The Oncogenic Role of COL23A1 in Clear Cell Renal Cell Carcinoma

Xu, Fujiang; Chang, Kun; Ma, Jian; Qu, Yuanyuan; Xie, Huyang; Dai, Bo; Gan, Hualei; Zhang, Ye; Shi, Guohai; Zhu, Yao; Zhu, Yiping; Shen, Yijun; Ye, Dingwei

doi:10.1038/s41598-017-10134-2

Cited by 29 publications

(22 citation statements)

References 27 publications

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“…Furthermore, it was indicated that the high-risk group was markedly associated with renal cell carcinoma, bladder cancer and small cell lung cancer. These results were consistent with previous studies that collagen gene expression was correlated with the poor prognosis of those cancers (Koskimaki et al, 2010; Wan et al, 2015; Xu et al, 2017; Zeng et al, 2018).…”

Section: Discussionsupporting

confidence: 93%

The clinical significance of collagen family gene expression in esophageal squamous cell carcinoma

Xiao

Zheng

et al. 2019

PeerJ

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Background Esophageal squamous cell carcinoma (ESCC) is a subtype of esophageal cancer with high incidence and mortality. Due to the poor 5-year survival rates of patients with ESCC, exploring novel diagnostic markers for early ESCC is emergent. Collagen, the abundant constituent of extracellular matrix, plays a critical role in tumor growth and epithelial-mesenchymal transition. However, the clinical significance of collagen genes in ESCC has been rarely studied. In this work, we systematically analyzed the gene expression of whole collagen family in ESCC, aiming to search for ideal biomarkers. Methods Clinical data and gene expression profiles of ESCC patients were collected from The Cancer Genome Atlas and the gene expression omnibus databases. Bioinformatics methods, including differential expression analysis, survival analysis, gene sets enrichment analysis (GSEA) and co-expression network analysis, were performed to investigate the correlation between the expression patterns of 44 collagen family genes and the development of ESCC. Results A total of 22 genes of collagen family were identified as differentially expressed genes in both the two datasets. Among them, COL1A1, COL10A1 and COL11A1 were particularly up-regulated in ESCC tissues compared to normal controls, while COL4A4, COL6A5 and COL14A1 were notably down-regulated. Besides, patients with low COL6A5 expression or high COL18A1 expression showed poor survival. In addition, a 7-gene prediction model was established based on collagen gene expression to predict patient survival, which had better predictive accuracy than the tumor-node-metastasis staging based model. Finally, GSEA results suggested that collagen genes might be tightly associated with PI3K/Akt/mTOR pathway, p53 pathway, apoptosis, cell cycle, etc. Conclusion Several collagen genes could be potential diagnostic and prognostic biomarkers for ESCC. Moreover, a novel 7-gene prediction model is probably useful for predicting survival outcomes of ESCC patients. These findings may facilitate early detection of ESCC and help improves prognosis of the patients.

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Section: Discussionsupporting

confidence: 93%

The clinical significance of collagen family gene expression in esophageal squamous cell carcinoma

Xiao

Zheng

et al. 2019

PeerJ

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“…Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC ( 15 ). A study at our center demonstrated that 88.9% of RCC patients have a clear cell subtype in coastal Chinese areas, consistent with results (87.4%) from the SEER (2004–2012) database ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, it was reported that ccRCC patients have more malignant characteristics and worse prognosis. Further advancements are thus urgently required for ccRCC diagnosis and treatment ( 15 ). In our study, we focused on prognosis prediction for stage III ccRCC patients and constructed a nine-gene signature, using data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases.…”

Section: Introductionmentioning

confidence: 99%

Construction and Validation of a 9-Gene Signature for Predicting Prognosis in Stage III Clear Cell Renal Cell Carcinoma

Jin

et al. 2019

Front. Oncol.

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Purpose: Aim of this study was to develop a multi-gene signature to help better predict prognosis for stage III renal cell carcinoma (RCC) patients.Methods: Fourteen pairs of stage III tumor and normal tissues mRNA expression data from GSE53757 and 16 pairs mRNA expression data from TCGA clear cell RCC database were used to analyze differentially expressed genes between tumor and normal tissues. Common different expressed genes in both datasets were used for further modeling. Lasso Cox regression analysis was performed to select and build prognostic multi-gene signature in TCGA stage III kidney cancer patients (N = 122). Then, the multi-gene signature was validated in stage III renal cancer cases in Fudan University Shanghai Cancer Center (N = 77). C-index and time-dependent ROC were used to test the efficiency of this signature in predicting overall survival.Results: In total, 1,370 common different expressed genes were found between tumor and normal tissues in both datasets. After Lasso Cox modeling, nine mRNAs were finally identified to build a classifier. Using this classifier, we could classify stage III clear cell RCC patients into high-risk group and low-risk group. Prognosis was significantly different between these groups in discovery TCGA cohort, validation FUSCC cohort and entire set (All P < 0.001). Multivariate cox regression in entire set (N = 199) revealed that risk group classified by 9-gene signature, age of diagnosis, pN stage and ISUP grade were independent prognostic factor of overall survival in stage III kidney cancer patients.Conclusion: We developed a robust multi-gene classifier that can effectively classify stage III RCC patients into groups with low and high risk of poor prognosis. This signature may help select high-risk patients who require more aggressive adjuvant target therapy or immune therapy.

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“…22 Silencing type 23 collagen in lung cancer and clear cell renal cell lines showed altered adhesion protein expressions and less ability on cell adhesion and migration. 22,23 However, type 23 collagen is also present in other tissues, and the function and use in other diseases are yet unknown. To our knowledge, this is the first study showing that type 23 collagen level is modulated in IBD.…”

Section: Discussionmentioning

confidence: 99%

Elevated ectodomain of type 23 collagen is a novel biomarker of the intestinal epithelium to monitor disease activity in ulcerative colitis and Crohn's disease

et al. 2021

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Background Impaired intestinal epithelial barrier is highly affected in inflammatory bowel disease. Transmembrane collagens connecting the epithelial cells to the extracellular matrix have an important role in epithelial cell homeostasis. Thus, we sought to determine whether the transmembrane type 23 collagen could serve as a surrogate marker for disease activity in patients with Crohn’s disease and ulcerative colitis. Methods We developed an enzyme-linked immunosorbent assay to detect the ectodomain of type 23 collagen (PRO-C23) in serum, followed by evaluation of its levels in both acute and chronic dextran sulfate sodium colitis models in rats and human inflammatory bowel disease cohorts. Serum from 44 Crohn’s disease and 29 ulcerative colitis patients with active and inactive disease was included. Results In the acute and chronic dextran sulfate sodium-induced rat colitis model, the PRO-C23 serum levels were significantly increased after colitis and returned to normal levels after disease remission. Serum levels of PRO-C23 were elevated in Crohn’s disease ( p < 0.05) and ulcerative colitis ( p < 0.001) patients with active disease compared to healthy donors. PRO-C23 differentiated healthy donors from ulcerative colitis (area under the curve: 0.81, p = 0.0009) and Crohn’s disease (area under the curve: 0.70, p = 0.0124). PRO-C23 differentiated ulcerative colitis patients with active disease from those in remission (Area under the curve: 0.75, p = 0.0219) and Crohn’s disease patients with active disease from those in remission (area under the curve: 0.68, p = 0.05). Conclusion PRO-C23 was elevated in rats with active colitis, and inflammatory bowel disease patients with active disease. Therefore, PRO-C23 may be used as a surrogate marker for monitoring disease activity in ulcerative colitis and Crohn’s disease.

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The Oncogenic Role of COL23A1 in Clear Cell Renal Cell Carcinoma

Cited by 29 publications

References 27 publications

The clinical significance of collagen family gene expression in esophageal squamous cell carcinoma

The clinical significance of collagen family gene expression in esophageal squamous cell carcinoma

Construction and Validation of a 9-Gene Signature for Predicting Prognosis in Stage III Clear Cell Renal Cell Carcinoma

Elevated ectodomain of type 23 collagen is a novel biomarker of the intestinal epithelium to monitor disease activity in ulcerative colitis and Crohn's disease

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