCN7A and clinicopathological factors of HCC patients 1. Experimental Methods
The relationship between SCN4A/7A and pathological factors, such as tumor grade, lymph node metastasis, histological subtype, patient race, individual tumor stage and
TP53 mutation, was analyzed by UALCAN database. 2. The experimental results
As shown in Fig. 3C, the mRNA expression of SCN4A increased significantly in all grades, while the expression of SCN7A decreased gradually with the increase of tumor grade, and changed significantly in grade 1 and grade 3. The MRNA expression levels of
SCN4A and SCN7A were also significantly related to the tumor stages. Similarly, SCN4A was highly expressed in all stages, while SCN7A decreased in stages 3 and 4 (Fig. 3G).
The expression of SCNAA in the tissues with lymph node metastasis was higher than that in the tissues without lymph node metastasis. In terms of histological subtype, compared with normal tissues, the expression of SCN4A and SCN7A was significantly different only in hepatobiliary carcinoma (Fig.3E). From the results shown in Fig. 1F, it is found that only the tumor samples of Caucasian or Asian patients have high expression of SCN4A, while the tumor samples of African or Asian patients have low expression of
SCN7A. The expression level of SCN4A was higher in both TP53 mutant group and
TP53 non-mutant group, while the expression of SCN7A was significantly decreased only in TP53 mutant group (Fig. 3H).
Embodiment 4 Prognostic significance of SCN4A and SCN7A in HCC 1. Experimental Methods
Kaplan-Meier plotter was used to analyze the relationship between the expressions of SCN4A and SCN7A and the overall survival (OS), relapse-free survival (RFS), disease-specific survival (DSS) and progression-free survival (PFS) of hepatocellular carcinoma. LU503242
The relationship between SCN4A and SCN7A gene mutations and OS, RFS, DSS or PFS in HCC patients was detected by cBioPortal database. 2. The experimental results
The high expression of SCN4A mRNA was related to better OS, DSS and PFS (Fig. 4A), while the high expression of SCN7A mRNA was related to better OS (Fig. 4B).
However, in Asian patients, the high expression of SCN4A mRNA is related to better
OS and DSS (Fig. SA), and the high expression of SCN7A mRNA is related to better OS,
RFS, DSS and PFS (Fig. 5B).
SCN4A mutation is not related to OS, RFS, DSS and PFS (Fig. GA), but SCN7A mutation is related to RFS and PFS (Fig. 6B).
Embodiment 5 Expression and prognostic value of SCN4A and SCN7A proteins in
HCC tissues 1. Experimental Methods
Immunohistochemical analysis was performed on 306 tumor tissue samples. The specific methods were as follows:
Hepatocellular carcinoma tissue was rehydrated with alcohol gradient, and peroxidase was blocked by H2O2. Then, the antigen was repaired by microwave heating in citric acid buffer (pH 6.0). Next, the tissue was incubated with the primary antibody at 4°C overnight. After incubation with the second antibody, the color was developed by
DAB.
Glass slides were divided into four groups (Chen, D.T., J.H. Pan, Y.H. Chen, W. Xing,
Y. Yan, Y.F. Yuan, et al., and the mu-opioid receptor is a molecular marker for poor prognosis in hepatocellular carcinoma and represents a potential therapeutic target. Br J
Anaesth, 2019.122 (6): p. e157-e167 DOI: 10.1016/j.bja.2018.09.030.): And the grading standard of dyeing intensity is: 0 = no staining, 1 = weak staining, 2 = medium staining and 3 = strong staining.
The grading standard of positive percentage of tumor is: 0 (0-10%), 1 (10%-25%), 2 (26%-50%), 3 (51%-75%) and 4 (75%-100%).
Multiply the two scores and divide them into four groups of immunohistochemistry:
missing staining (-) (score 0 ~ 3), weak staining (+) (score 4 ~ 6), medium staining (++j7803242 (score 7 - 9) and strong staining (+++) (score 10 ~ 12). 2. The experimental results
According to the immunohistochemical results, four different staining intensities were grouped (Figs. 7A and 7D). 306 patients with an average age of 50.7 years (ranging from 20 to 83), including 270 males and 36 females, were followed up for a median of 59.1 months (ranging from 1 to 129). As shown in Figs. 7B and 7C, the expression of SCN4A protein is not related to OS or RFS; However, the expression of
SCN/7A protein is significantly related to OS (P = 0.001) and RFS (P = 0.003) (Figs. 7E and 7F), and the higher the expression, the better the survival rate, which is consistent with the results of online database.
The multivariate analysis of the expression of SCN7A and patient's age, tumor size, adjacent organ invasion, ICGI15, tumor grade, TNM grade is shown in Table 1 that????
Table 1 Univariate survival analysis:
RFS rate Os rate
Variables Cases (%) P (%) P value — value —— 3y Sy 3y Sy
Gender
Female 36 82.3 72.1 79.3 715
Male 270 654 576 0121 86.1 721 0.321
Age (y) <50 150 64.1 57.1 80.0 75.0 > 50 156 705 612 0283 801 687 0.397
HbsAg
Negative 42 745 68.7 786 70.5
Positive 264 66.3 57.7 0147 80.3 720 0.944
Child-Pugh classification!
A 302 67.7 594 80.5 72.0
B 4 500 500 0079 500 500 0.166
Alpha-fetoprotein (AFP, ng/ml) LUS03242 <20 135 654 56.9 87.4 813 20-400 69 71.0 63.1 739 61.7 > 400 102 68.0 603 0767 745 659 0.038
Gamma glutamyl transferase (GGT, units/L) <50 184 75.7 66.3 826 792 > 50 122 545 481 0.002 762 604 0.003
Tumor size (cm) <5 161 749 653 85.1 78.0 >5 145 586 521 0.009 745 645 0.061
Satellite nodule
No 264 719 63.8 83.3 75.0 <
Yes 42 36.0 21.0 595 50.4 < 0.001 0.001
Tumor capsule
No 114 66.1 59.6 77.2 70.2
Yes 192 68.1 589 0659 81.8 727 0.601
Vascular invasion
No 252 69.1 59.8 82.9 747
Yes 54 588 588 0326 66.7 56.7 0.004
Ascites
No 284 68.3 60.0 80.3 72.0
Yes 22 539 485 0379 773 675 0.481
Tumor counts 1 251 705 632 83.7 75.2 >1 55 518 352 0.002 636 553 <0.001 (Continued)
RFS rate P Os rate
Variables Cases P value (%) value (%)
3y Sy 3y Sy LU503242
Adjacent organ invasion
No 257 68.3 60.2 82.1 74.7
Yes 49 629 538 0485 694 556 0.061
HCV-IgG
No 302 67.4 595 80.1 72.1
Yes 4 66.7 333 0478 50.0 500 0.022
Aspartate aminotransferase (AST, units/L) <40 198 729 652 808 76.2 > 40 108 572 478 0.004 787 63.0 0.068
Alanine aminotransferase (ALT, units/L) <40 184 735 67.3 83.7 76.9 > 40 122 588 475 0.004 750 645 0.007
Total bilirubin (umol/L) < 17.1 217 688 61.0 797 71.4 > 17.1 89 638 549 0538 809 722 0.829
Direct bilirubin (umol/L) <6.9 245 67.8 60.0 816 73.0 >6.9 61 651 556 0736 73.8 665 0.188
Albumin (g/L) <35 8 83.3 444 75.0 40.0 > 35 298 669 594 0938 802 726 0.045
Tumor grade 1/1 230 71.3 61.1 83.5 750 m/v 76 55.3 537 0.063 69.7 61.8 0.005
Cirrhosis
No 79 715 650 79.7 73.6
Yes 227 659 570 0249 800 712 0418
TNM? classification 1/1 241 724 646 79.7 73.6 es LU503242 m/v 65 475 36.4 80.2 71.3 < 0.001 0.001
SCN4A expression
Negative 128 69.9 60.8 79.7 731
Positive 178 656 579 0333 80.3 708 0.903
SCN7A expression
Negative 186 60.5 52.7 75.3 63.4
Positive 120 776 69.0 0.003 875 844 0.001
There is no child-pugh grade C patient; Tumor-lymph node metastasis (TNM) staging was evaluated according to the 7th edition of American Joint Committee on
Cancer (AJCC); Abbreviation: DRD1 dopamine receptor D1; Hepatocellular carcinoma;
AFP y- glutamyltransferase; TNM, tumor-lymph node-metastasis.
The multivariate analysis of SCN7A expression and patient's age, tumor size, adjacent organ invasion, ICGI15, tumor grade and TNM grade is shown in Table 2:
SCN7A (P = 0.034), satellite nodules (P = 0.032) and ALT (P = 0.001) are independent prognostic factors of RFS. In addition, SCN7A (P = 0.025), albumin (P = 0.020) and TNM classification (P = 0.029) are also independent prognostic factors of OS (Fig. 7G and
Table 3).
Table 2 Analysis of correlation between expression of SCN7A and clinicopathological factors in liver cancer patients
SCN7A protein
Characteristic Case —M8M8M8M8Mm
Low s s . High expression P Value expression
Gender
Female 36 18 (50.0%) 18 (50.0%)
Male 270 168 (62.2%) 102 (37.8%) 0.158
Age (y) < 50 150 45 (30.0%) 105 (70.0%) > 50 156 141 (90.4%) 15 (9.6%) < 0.001
HbsAg
Negative 42 29 (69.0%) 13 (31.0%) LUS03242
Positive 264 157 (59.5%) 107 (40.5%) 0.238
Child-Pugh classification!
A 302 183 (60.6%) 119 (39.4%)
B 4 3(75.0%) 1 (25.0%) 0.558
Alpha-fetoprotein (AFP, ng/ml) <20 135 92 (68.1%) 43 (31.9%) 20-400 69 37 (53.6%) 32 (46.4%) > 400 102 57 (55.9%) 45 (44.1%) 0.061
Gamma glutamyl transferase (GGT, units/L) <50 184 106 (57.6%) 78 (42.4%) > 50 122 80 (65.6%) 42 (34.4%) 0.162
Tumor size (cm) <5 161 84 (52.2%) 77 (47.8%) >5 145 102 (70.3%) 43 (29.7%) 0.001
Satellite nodule
No 264 154 (58.3%) 110 (41.7%)
Yes 42 32 (76.2%) 10 (23.8%) 0.028
Tumor capsule
No 114 75 (65.8%) 39 (34.2%)
Yes 192 111(57.8%) 81 (42.2%) 0.167
Vascular invasion
No 252 151 (59.9%) 101 (40.1%)
Yes 54 35 (64.8%) 19 (35.2%) 0.504
Ascites
No 284 174 (60.9%) 111 (39.1%)
Yes 22 13 (59.1%) 9 (40.9%) 0.866
Tumor counts LUs03242 1 251 147 (58.6%) 104 (41.4%) > 1 55 39 (70.9%) 16 (29.1%) 0.089
Adjacent organ invasion
No 257 149 (58.0%) 108 (42.0%)
Yes 49 37 (75.5%) 12 (24.5%) 0.021
HCV-IgG
No 302 182 (60.3%) 120 (39.7%)
Yes 4 4 (100.0%) 0 (0%) 0.106
Aspartate aminotransferase (AST, units/L) <40 198 113 (57.1%) 85 (42.9%) > 40 108 73 (67.6%) 35 (32.4%) 0.072
Alanine aminotransferase (ALT, units/L) <40 178 111 (62.4%) 67 (37.6%) > 40 128 75 (58.6%) 53 (41.4%) 0.506
Total bilirubin (umol/L) <17.1 217 139 (64.1%) 78 (35.9%) > 17.1 89 47 (52.8%) 42 (47.2%) 0.067
Direct bilirubin (umol/L) <6.9 245 151 (61.6%) 94 (38.4%) >6.9 61 35 (57.4%) 26 (42.6%) 0.542
Albumin (g/L) <35 8 4 (50.0%) 4 (50.0%) > 35 298 182 (61.1%) 116 (38.9%) 0.527
Tumor grade 1/1 230 132 (57.4%) 98 (42.6%) m/v 76 54 (71.1%) 22 (28.9%) 0.034
Cirrhosis
No 79 48 (60.8%) 31 (39.2%)
Yes 227 138 (60.8%) 89 (39.2%) 0.996
TNM classification LU503242 1/1 241 127 (52.7%) 114 (47.3%) m/v 65 59 (90.8%) 6 (9.2%) < 0.001
The values with statistical significant are shown in bold; There is no child-pugh class
C patients.
Table 3 Multivariate survival analysis
Hazard ratio
Variables B SE P value (95% CI)
RFS
GGT 0.289 0.202 1.335 (0.899-1.983) 0.152
Tumor size 0.065 0.220 1.067 (0.693-1.641) 0.769
Satellite nodule 1.082 0.505 2.951 (1.098-7.934) 0.032
Tumor counts -0.344 0.472 0.709 (0.281-1.787) 0.466
AST 0.138 0.230 1.148 (0.731~1.802) 0.549
ALT 0.300 0.226 0.469 (0.299~0.735) 0.001
TNM classification 0.176 0.278 1.192 (0.692~2.053) 0.527
SCN7A -0.445 0.210 0.641 (0.425~0.967) 0.034
Os
AFP 0.227 0.131 1.255 (0.971-1.622) 0.083
GGT 0.399 0.227 1.490 (0.955-2.326) 0.079
Satellite nodule -0.067 0.505 0.936 (0.348-2.516) 0.895
Vascular invasion 0.168 0.286 1.182 (0.675-2.072) 0.558
Tumor counts 0.537 0.450 1.711 (0.708~4.133) 0.233 3.018
HCV-lgG 1.105 0.619 0.075 (0.896-10.159)
ALT 0.276 0.230 1.318 (0.839-2.069) 0.231
Albumin -1.146 0.494 0.318 (0.121-0.837) 0.020
Tumor grade -0.041 0.252 0.960 (0.587~1.572) 0.872
TNM classification 0.636 0.291 1.890 (1.068~3.345) 0.029
SCN7A -0.595 0.266 0.552 (0.328~0.929) 0.025
This table only shows the factors that significantly affect RFS or OS. LU503242
Finally, it should be noted that the above embodiments are only used to illustrate the technical schemes of the present invention, but not to limit the scope of protection of the present invention. For those of ordinary skill in the field, other different forms of changes or variations can be made on the basis of the above descriptions and ideas, and it is not necessary and impossible to exhaustive all the embodiments here. Any modification, equivalent substitution and improvement made within the spirit and principle of the present invention shall be included in the scope of protection of the claims of the present invention.

Claims (10)

1. The application of products for detecting the expression levels of SCN4A and/or SCN7A mRNA in preparing liver cancer prognosis prediction products.
2. The application according to claim 1 is characterized in that the prognosis is overall survival time, relapse-free survival time, disease-specific survival time and progression-free survival time of liver cancer.
3. The application according to claim 2 is characterized in that one or more of the overall survival time, disease-specific survival time and progression-free survival time of liver cancer patients with high expression of SCN4A mRNA are better.
4. The application according to claim 2 is characterized in that the overall survival time of liver cancer patients with high expression of SCN7A mRNA is better.
5. The application according to claim 2 is characterized in that the liver cancer patients are Asian, and one or more of the overall survival time and disease-specific survival time of liver cancer patients with high expression of SCN4A mRNA are better.
6. The application according to claim 2 is characterized in that the liver cancer patients are of Asian, and one or more of the overall survival time, relapse-free survival time, disease-specific survival time and progression-free survival time (PFS) of liver cancer patients with high expression of SCN7A mRNA are better.
7. The application of products for detecting SCN7A mutation in preparing prognosis prediction products for liver cancer.
8. The application according to claim 7 is characterized in that the prognosis is one or more of relapse-free survival time and progression-free survival time, and one or more of relapse-free survival time and progression-free survival time of patients with SCN7A mutant liver cancer are better.
9. The application of products for detecting the expression level of SCN7A protein in preparing liver cancer prognosis prediction products.
10. The application according to claim 9 is characterized in that the prognosis is one or more of the overall survival time and relapse-free survival time of liver cancer, and the higher the expression of SCN7A protein, the better one or more of the overall survival time and relapse-free survival time.
LU503242
LU503242A 2022-12-22 2022-12-22 Application of Products for Detecting the Expression Levels of SCN4A and SCN7A mRNA in Preparing Liver Cancer Prognosis Prediction Products LU503242B1 (en)

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