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

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.859958

DOI=10.3389/fcell.2022.859958

ISSN=2296-634X

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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 <italic>Tmem176b</italic> and its influence on T-cell immune infiltration.</p><p><bold>Results:</bold><italic>TMEM176B</italic> expression was considerably elevated in SKCM compared to normal tissues. Particularly, <italic>TMEM176B</italic> expression was also linked to pathological stage, tumor ulceration and radiation therapy. Patients with elevated <italic>TMEM176B</italic> 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 <italic>TMEM176B</italic> expression. Our animal experiments also verified that the T-cell infiltration was significantly inhibited in local melanoma tissue of <italic>Tmem176b</italic> knockout mice. At the same time deleting <italic>Tmem176b</italic> accelerated tumor progress and impaired T cells effector function.</p><p><bold>Conclusion:</bold> 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<sup>+</sup> T cells although it requires more evidence.</p>