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

Chao Wang; Zhihong Chen; Xueming Yang; Wei Zhang; Junbo Zhou; Hongchuang Zhang; Xu Ding; Jinhai Ye; Heming Wu; Yunong Wu; Yang Zheng; Xiaomeng Song

doi:10.2147/IJGM.S349379

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

Int J Gen Med. 2022 Mar 2:15:2361-2376. doi: 10.2147/IJGM.S349379. eCollection 2022.

Authors

Chao Wang^#^{1

2}, Zhihong Chen^#^{1

2}, Xueming Yang^#^{1

3}, Wei Zhang¹, Junbo Zhou⁴, Hongchuang Zhang⁵, Xu Ding^{1

2}, Jinhai Ye^{1

2}, Heming Wu^{1

2}, Yunong Wu^{1

2}, Yang Zheng^{1

6}, Xiaomeng Song^{1

2}

Affiliations

¹ Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
² Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
³ Department of Stomatology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
⁴ Department of Stomatology, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Nanjing, Jiangsu, People's Republic of China.
⁵ Department of Stomatology, Xuzhou No. 1 People's Hospital, Xuzhou, Jiangsu, People's Republic of China.
⁶ Department of Oral Maxillofacial & Head and Neck Oncology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Disease, National Center of Stomatology, Shanghai, People's Republic of China.

^# Contributed equally.

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.

Keywords: IL10RA; LCK; TNF receptor superfamily member 1B; TNFRSF1B; interleukin 10 receptor subunit alpha; lymphocyte cell-specific protein-tyrosine kinase; oral squamous cell carcinoma; regulatory T cell.

Grants and funding

Our research was funded by the National Natural Science Foundation of China (81402236, 81772887), Jiangsu Provincial Medical Innovation Team (CXTDA2017036), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD, 2018-87), Jiangsu Provincial Medical Youth Talent (QNRC2016854) and Natural Science Foundation of Jiangsu Province of China (BK20171488).