To Determine the Role of TRIT1 in the Diagnosis, Prognosis and Immunoinvasion of Liver Hepatocellular Carcinoma

Xinyu Niu ¹ Xiaona Pan ² Guifang He ³ Chao Xuan ⁴ Qingwu Tian ⁴ Yuan Yuan ⁴ Jingqiu Chen ¹ Yaqi Song ¹ Yujuan Tang ^5,6* Tingting Zhou ^4*

• ¹ Qingdao University, Qingdao 266000, Shandong, China, Qingdao, Shandong Province, China
• ² Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, China, Qingdao, Shandong Province, China
• ³ Medical Animal Laboratory, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, China, Qingdao, China
• ⁴ Department of Clinical Laboratory, Affiliated Hospital of Qingdao University, Qingdao, China
• ⁵ Department of Surgery, Hubei Provincial Hospital of Traditional Chinese Medicine,Wuhan 430061, Hubei, China, Wuhan, Hebei Province, China
• ⁶ HubeiProvincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Hubei University of Chinese Medicine,Wuhan 430061, Hubei, China, Wuhan, Hebei Province, China

Background: TRIT1 is identified as a potential tumor suppressor gene that may be involved in tumor development. Existing research indicates that TRIT1 is significant in the development of certain cancers. However, its specific role in liver cancer remains elusive.Methods: Expression profiles and clinical data of liver hepatocellular carcinoma (LIHC) patients were retrieved from The Cancer Genome Atlas (TCGA) database. The TRIT1 gene levels between LIHC tissues and normal tissues were compared using the Wilcoxon rank-sum test. Additionally, TRIT1 expression levels were further examined via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Functional enrichment analysis was performed to elucidate the biological pathways associated with TRIT1. Immune cell infiltration patterns were evaluated using single-sample gene set enrichment analysis (ssGSEA). The methylation status of the TRIT1 gene were analyzed using the UALCAN and MethSurv databases. Cox regression analysis and Kaplan-Meier (KM) methods were employed to determine the prognostic value of TRIT1. To create a practical tool for predicting overall survival over time, a nomogram was constructed.Results: The analysis revealed that TRIT1 expression is significantly higher in LIHC tissues compared to normal tissues. Furthermore, elevated TRIT1 levels were found to be associated with specific subtypes of LIHC, including T3 and stage III. Importantly, TRIT1 overexpression was identified as a negative prognostic marker for overall survival in LIHC patients.Additionally, hypermethylation of the TRIT1 gene was associated with poor prognosis. Moreover, this study demonstrated that high TRIT1 levels were correlated with reduced levels of cytotoxic immune cells in the tumor microenvironment, including B cells, cytotoxic cells, and plasmacytoid dendritic cells (pDCs).Conclusions: This study provides the first evidence that the presence of TRIT1 can serve as a reliable marker for diagnosis and prognostication of hepatocellular carcinoma. Moreover, TRIT1 emerges as a critical indicator of the potential for cancer infiltration and invasion of the immune system, holding significant implications for the development of targeted therapies for hepatocellular carcinoma.