A Potential Diagnostic and Prognostic Biomarker TMEM176B and Its Relationship With Immune Infiltration in Skin Cutaneous Melanoma

Linlan Jiang; Yanyin Yang; Fangming Liu; Mingyue Ma; Jie Gao; Lu Sun; Yuwen Chen; Zan Shen; Duojiao Wu

doi:10.3389/fcell.2022.859958

A Potential Diagnostic and Prognostic Biomarker TMEM176B and Its Relationship With Immune Infiltration in Skin Cutaneous Melanoma

Front Cell Dev Biol. 2022 Mar 23:10:859958. doi: 10.3389/fcell.2022.859958. eCollection 2022.

Authors

Linlan Jiang¹, Yanyin Yang², Fangming Liu³, Mingyue Ma², Jie Gao³, Lu Sun³, Yuwen Chen⁴, Zan Shen¹, Duojiao Wu⁴

Affiliations

¹ Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
² Department of Endocrinology and Metabolism, Zhongshan Hospital, Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Fudan University, Shanghai, China.
³ Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai, China.
⁴ Jinshan Hospital Center for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai, China.

Abstract

Background: Melanoma is a highly malignant and aggressive tumor. The search for new and effective biomarkers facilitates early diagnosis and treatment, ultimately improving the prognosis of melanoma patients. Although the transmembrane protein TMEM176B has been linked to a number of cancers, its role in cancer immunity remains unknown. Methods: Expression levels of TMEM176B in normal tissues and several cancers, including Skin Cutaneous Melanoma (SKCM), were collected from TCGA and GTEx. We used Receiver operating characteristic and Kaplan-Meier survival curves and performed regression analysis to elucidate the link between TMEM176B and clinicopathological features of SKCM in order to determine the prognostic significance of TMEM176B in SKCM. We then used the GEPIA and STRING websites to search for proteins and associated top genes that may interact with TMEM176B and enriched them for analysis. The link between TMEM176B and immune cells infiltration was then investigated using TIMER, CIBERSORT algorithm and GSVA package of R (v3.6.3). Finally, animal tests were conducted to confirm the expression of Tmem176b and its influence on T-cell immune infiltration. Results: TMEM176B expression was considerably elevated in SKCM compared to normal tissues. Particularly, TMEM176B expression was also linked to pathological stage, tumor ulceration and radiation therapy. Patients with elevated TMEM176B expression had a better prognosis, according to the survival analysis. The majority of tumor infiltrating lymphocytes (TILs) especially T cells in SKCM was positively linked with TMEM176B expression. Our animal experiments also verified that the T-cell infiltration was significantly inhibited in local melanoma tissue of Tmem176b knockout mice. At the same time deleting Tmem176b accelerated tumor progress and impaired T cells effector function. Conclusion: Upregulated expression of TMEM176B in SKCM is associated with a better prognosis and it has the potential to serve as a diagnostic and prognostic marker for the disease. It may serve as a target for SKCM immunotherapy by regulating CD8⁺ T cells although it requires more evidence.

Keywords: CD8+ T cell; SKCM; TMEM176B; cancer; tumor immunology.