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

Abstract

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. Candida albicans (C. albicans)—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 C. albicans 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 C. albicans infec-tion were investigated. Gene Set Variation Analysis (GSVA) was used to survey the mechanisms underlying OSCC carcinogenesis with and without C. albicans infection. The results revealed spe-cific cell clusters contributing to OSCC carcinogenesis with and without C. albicans infection. The major mechanisms involved in OSCC carcinogenesis without C. albicans infection are the IL2/STAT5, TNFα/NFκB, and TGFβ signaling pathways, whereas those involved in OSCC carcinogenesis with C. albicans 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 C. albicans infection. Thus, the detailed mechanism underlying OSCC carcinogenesis with C. albicans infection was determined and identified the treatment biomarker with potential precision medicine applications.

Comprehensive Integrated Single-Cell Whole Transcriptome Analysis Revealed the p-EMT Tumor Cells—CAFs Communication in Oral Squamous Cell Carcinoma

“…In the total cell sample of OSCC tumors, we identified 15 main cell types that were confirmed previously in both human and mouse samples [ 1 , 5 ]. The main populations were composed of immune cells and non-immune cells, including cancer-associated cells that were similar to HNSCC data [ 12 , 18 ].…”

“…Single-cell RNA-seq datasets for oral squamous cell carcinoma (GSE103322 and GSE164690) were downloaded from Gene Expression Omnibus database ( , (accessed on 4 May 2022), , (accessed on 4 May 2022)) [ 12 , 18 ]. We combined our single-cell RNA-seq data as previously reported [ 1 ]. Only samples with oral cavity site, primary tumor, and metastasis status characteristics were included in the downstream analysis using the Seurat R package (v4) [ 50 ].…”

“…Head and neck cancers, including head and neck squamous cell carcinoma (HNSCC) and oral squamous cell carcinoma (OSCC), are a heterogeneous collection of malignancies of the upper aerodigestive tract, salivary glands, and thyroid [ 1 , 2 ]. It is estimated that more than 830,000 individuals have suffered from this disease, which caused over 430,000 deaths worldwide each year [ 3 ].…”

Effect of method and concentration of titanium dioxide addition on anti-biofilm ability in extraoral maxillofacial prosthetic fungus

“…microorganisms than common disinfectants. 17 When it is used as a coating, TiO₂ is able to maintain the color and mechanical properties of a material. 2 Candida albicans has a thick cell wall because it consists of glucan and chitin which makes it stronger than bacteria.…”

Single‐cell RNA sequencing reveals the heterogeneity of epithelial cell and fibroblast cells from non‐ to metastatic lymph node OTSCC

“…To increase the sample size, we obtained single‐cell RNA‐seq datasets for oral squamous cell carcinoma (GSE172577 and GSE163872) from Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE172577, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE163872). The single‐cell RNA‐seq data was integrated in accordance with the methodology described in a previously reported study 14 . The downstream analysis used Seurat R package (v4) exclusively incorporated samples that possessed the features of tongue, primary tumor, and lymph nodes metastatic status 15 .…”