COL12A1, a novel potential prognostic factor and therapeutic target in gastric cancer

Abstract

Dysregulation of collagen type XII α1 chain (COL12A1) has been found in several cancer types and could be involved in tumor progression. However, its clinical significance in gastric cancer (GC) remains under exploration. Online databases (Gene Expression Omnibus and UALCAN), reverse transcription-quantitative PCR and immunohistochemistry were utilized in the present study to evaluate the expression of COL12A1 in GC tissues and cell lines. It was found that COL12A1 expression was notably upregulated in GC. Clinicopathological analysis showed that elevated COL12A1 expression was positively correlated with tumor invasiveness, metastasis and advanced clinical stage. The prognostic analysis suggested that high COL12A1 expression contributed to poor overall survival. Multivariate Cox analysis indicated that COL12A1 overexpression was a powerful independent prognostic indicator in patients with GC (hazard ratio, 1.896; 95% CI, 1.267–2.837; P=0.002). The results highlighted the importance of COL12A1 in GC and suggested its potential role as a candidate for clinical outcome prediction and targeted therapy in patients with GC.

The Extracellular Matrix: An Accomplice in Gastric Cancer Development and Progression

“…Several collagen genes were found to be overexpressed in gastric cancer and, among these, COL1A1 and COL4A1 were closely associated with overall survival of gastric cancer patients and could be regarded as risk factors for poor prognosis [9]. The expression of COL12A1 was also found upregulated in gastric cancer and positively correlated with tumor invasiveness, metastasis, and advanced clinical stage [8]. In tumor tissues of gastric cancer patients, levels of collagen type-I and -IV, fibronectin, and laminin were markedly higher than those detected in the normal tissues [60].…”

“…Abnormal ECM and integrin profiles are frequently reported in cancer corroborating the functional relevance and the specificity of both ECM In gastric cancer, the role of the ECM has been undeniably demonstrated in all steps of the disease, from initiation to metastases. For instance, increased expression of tenascin has been detected in pre-malignant and malignant gastric epithelia [7], whereas collagens have been shown to be deregulated in more advanced stages [8][9][10]. Notably, a subset of collagen genes have been suggested as powerful independent prognostic markers and are able to distinguish pre-malignant from malignant lesions [8][9][10].…”

“…Several studies have provided evidence that the ECM contributes to cancer pathogenesis by (i) stimulating integrin-dependent signaling that promotes invasion and proliferation; (ii) promoting an advantageous microenvironmental niche for metastatic cells; (iii) serving as a reservoir of growth factor and cytokines; (iv) interfering with the communication between cancer and immune cells; and (v) forming a physical barrier to anti-cancer agents ( Figure 1) [4,6].In gastric cancer, the role of the ECM has been undeniably demonstrated in all steps of the disease, from initiation to metastases. For instance, increased expression of tenascin has been detected in pre-malignant and malignant gastric epithelia [7], whereas collagens have been shown to be deregulated in more advanced stages [8][9][10]. Notably, a subset of collagen genes have been suggested as powerful independent prognostic markers and are able to distinguish pre-malignant from malignant lesions [8][9][10].…”

“…For instance, increased expression of tenascin has been detected in pre-malignant and malignant gastric epithelia [7], whereas collagens have been shown to be deregulated in more advanced stages [8][9][10]. Notably, a subset of collagen genes have been suggested as powerful independent prognostic markers and are able to distinguish pre-malignant from malignant lesions [8][9][10]. It is thus foreseen that ECM components and interactors hold great clinical potential as prognostic biomarkers and pharmacological targets in gastric cancer.This review comprises a comprehensive analysis of the main studies concerning ECM remodeling and integrin alterations during gastric cancer development.…”

Identification of Core Prognosis-Related Candidate Genes in Chinese Gastric Cancer Population Based on Integrated Bioinformatics

“…COL12A1 , a gene encoding collagen type XII alpha 1 chain, is a typical collagen-organizer molecule involved in collagen cross-linking in the cancer microenvironment [ 40 ]. The expression of COL12A1 in GC tissues increased significantly, and the elevated COL12A1 protein level was positively correlated with aggressive clinical features [ 41 ]. VCAN is a chondroitin sulfate proteoglycan.…”