Prognostic value of COL6A3 in pancreatic adenocarcinoma

Svoronos, Christos; Tsoulfas, Georgios; Souvatzi, Maria; Chatzitheoklitos, Efthimios

doi:10.14701/ahbps.2020.24.1.52

Cited by 17 publications

(13 citation statements)

References 23 publications

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“…3), encoding the α-3 chain of type VI collagen, which has been found to participate in the tumor malignant processes in gastric, pancreatic, and ovarian cancer [14]. So we hypothesized that circCOL6A3_030 also played an important role in the malignant progression of gastric cancer.…”

Section: Discussionmentioning

confidence: 97%

circCOL6A3_030 is involved in the metastasis of gastric cancer by encoding polypeptide

Pan

Geng

Wang

et al. 2020

Preprint

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Background Gastric cancer (GC) is a serious digestive tract disease that threatens human life worldwide, and the prognosis of gastric cancer accompanied by distant lymph node or the distant metastasis organs is worse. The purpose of this study was to investigate the role of circular RNA COL6A3_030 (circBase ID: hsa_circ_0006401; circRNADb ID: hsa_circ_28198; circBank ID: hsa_circCOL6A3_030) in GC metastasis. Methods qRT-PCR analysis using back-splicing primers and Sanger sequencing of PCR products were performed to identify circCOL6A3_030 in GC tissues and cell lines; RNA-FISH assay was performed to validate the subcellular localization of circCOL6A3_030. Transwell and wound-healing assays were carried out to evaluate the migration ability of GC cells. Western blot was conducted to detect the polypeptide encoded by circCOL6A3_030 in cells. Results circCOL6A3_030 was down-regulated in GC tissues and cell lines, while circCOL6A3_030 was up-regulated in GC with distant lymph node metastasis. The migration of circCOL6A3_030 silenced GC cells was significantly inhibited in both SGC-7901 and BGC-823 cell lines. Importantly, in vivo assay, silencing circCOL6A3_030 could reduce liver metastases from gastric cancer cells. Meanwhile, further studies suggested that circCOL6A3_030 encoded a small peptide that had a function as a tumor-promoting metastasis factor and immunohistochemistry confirmed the presence of this polypeptide. Conclusions To sum up, our study showed that circCOL6A3_030 promoted GC cell migration by encoding a small peptide called circCOL6A3_030_198aa. Therefore, our results highlight the potential role of circCOL6A3_030 for clinical diagnosis and treatment of GC with distant lymph node metastasis.

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Section: Discussionmentioning

confidence: 97%

circCOL6A3_030 is involved in the metastasis of gastric cancer by encoding polypeptide

Pan

Geng

Wang

et al. 2020

Preprint

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“…Svoronos et al. ( 54 ) showed that in the PDAC stroma, COL6A3 is the major overexpressed gene, and overexpressed COL6A3 leads to a poor prognosis in PDAC. Arafat et al.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of a Prognostic miRNA Signature and Potential Key Genes in Pancreatic Cancer

Chen

Gao

et al. 2021

Front. Oncol.

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BackgroundIn this study, miRNAs and their critical target genes related to the prognosis of pancreatic cancer were screened based on bioinformatics analysis to provide targets for the prognosis and treatment of pancreatic cancer.MethodsR software was used to screen differentially expressed miRNAs (DEMs) and genes (DEGs) downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, respectively. A miRNA Cox proportional hazards regression model was constructed based on the miRNAs, and a miRNA prognostic model was generated. The target genes of the prognostic miRNAs were predicted using TargetScan and miRDB and then intersected with the DEGs to obtain common genes. The functions of the common genes were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. A protein-protein interaction (PPI) network of the common genes was constructed with the STRING database and visualized with Cytoscape software. Key genes were also screened with the MCODE and cytoHubba plug-ins of Cytoscape. Finally, a prognostic model formed by the key gene was also established to help evaluate the reliability of this screening process.ResultsA prognostic model containing four downregulated miRNAs (hsa-mir-424, hsa-mir-3613, hsa-mir-4772 and hsa-mir-126) related to the prognosis of pancreatic cancer was constructed. A total of 118 common genes were enriched in two KEGG pathways and 33 GO functional annotations, including extracellular matrix (ECM)-receptor interaction and cell adhesion. Nine key genes related to pancreatic cancer were also obtained: MMP14, ITGA2, THBS2, COL1A1, COL3A1, COL11A1, COL6A3, COL12A1 and COL5A2. The prognostic model formed by nine key genes also possessed good prognostic ability.ConclusionsThe prognostic model consisting of four miRNAs can reliably predict the prognosis of patients with pancreatic cancer. In addition, the screened nine key genes, which can also form a reliable prognostic model, are significantly related to the occurrence and development of pancreatic cancer. Among them, one novel miRNA (hsa-mir-4772) and two novel genes (COL12A1 and COL5A2) associated with pancreatic cancer have great potential to be used as prognostic factors and therapeutic targets for this tumor.

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“…Strong evidence had demonstrated COL6A1-3's role in promoting the progression of tumors [37]. COL6A2 was dysregulated and associated with poor prognosis by involving in TGFβ1 pathway in serous ovarian cancer [38,39]. COL6A3 may take part in the tumorigenesis and progression of cholangiocarcinoma through E2F1/LMCD1-AS1/miR-345-5p/COL6A3 axis and might act as a prognostic factor for pancreatic cancer [40].…”

Section: Discussionmentioning

confidence: 99%

Key Genes Associated With Prognosis and Metastasis of Clear Cell Renal Cell Carcinoma

Zhong

Jiang

Wang

et al. 2021

Preprint

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Background: Clear cell renal cell carcinoma (ccRCC) is a tumor with frequent hematogenous metastasis and is usually resistant with radiotherapy and chemotherapy. The mechanism of ccRCC metastasis still needs to be illustrated.Material and methods: The differentially expressed genes (DEGs) of three gene expression profiles (GSE85258, GSE105288 and GSE22541) downloaded from Gene Expression Omnibus (GEO) database were analyzed by GEO2R analysis, and co-expressed DEGs among them were sorted out by the online Venn drawing tool. The co-expressed DEGs were then investigated using Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and hub genes would be screened out based on protein-protein interaction network (PPI) established by STRING. After survival analysis performed on UALCAN website, possible key genes would be selected and then verified in ccRCC cell lines and ccRCC tissues (n=40). Statistical analysis of the above results was conducted using GraphPad Prism (Version 8.1.1).Results: 104 co-expressed DEGs were sorted from the three profiles. KEGG pathways revealed that these genes were enriched in the extracellular matrix (ECM)-receptor interaction, focal adhesion and PI3K-Akt signaling pathway. Survival analysis showed that among 17 hub genes, patients with higher expression of Procollagen C-Endopeptidase Enhancer (PCOLCE), Prolyl 4-Hydroxylase Subunit Beta (P4HB), Collagen Type VI Alpha 2 (COL6A2), and Collagen Type VI Alpha 3 (COL6A3) had a worse survival than those with lower expression. In vitro, the mRNA expression level of PCOLCE, P4HB and COL6A2 were 3 times, and COL6A3 16 times higher in metastatic ccRCC cell line Caki-1 than in corresponding primary cell line Caki-2. Immunohistochemistry results also showed higher expression of these 4 genes in metastatic ccRCC with statistical significance.Conclusion: PCOLCE, P4HB, COL6A2 and COL6A3 are upregulated in metastatic ccRCC and might be related to poor prognosis and distant metastases.

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Prognostic value of COL6A3 in pancreatic adenocarcinoma

Cited by 17 publications

References 23 publications

circCOL6A3_030 is involved in the metastasis of gastric cancer by encoding polypeptide

circCOL6A3_030 is involved in the metastasis of gastric cancer by encoding polypeptide

Bioinformatics Analysis of a Prognostic miRNA Signature and Potential Key Genes in Pancreatic Cancer

Key Genes Associated With Prognosis and Metastasis of Clear Cell Renal Cell Carcinoma

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