AUTHOR=Han Songling , Zhu Wei , Yang Weili , Guan Qijie , Chen Chao , He Qiang , Zhong Zhuoheng , Zhao Ruoke , Xiong Hangming , Han Haote , Li Yaohan , Sun Zijian , Hu Xingjiang , Tian Jingkui 

TITLE=A Prognostic Signature Constructed by CTHRC1 and LRFN4 in Stomach Adenocarcinoma

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.646818

DOI=10.3389/fgene.2021.646818

ISSN=1664-8021

ABSTRACT=<sec><title>Background</title><p>Stomach adenocarcinoma (STAD) is the most common histological type of stomach cancer, which causes a considerable number of deaths worldwide. This study aimed to identify its potential biomarkers with the notion of revealing the underlying molecular mechanisms.</p></sec><sec><title>Methods</title><p>Gene expression profile microarray data were downloaded from the Gene Expression Omnibus (GEO) database. The “limma” R package was used to screen the differentially expressed genes (DEGs) between STAD and matched normal tissues. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for function enrichment analyses of DEGs. The STAD dataset from The Cancer Genome Atlas (TCGA) database was used to identify a prognostic gene signature, which was verified in another STAD dataset from the GEO database. CIBERSORT algorithm was used to characterize the 22 human immune cell compositions. The expression of <italic>LRFN4</italic> and <italic>CTHRC1</italic> in tissues was determined by quantitative real-time PCR from the patients recruited to the present study.</p></sec><sec><title>Results</title><p>Three public datasets including 90 STAD patients and 43 healthy controls were analyzed, from which 44 genes were differentially expressed in all three datasets. These genes were implicated in biological processes including cell adhesion, wound healing, and extracellular matrix organization. Five out of 44 genes showed significant survival differences. Among them, <italic>CTHRC1</italic> and <italic>LRFN4</italic> were selected for construction of prognostic signature by univariate Cox regression and stepwise multivariate Cox regression in the TCGA-STAD dataset. The fidelity of the signature was evaluated in another independent dataset and showed a good classification effect. The infiltration levels of multiple immune cells between high-risk and low-risk groups had significant differences, as well as two immune checkpoints. <italic>TIM-3</italic> and <italic>PD-L2</italic> were highly correlated with the risk score. Multiple signaling pathways differed between the two groups of patients. At the same time, the expression level of <italic>LRFN4</italic> and <italic>CTHRC1</italic> in tissues analyzed by quantitative real-time PCR were consistent with the <italic>in silico</italic> findings.</p></sec><sec><title>Conclusion</title><p>The present study constructed the prognostic signature by expression of <italic>CTHRC1</italic> and <italic>LRFN4</italic> for the first time <italic>via</italic> comprehensive bioinformatics analysis, which provided the potential therapeutic targets of STAD for clinical treatment.</p></sec>