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pmid:34327857

A MUCINs expression signature impacts overall survival in patients with clear cell renal cell carcinoma.

Hui Meng · Xuewen Jiang · Huangwei Huang · Neng Shen · Changsheng Guo · Chunxiao Yu · Gang Yin · Yu Wang

Cancer medicine · 2021 doi:10.1002/cam4.4128

Paper

complete

Experiment

complete

Data

partial

Analysis

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pmid:34327857
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2026-11-01T15:41:45Z
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title
A MUCINs expression signature impacts overall survival in patients with clear cell renal cell carcinoma.
doi
10.1002/cam4.4128
pmid
34327857
authors array · 8 items
[0]
Hui Meng
[1]
Xuewen Jiang
[2]
Huangwei Huang
[3]
Neng Shen
[4]
Changsheng Guo
[5]
Chunxiao Yu
[6]
Gang Yin
[7]
Yu Wang
journal
Cancer medicine
year
2021
abstract
BACKGROUND: Kidney cancer, especially clear cell renal cell carcinoma (ccRCC), is one of the most common cancers in the urinary system. Previous studies suggested that certain members of MUCINs could serve as independent predictors for the survival of ccRCC patients. None of them, however, is robust enough to predict prognosis accurately. OBJECTIVE: To analyze the correlation of MUCINs alterations and their expression levels with the prognosis of ccRCC patients and develop a prognosis-related predictor. METHODS: We applied whole-exome sequencing in samples from 22 Chinese ccRCC patients to identify genetic alterations in MUCIN genes and analyzed their genetic alterations, expression, and correlation with survival using the TCGA, GSE73731, and GSE29069 datasets. RESULT: Genetic alternations in MUCINs were identified in 91% and 51% of ccRCC patients in our cohort and the TCGA database, respectively. No correlation with survival was found for the genetic alterations. Using unsupervised clustering analysis of gene expression, we identified two major clusters of MUCIN expression patterns. Cluster 1 was characterized by a global overexpression of MUC1, MUC12, MUC13, MUC16, and OVGP1; and cluster 2 was characterized by a global overexpression of MUC4, MUC5B, MUC6, MUC20, EMCN, and MCAM. Patients with cluster 1 expression pattern had significantly shorter overall survival time and worse clinical features, including higher tumor grades and metastasis. Meanwhile, they had a higher level of mutation counts and more infiltrated immune cells, but lower enrichment in angiogenesis signature genes. A five-MUCINs expression signature was constructed from cluster 1, and notably, it was demonstrated to be associated with shorter overall survival. A similar worse clinical feature, lower angiogenesis but the more immune signature, was identified in samples presented with signature 1. In the validation data set GSE29069, patients with signature 1 were also associated with a trend of poor survival outcomes. CONCLUSION: We established a five-MUCINs expression signature as a new prognostic marker for ccRCC. The distinct tumor microenvironment feature between the two signatures may further affect ccRCC patients' clinical management.
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Kaplan–Meier survival curves and Cox survival analysis were generated by the “survival” package and “survminer” package in R. The Cox proportional hazard ratio and the 95% confidence interval were included in the survival plot. A log‐rank test was used to evaluate the survival curves between different groups.
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Kaplan–Meier survival curves and Cox survival analysis were generated by the “survival” package and “survminer” package in R.
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sections[6] "Survival analysis" paragraph 2
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The Cox proportional hazard ratio and the 95% confidence interval were included in the survival plot.
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sections[9] "Statistical analysis" paragraph 2
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A log‐rank test was used to evaluate the survival curves between different groups.
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The raw sequencing data files were deposited in the Chinese National Genomics Data Center(https://bigd.big.ac.cn/). Left biospecimens may be shared for academic research under prior approval from the government of China.
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The raw sequencing data files were deposited in the Chinese National Genomics Data Center(https://bigd.big.ac.cn/). Left biospecimens may be shared for academic research under prior approval from the government of China.
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Global DNA Hypomethylation Coupled to Repressive Chromatin Domain Formation and Gene Silencing in Breast Cancer
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Clear cell renal cell carcinoma (ccRCC) samples
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Positive correlation of Mucin gene expression in ccRCC‐TCGA
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Correlation of MUCINS expression levels in CCRCC
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Positive correlation of Mucin gene expression in ccRCC‐TCGA
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Negative correlation of Mucin gene expression in ccRCC‐TCGA
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section_index
14
section_title
Correlation of MUCINS expression levels in CCRCC
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TABLE 2
caption
Negative correlation of Mucin gene expression in ccRCC‐TCGA
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[0] array · 4 items
[0]
Mucins
[1]
Mucins
[2]
Pearson r
[3]
p
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[0]
EMCN
[1]
MUC12
[2]
−0.37185
[3]
0
[2] array · 4 items
[0]
EMCN
[1]
MUC13
[2]
−0.34702
[3]
0
[3] array · 4 items
[0]
MUC20
[1]
MUC13
[2]
−0.23436
[3]
4.26E−08
[4] array · 4 items
[0]
EMCN
[1]
OVGP1
[2]
−0.2261
[3]
1.28E−07
[5] array · 4 items
[0]
MCAM
[1]
OVGP1
[2]
−0.21355
[3]
6.33E−07
[6] array · 4 items
[0]
MUC13
[1]
MUC4
[2]
−0.21301
[3]
6.77E−07
[7] array · 4 items
[0]
EMCN
[1]
MUC1
[2]
−0.18511
[3]
1.67E−05
[8] array · 4 items
[0]
MUC4
[1]
MUC1
[2]
−0.15292
[3]
0.000391
[9] array · 4 items
[0]
MUC20
[1]
MUC12
[2]
−0.15079
[3]
0.000472
[10] array · 4 items
[0]
EMCN
[1]
MUC16
[2]
−0.14453
[3]
0.000809
[11] array · 4 items
[0]
EMCN
[1]
MUC5B
[2]
−0.10878
[3]
0.011892
[12] array · 4 items
[0]
MUC12
[1]
MUC4
[2]
−0.08943
[3]
0.038836
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section[14]/table-wrap[2]#cam44128-tbl-0002
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quote
Kaplan–Meier survival curves and Cox survival analysis were generated by the “survival” package and “survminer” package in R. The Cox proportional hazard ratio and the 95% confidence interval were included in the survival plot. A log‐rank test was used to evaluate the survival curves between different groups.
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The raw sequencing data files were deposited in the Chinese National Genomics Data Center(https://bigd.big.ac.cn/). Left biospecimens may be shared for academic research under prior approval from the government of China.
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The paper names GSE73731, GSE29069 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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Kaplan–Meier survival curves and Cox survival analysis were generated by the “survival” package and “survminer” package in R. The Cox proportional hazard ratio and the 95% confidence interval were included in the survival plot. A log‐rank test was used to evaluate the survival curves between different groups.
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Previous studies suggested that certain members of MUCINs could serve as independent predictors for the survival of ccRCC patients. None of them, however, is robust enough to predict prognosis accurately.\nOBJECTIVE: To analyze the correlation of MUCINs alterations and their expression levels with the prognosis of ccRCC patients and develop a prognosis-related predictor.\nMETHODS: We applied whole-exome sequencing in samples from 22 Chinese ccRCC patients to identify genetic alterations in MUCIN genes and analyzed their genetic alterations, expression, and correlation with survival using the TCGA, GSE73731, and GSE29069 datasets.\nRESULT: Genetic alternations in MUCINs were identified in 91% and 51% of ccRCC patients in our cohort and the TCGA database, respectively. No correlation with survival was found for the genetic alterations. Using unsupervised clustering analysis of gene expression, we identified two major clusters of MUCIN expression patterns. Cluster 1 was characterized by a global overexpression of MUC1, MUC12, MUC13, MUC16, and OVGP1; and cluster 2 was characterized by a global overexpression of MUC4, MUC5B, MUC6, MUC20, EMCN, and MCAM. Patients with cluster 1 expression pattern had significantly shorter overall survival time and worse clinical features, including higher tumor grades and metastasis. Meanwhile, they had a higher level of mutation counts and more infiltrated immune cells, but lower enrichment in angiogenesis signature genes. A five-MUCINs expression signature was constructed from cluster 1, and notably, it was demonstrated to be associated with shorter overall survival. A similar worse clinical feature, lower angiogenesis but the more immune signature, was identified in samples presented with signature 1. In the validation data set GSE29069, patients with signature 1 were also associated with a trend of poor survival outcomes.\nCONCLUSION: We established a five-MUCINs expression signature as a new prognostic marker for ccRCC. The distinct tumor microenvironment feature between the two signatures may further affect ccRCC patients' clinical management.", "claims": [{"id": "claim-method", "statement": "Kaplan–Meier survival curves and Cox survival analysis were generated by the “survival” package and “survminer” package in R. The Cox proportional hazard ratio and the 95% confidence interval were included in the survival plot. 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