Identification of Biomarkers Related to Regulatory T Cell Infiltration in Oral Squamous Cell Carcinoma Based on Integrated Bioinformatics Analysis

Abstract

Background: Oral squamous cell carcinoma (OSCC) is one of the most prevalent malignancies worldwide. More recently, the administration of immune checkpoint inhibitors has opened up more possibilities for cancer treatment. Methods: We utilized a weighted gene co-expression network and the single sample gene set enrichment analysis (ssGSEA) algorithm in the TCGA database and identified a module highly correlated with regulatory T cell (Treg) abundance in OSCC. Subsequently, we verified the results by tissue microarrays and utilized immunohistochemical staining (IHC) to test the relationship between the expression level and clinicopathological staging. CCK-8, transwell, and wound healing assays were utilized to detect the functions of OSCC cells. Results: LCK, IL10RA, and TNFRSF1B were selected as biomarkers related to regulatory T cell infiltration. IHC staining showed significantly increased expression of LCK, IL10RA or TNFRSF1B in OSCC patients, and the expression levels were associated with tumor stage, lymph node metastasis, pathological stage, clinical status and the overall survival. In vitro experiments showed that LCK, IL10RA or TNFRSF1B knockdown efficiently impaired the proliferative, migrative, and invasive capacity in OSCC cell lines. Conclusion:We performed a series of bioinformatics analyses in OSCC and identified three oncogenic indicators: LCK, IL10RA, TNFRSF1B. These findings uncovered the potential prognostic values of hub genes, thus laying foundations for in-depth research in OSCC.

Molecular profiling of core immune-escape genes highlights LCK as an immune-related prognostic biomarker in melanoma

“…Overexpression of LCK contributes to a large number of other diseases such as cancer, systemic lupus erythematosus and organ transplant rejection ( 43 ). It has been reported that knockdown of LCK significantly inhibits cell proliferation and cell invasion in Oral squamous cell carcinoma (OSCC) ( 44 ). Another report stated that inhibition or downregulation of LCK led to apoptosis in Chronic Lymphocytic Leukemia (CLL) cell lines ( 45 ).…”

Low‐dose TNF‐α promotes angiogenesis of oral squamous cell carcinoma cells via TNFR2/Akt/mTOR axis

“…Given the above key roles of TNFR2 in tumor cell survival, angiogenesis, and immune escape, targeting TNFR2 is becoming an important strategy for tumor therapy (Al‐hatamleh et al., 2020; Li et al., 2022; Segués et al., 2021). However, in the case of OSCCs, the expression and function of TNFR2 have been rarely studied (Wang et al., 2022), and whether TNF‐α promotes paracrine signaling in tumor cells for angiogenesis via TNFR2 remains unclear. In addition, sustained endothelial activation of Akt has been shown to induce the formation of abnormal blood vessels, and the Akt/mTOR pathway has been implicated in the regulation of angiogenesis (Karar & Maity, 2011).…”