Single-Cell RNA Sequencing Analysis for Oncogenic Mechanisms Underlying Oral Squamous Cell Carcinoma Carcinogenesis with <i>Candida albicans</i> Infection

Single-Cell RNA Sequencing Analysis for Oncogenic Mechanisms Underlying Oral Squamous Cell Carcinoma Carcinogenesis with <i>Candida albicans</i> Infection

Oral squamous cell carcinoma (OSCC) carcinogenesis involves heterogeneous tumor cells, and the tumor microenvironment (TME) is highly complex with many different cell types. Cancer cell–TME interactions are crucial in OSCC progression. <i>Candida albicans</i> (<i>C. albicans</i&...

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Bibliographic Details
Main Authors: Yi-Ping Hsieh, Yu-Hsueh Wu, Siao-Muk Cheng, Fang-Kuei Lin, Daw-Yang Hwang, Shih-Sheng Jiang, Ken-Chung Chen, Meng-Yen Chen, Wei-Fan Chiang, Ko-Jiunn Liu, Nam Cong-Nhat Huynh, Wen-Tsung Huang, Tze-Ta Huang
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:International Journal of Molecular Sciences
Subjects:
tumor heterogeneity
tumor microenvironment
oral squamous cell carcinoma
oral potentially malignant disorder
<i>Candida albicans</i>
single-cell RNA sequencing analysis
Online Access:https://www.mdpi.com/1422-0067/23/9/4833
Description
Summary:Oral squamous cell carcinoma (OSCC) carcinogenesis involves heterogeneous tumor cells, and the tumor microenvironment (TME) is highly complex with many different cell types. Cancer cell–TME interactions are crucial in OSCC progression. <i>Candida albicans</i> (<i>C. albicans</i>)—frequently pre-sent in the oral potentially malignant disorder (OPMD) lesions and OSCC tissues—promotes malignant transformation. The aim of the study is to verify the mechanisms underlying OSCC car-cinogenesis with <i>C. albicans</i> infection and identify the biomarker for the early detection of OSCC and as the treatment target. The single-cell RNA sequencing analysis (scRNA-seq) was performed to explore the cell subtypes in normal oral mucosa, OPMD, and OSCC tissues. The cell composi-tion changes and oncogenic mechanisms underlying OSCC carcinogenesis with <i>C. albicans</i> infec-tion were investigated. Gene Set Variation Analysis (GSVA) was used to survey the mechanisms underlying OSCC carcinogenesis with and without <i>C. albicans</i> infection. The results revealed spe-cific cell clusters contributing to OSCC carcinogenesis with and without <i>C. albicans</i> infection. The major mechanisms involved in OSCC carcinogenesis without <i>C. albicans</i> infection are the IL2/STAT5, TNFα/NFκB, and TGFβ signaling pathways, whereas those involved in OSCC carcinogenesis with <i>C. albicans</i> infection are the KRAS signaling pathway and E2F target down-stream genes. Finally, stratifin (SFN) was validated to be a specific biomarker of OSCC with <i>C. albicans</i> infection. Thus, the detailed mechanism underlying OSCC carcinogenesis with <i>C. albicans</i> infection was determined and identified the treatment biomarker with potential precision medicine applications.
ISSN:1661-6596
1422-0067

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