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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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
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Online Access:https://www.mdpi.com/1422-0067/23/9/4833
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author 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
author_facet 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
author_sort Yi-Ping Hsieh
collection DOAJ
description 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.
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spelling doaj.art-68c461674ca04d1896e15b22104c1c4e2023-11-23T08:22:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01239483310.3390/ijms23094833Single-Cell RNA Sequencing Analysis for Oncogenic Mechanisms Underlying Oral Squamous Cell Carcinoma Carcinogenesis with <i>Candida albicans</i> InfectionYi-Ping Hsieh0Yu-Hsueh Wu1Siao-Muk Cheng2Fang-Kuei Lin3Daw-Yang Hwang4Shih-Sheng Jiang5Ken-Chung Chen6Meng-Yen Chen7Wei-Fan Chiang8Ko-Jiunn Liu9Nam Cong-Nhat Huynh10Wen-Tsung Huang11Tze-Ta Huang12Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701401, TaiwanInstitute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan 701401, TaiwanNational Institute of Cancer Research, National Health Research Institutes, Tainan 70456, TaiwanInstitute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan 701401, TaiwanNational Institute of Cancer Research, National Health Research Institutes, Tainan 70456, TaiwanNational Institute of Cancer Research, National Health Research Institutes, Zhunan 35053, TaiwanInstitute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan 701401, TaiwanInstitute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan 701401, TaiwanChi Mei Medical Center, Tainan 71004, TaiwanNational Institute of Cancer Research, National Health Research Institutes, Tainan 70456, TaiwanLaboratory of Oral-Maxillofacial Biology, Faculty of Odonto-Stomatology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 749000, VietnamChi Mei Medical Center, Tainan 71004, TaiwanInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701401, TaiwanOral 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.https://www.mdpi.com/1422-0067/23/9/4833tumor heterogeneitytumor microenvironmentoral squamous cell carcinomaoral potentially malignant disorder<i>Candida albicans</i>single-cell RNA sequencing analysis
spellingShingle 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
Single-Cell RNA Sequencing Analysis for Oncogenic Mechanisms Underlying Oral Squamous Cell Carcinoma Carcinogenesis with <i>Candida albicans</i> Infection
International Journal of Molecular Sciences
tumor heterogeneity
tumor microenvironment
oral squamous cell carcinoma
oral potentially malignant disorder
<i>Candida albicans</i>
single-cell RNA sequencing analysis
title Single-Cell RNA Sequencing Analysis for Oncogenic Mechanisms Underlying Oral Squamous Cell Carcinoma Carcinogenesis with <i>Candida albicans</i> Infection
title_full Single-Cell RNA Sequencing Analysis for Oncogenic Mechanisms Underlying Oral Squamous Cell Carcinoma Carcinogenesis with <i>Candida albicans</i> Infection
title_fullStr Single-Cell RNA Sequencing Analysis for Oncogenic Mechanisms Underlying Oral Squamous Cell Carcinoma Carcinogenesis with <i>Candida albicans</i> Infection
title_full_unstemmed Single-Cell RNA Sequencing Analysis for Oncogenic Mechanisms Underlying Oral Squamous Cell Carcinoma Carcinogenesis with <i>Candida albicans</i> Infection
title_short Single-Cell RNA Sequencing Analysis for Oncogenic Mechanisms Underlying Oral Squamous Cell Carcinoma Carcinogenesis with <i>Candida albicans</i> Infection
title_sort single cell rna sequencing analysis for oncogenic mechanisms underlying oral squamous cell carcinoma carcinogenesis with i candida albicans i infection
topic tumor heterogeneity
tumor microenvironment
oral squamous cell carcinoma
oral potentially malignant disorder
<i>Candida albicans</i>
single-cell RNA sequencing analysis
url https://www.mdpi.com/1422-0067/23/9/4833
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