Application Potential of CTHRC1 as a Diagnostic and Prognostic Indicator for Colon Adenocarcinoma.

Chen Pang,Hongwei Wang,Houjie Liang,Chengcheng Shen

doi:10.3389/fmolb.2022.849771

Abstract

Colon adenocarcinoma (COAD), ranking third in incidence and second in mortality, is one of the most common cancer types in the world. The initial stages of COAD usually show no obvious clinical symptoms; moreover, effective screening or diagnostic indicators with high sensitivity and specificity are lacking, which often leads to missed treatment opportunities. Collagen triple helix repeat containing 1 (CTHRC1) is a glycosylated protein secreted during tissue repair, which reduces collagen matrix deposition and promotes cell migration. Under physiological conditions, the expression of CTHRC1 is conducive to wound healing; however, the pathological overexpression of CTHRC1 promotes tumour growth and proliferation. In this study, we evaluated the application potential of CTHRC1 as an early diagnosis and prognostic survival monitoring biomarker for COAD in addition to unravelling its molecular mechanism in the development of COAD and exploring new therapeutic targets. Therefore, various tumour databases were used to investigate the expression of CTHRC1 in COAD at the mRNA and protein levels. CTHRC1 expression was found to be significantly increased in COAD, regardless of clinical cancer stage, age, sex or race. Moreover, CTHRC1 expression was significantly correlated with poor prognosis and positively correlated with CD8+ T cell, CD4+ T cell, neutrophil, macrophage and dendritic cell infiltration. The relevant function pathways and neighbouring proteins to CTHRC1 in COAD were identified as ROR2, VAPA, LY6E and several collagen family proteins. Therefore, this study suggests that CTHRC1 is a potential diagnostic and prognostic biomarker for patients with COAD.

Highlights

A recent study by the American Cancer Society reported that colorectal cancer has the third highest (10.0%) incidence rate after female breast cancer (11.7%) and lung cancer (11.4%) (Sung et al, 2021)
RNA-seq data extracted from TCGA database showed a consistent trend of abnormally high Collagen triple helix repeat containing 1 (CTHRC1) expression in more than 16 types of tumour tissues compared with the corresponding normal tissues, such as Colon adenocarcinoma (COAD), breast invasive carcinoma and stomach adenocarcinoma (Figure 1A)
Oncomine analysis of the pathological samples showed that the transcriptional levels of CTHRC1 mRNA were significantly up-regulated in various cancer types including colorectal cancer (Figure 1B)

Summary

Introduction

A recent study by the American Cancer Society reported that colorectal cancer has the third highest (10.0%) incidence rate after female breast cancer (11.7%) and lung cancer (11.4%) (Sung et al, 2021). Based on the current prediction models, the global incidence of colorectal cancer has been estimated to reach approximately 2.2 million new cases/year by 2030, accounting for 20% of all patients with cancer (Araghi et al, 2018). The official statistics on the prognosis of patients with colorectal cancer published by the American Cancer Society report that. Early diagnosis or detection of colorectal cancer at stage I, stage IIA or IIB increases the 5 years survival rate to approximately 90%; delayed diagnosis decreases the survival rate of patients with pathological stage IV tumour to approximately 14% (Pilonis et al, 2020). The current screening of colorectal cancer has been strengthened, resulting in a slight decrease in late diagnosis case numbers, up to 90% of cases are diagnosed after symptoms appear (Vanessa and Karen, 2016)

Objectives

Methods

Results

Conclusion