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SECTM1 is upregulated in immuno-hot tumors and predicts immunotherapeutic efficacy in multiple cancers.

ABSTRACT: Immune checkpoint inhibitors (ICIs) have transformed the management of advanced cancers. However, many patients could not benefit from ICIs therapy, and thus several biomarkers for therapeutic prediction have been uncovered. In this research, more than ten public and in-house cohorts were used to explore the predictive value and immunological correlations of secreted and transmembrane 1 (SECTM1) in cancers. SECTM1 expression was enhanced in tumors from patients with well immunotherapeutic responses in multiple cancers. In addition, SECTM1 was immuno-correlated in pan-cancer and enhanced in immuno-hot tumors. In vitro assays revealed that SECTM1 was upregulated by the IFN-γ/STAT1 signaling. Moreover, analysis of in-house immunotherapy cohorts suggested both tumor-expressed and circulating SECTM1 are promising biomarkers to predict therapeutic responses. Overall, this study reveals that SECTM1 is a biomarker of benefit to ICIs in cancer patients. Further studies including large-scale patients are needed to establish its utilization as a biomarker of benefit to ICIs.

SUBMITTER: Mei J

PROVIDER: S-EPMC9932126 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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SECTM1 is upregulated in immuno-hot tumors and predicts immunotherapeutic efficacy in multiple cancers.

Mei Jie J Fu Ziyi Z Cai Yun Y Song Chenghu C Zhou Jiaofeng J Zhu Yichao Y Mao Wenjun W Xu Junying J Yin Yongmei Y

iScience 20230123 2

Immune checkpoint inhibitors (ICIs) have transformed the management of advanced cancers. However, many patients could not benefit from ICIs therapy, and thus several biomarkers for therapeutic prediction have been uncovered. In this research, more than ten public and in-house cohorts were used to explore the predictive value and immunological correlations of secreted and transmembrane 1 (SECTM1) in cancers. SECTM1 expression was enhanced in tumors from patients with well immunotherapeutic respon ...[more]

PMID: 36818292

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Project description:BackgroundShort stature homeobox 2 (SHOX2) is significant gene in the development and progression of multiple types of tumors. Nonetheless, the biological role of SHOX2 within pan-cancer datasets has not been investigated. Thus, comprehensive bioinformatics analyses of pan-cancer datasets were conducted to explore how SHOX2 regulates tumorigenesis.MethodsA variety of tumor datasets and online analytical tools, including SangerBox, TIMER2, LinkedOmic, GEPIA2 and cBioPortal, were applied to explore SHOX2 expression in various tumors. To ascertain the connections between SHOX2 expression and genetic alterations, SHOX2-related genes and tumor immunity, the pan-cancer datasets were examined. In vitro assays were applied to verify the biological functions of SHOX2 in glioma cells via CCK-8, wound healing, Transwell and colony formation assays.ResultsAnalyses found that SHOX2 was overexpressed in multiple cancer types. SHOX2 expression level was significantly correlated with isocitrate dehydrogenase (IDH), 1p/19q, O6-methylguanine DNA methyltransferase (MGMT) status and new types of glioma patients. High mRNA expression levels of SHOX2 were associated with a poor prognosis in multiple tumor patients. KEGG enrichment analysis showed that SHOX2-related genes were associated with cell cycle and DNA damage repair. Genetic alterations of SHOX2 were identified in multiple types of cancers, including duplications and deep mutations. Immune analysis showed that SHOX2 was closely correlated with the tumor mutation burden (TMB), microsatellite instability (MSI), neoantigen and neoantigens and immune checkpoint (ICP) in a variety of tumors and could influence the immunotherapy sensitivity of cancers. CCK-8, wound healing, Transwell and colony formation experiments showed that SHOX2 knockdown inhibited glioma cell proliferation, migration, invasion and colony formation abilities.ConclusionSHOX2 was overexpressed in multiple cancer types in TCGA cohort. SHOX2 knockdown inhibited glioma cell proliferation, migration and colony formation ability. Our study showed that SHOX2 may be an immunotherapeutic and promising prognostic biomarker in certain types of tumors.

Dataset Information

SECTM1 is upregulated in immuno-hot tumors and predicts immunotherapeutic efficacy in multiple cancers.

Publications

SECTM1 is upregulated in immuno-hot tumors and predicts immunotherapeutic efficacy in multiple cancers.

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