Characterization of the Clinical Significance and Immunological Landscapes of a Novel TMEMs Signature in Hepatocellular Carcinoma and the Contribution of TMEM201 to Hepatocarcinogenesis

Author:

Chen Desheng1,Lou Yichao1,Lu Jing1,Fan Xuhui2,Zhu Qi1,Sun Hongcheng1

Affiliation:

1. Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China

2. Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China

Abstract

Aberrant transmembrane protein (TMEM) expression is implicated in tumor progression, but its functional role in hepatocellular carcinoma (HCC) is unclear. Thus, we aim to characterize the functional contributions of TMEM in HCC. In this study, four novel TMEM-family genes (TMEMs), TMEM106C, TMEM201, TMEM164, and TMEM45A, were screened to create a TMEMs signature. These candidate genes are distinguished between patients with varying survival statuses. High-risk HCC patients had a significantly worse prognosis and more advanced clinicopathological characteristics in both the training and validation groups. The GO and KEGG analyses unveiled that the TMEMs signature might play a crucial role in cell-cycle-relevant and immune-related pathways. We found that the high-risk patients had lower stromal scores and a more immunosuppressive tumor microenvironment with massive infiltration of macrophages and Treg cells, whereas the low-risk group had higher stromal scores and gamma delta T-cell infiltration. Moreover, the expression level of suppressive immune checkpoints increased as the TMEM-signature scores increased. Furthermore, the in vitro experiments validated TMEM201, one feature of the TMEMs signature, and facilitated HCC proliferation, survival, and migration. The TMEMs signature provided a more precise prognostic evaluation of HCC and reflected the immunological status of HCC. Of the TMEMs signature studied, TMEM201 was found to significantly promote HCC progression.

Funder

Natural Science Foundation of Shanghai

the Clinical Research Innovation Plan of Shanghai General Hospital

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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