Abstract
The extracellular matrix (ECM) is reported to be involved in tumorigenesis and progression. Collagen IIX is a major ECM protein. Abnormal COL12A1 expression is associated with carcinogenesis of colorectal cancer (CRC), but its clinical value and function have not yet been analyzed. Expression, methylation, and survival were analyzed by using Oncomine, UNCLA, and GEPIA, while COL12A1 alterations and related functional networks were identified using cBioPortal. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathways（KEGG）of COL12A1 in CRC were explored using LinkOmics. Gene set enrichment analysis (GSEA) examined target networks of kinases, miRNAs, and transcription factors. We found that COL12A1 was overexpressed in CRC and the COL12A1 gene was often amplified in CRC. Survival analysis revealed that patients with higher COL12A1 expression had a poor prognosis. Expression of COL12A1 was linked to functional networks via regulating pathways involving focal adhesion, PI3K‐Akt signaling pathway, and ECM‐receptor interaction. Functional network analysis suggested that COL12A1 regulated integrin binding, collage binding, and extracellular matrix structural constituent via pathways involving some several cancer‐related kinases, miRNAs, and transcription factor. Furthermore, other FACITs genes (COL1A2, COL3A1, COL5A1, COL5A2, and COL6A3) for ECM in correlation with COL12A1 were identified to be related with the prognosis in CRC. These results suggested that the distinct fibril‐associated collagens with interrupted triple helices (FACITs) genes may serve as prognostic and therapeutic biomarkers of CRC in the future.
Highlights
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death worldwide.[1]
Combined with the above results, we identified that other fibril-associated collagens with interrupted triple helices (FACITs) proteins (COL1A2, COL3A1, COL5A1, COL5A2, and COL6A3) for extracellular matrix (ECM) in correlation with COL12A1 were co-expressed in CRC
Further subgroup analysis of multiple clinicopathological parameters of CRC samples consistently showed high transcription of COL12A1. These results suggested COL12A1 as an oncogene for CRC and it might be used to stratify populations with high risk according to the expression of COL12A1
Summary
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death worldwide.[1]. While the pathogenesis of CRC is very complex process involving in signal transduction and cell proliferation regulation, which reflects the interaction and function of multiple genes at multiple steps.[3]. Underlying pathogenesis of CRC by analyzing genetic alterations correlated with tumorigenesis and progression is essential for identifying new drug targets for CRC. Studies have reported that collage XII triggers signaling pathways to regulate cell migration and invasion,[8] inflammation,[9] and tumor growth.[10]. Other studies found that abnormal increasing expression of COL12A1 was detected in ovary cancer (OC) and COL12A1 overexpression induced drug resistance in OC cell lines.[11,12]. Our current study aimed to investigate the transcriptional profile, methylation, survival data, somatic mutation, and function of COL12A1 gene in correlation with CRC occurrence by using integrated bioinformatics methods. We studied genomic alteration of COL12A1 and its functional networks in CRC using multidimensional analysis. Our work could potentially identify novel biomarkers in CRC, optimizing current therapeutic strategies for patients
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