Identifying GNG4 might play an important role in colorectal cancer TMB

Article type: Research Article

Authors: Zhao, Hongcan^{a; 1} | Sheng, Danli^{b; 1} | Qian, Ze^c | Ye, Sunyi^d | Chen, Jianzhong^{e; f; h; *} | Tang, Zhe^{g; h; *}

Affiliations: [a] Department of Laboratory Medicine, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China | [b] Pathology Department, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China | [c] Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China | [d] Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China | [e] Institute of Immunology School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China | [f] Key Laboratory of Immunity and Inflammatory Diseases of Zhejiang Province, Hangzhou, Zhejiang, China | [g] Department of Surgery, Forth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, Zhejiang, China | [h] Department of Surgery, Second Affiliated hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

Correspondence: [*] Corresponding authors: Jianzhong Chen, Institute of Immunology, School of Medicine, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China. Tel./Fax: +86 87342564; E-mail: chenjianzhong@zju.edu.cn. Zhe Tang, Department of Surgery, Second Affiliated hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. Tel./Fax: +86 87783563; E-mail: 8xi@zju.edu.cn.

Note: [1] The first three authors are co-first authors.

Abstract: BACKGROUND: Colorectal carcinoma (CRC) is one of the most leading cause of cancer death all over the world. The tumor immune microenvironment is illustrated to be necessary for the progress of CRC. And the accumulating evidence indicated that tumor mutation burden (TMB) is effective in differentiating responding population of immune checkpoint inhibitor (ICI) therapies in various cancers. In this study, we aimed to evaluated the potential relationship between TMB and the recurrence risk of CRC. METHODS: The transcriptomic and clinical data of CRC patients were collected from The Cancer Genome Atlas (TCGA) database (n= 382). Then the genomic analysis of tumor mutation burden and tumor purity were conducted by a computational method based on transcriptomic data. RESULTS: Firstly, we accessed the distribution of TMB and preferences at the gene and mutation level using somatic mutation data from TCGA data about CRC. We identified that high TMB predicted better prognosis of CRC patients. Secondly, the differentially expressed genes (DEGs) between the low TMB and high TMB group was clarified. Then the protein-protein interaction (PPI) analysis was performed, and the results confirmed ten hub genes among the DEGs. Utilizing the GEPIA web-tool, we discovered that GNG4 was up-regulated in tumor tissues, and GNG4 was related to the overall survival (OS) and tumor free survival (TFS) of CRC patients. Therefore, we considered GNG4 was essential for the tumor immune microenvironment of CRC. Furthermore, we also accessed the protein level of GNG4 in CRC and liver metastases from CRC. CONCLUSIONS: In this study, GNG4 was demonstrated to be the key element of the CRC TMB, which will be essential for the ICI therapy of CRC. Besides, GNG4 was up-regulated in CRC and liver metastases from CRC tissues. Thus, we thought that GNG4 might play an important role in colorectal cancer TMB and induce its metastasis in liver.

Keywords: CRC, tumor mutation burden, prognosis, GNG4, TCGA

DOI: 10.3233/CBM-203009

Journal: Cancer Biomarkers, vol. 32, no. 4, pp. 435-450, 2021