Subtype Of Oral Squamous Cell Carcinoma Research Articles

Comprehensive Bioinformatics Analysis Reveals that N6-Methyladenosine (m6A) Methylation Reader HNRNPC Facilitates Progression of OSCC Through Promoting Epithelial-Mesenchymal Transition(EMT)

Background: M6A is the most widespread RNA internal modification that contributes to the transcription of RNA-mediated genes. Increasing evidence suggest that m6A has vital role in cancer initiation and progression. However, little is known about its roles in oral squamous cell carcinoma(OSCC). Therefore, this study aimed to explore the prognostic relevance of m6A related genes in OSCC through comprehensive bioinformatics analysis. Materials: Transcriptome expression profile were downloaded from The Cancer Genome Atlas (TCGA) following extracting m6A related genes and long non-coding RNA (lncRNA) based on expression level. The differentially expressed genes between OSCC samples and control samples was analyzed using R software. Furthermore, cluster analysis and principal component analysis (PCA) were used to analyze m6A related genes, and a risk model was constructed on basis of m6A related genes. In addition, co-expression network was established according to m6A related genes and differentially expressed lncRNA (DElncRNA) expression profile and crucial m6A genes were selected based on univariate, multivariate cox regression and survival analysis. Then, CCK-8, colony formation assays, transwell assay and scratch wound healing were performed to explore the biological effects of identified m6A-related genes in OSCC. Furthermore, Western blot assay was conducted to detect the EMT-associated genes expression level. Findings: A total of 13 m6A related genes were extracted and 8 genes were differentially expressed in OSCC. Subsequently, 418 DElncRNA were selected. M6A-Based Clustering Shows 2 Subtypes of OSCC with different clinical outcome.Then, a risk model including HNRNPC, METTL14, YTHDF2, ALKBH5 genes was established on basis of m6A expression profile, which can indicate the survival time and differentiation grade and may be an independent prognostic biomarkers. Furthermore, a co-expression network including 7 m6A related genes and 21 DElncRNA was constructed based on DElncRNA and m6A related genes and HNRNPC was identified as an independent prognostic biomarker in OSCC. Functional studies revealed that HNRNPC knockdown inhibited cell proliferation, migration and invasion of OSCC cells in vitro. Conversely, HNRNPC overexpression showed the opposite biological effects. Moreover, we identified that HNRNPC regulated epithelial-mesenchymal transition in OSCC. Interpretation: This study revealed that m6A may play a significant role in OSCC initiation and progression through integrated bioinformatics analysis. And co-expression network may be helpful for revealing potential correlation of lncRNA and m6A in OSCC. In addition, a risk model was established to predict the prognosis of OSCC.At last, HNRNPC was proved to promote OSCC carcinogenisis and be an independent prognostic biomarker of OSCC, suggesting that it may be a new therapeutic target of OSCC. Funding Statement:This study was supported by the National Natural Science Foundation of China (81472536); the Science and Technology Planning Project of Guangdong Province (No. 2017A020215181 and No. 2014A020212440); Project of Educational Commission of Guangdong Province of China (2018KTSCX026); the Scientific Research Planning Project of Southern Medical University (CX2018N016, PY2018N031) and the Presidential Foundation of the Nanfang Hospital (2014027, 2019Z030). Declaration of Interests: All authors declare no conflicts of interest. Ethics Approval Statement: The study protocol was approved by the Ethics Committees of Nanfang Hospital of Guangdong Province (NO: NFEC-2018-027).

The Role of Sonic Hedgehog Signaling in the Tumor Microenvironment of Oral Squamous Cell Carcinoma.

Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of SHH expression appear to correlate with cancer progression. However, the role of SHH in the tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC) is still unclear. No studies have compared the expression of SHH in different subtypes of OSCC and focused on the relationship between the tumor parenchyma and stroma. In this study, we analyzed SHH and expression of its receptor, Patched-1 (PTCH), in the TME of different subtypes of OSCC. Fifteen endophytic-type cases (ED type) and 15 exophytic-type cases (EX type) of OSCC were used. H&E staining, immunohistochemistry (IHC), double IHC, and double-fluorescent IHC were performed on these samples. ED-type parenchyma more strongly expressed both SHH and PTCH than EX-type parenchyma. In OSCC stroma, CD31-positive cancer blood vessels, CD68- and CD11b-positive macrophages, and α-smooth muscle actin-positive cancer-associated fibroblasts partially expressed PTCH. On the other hand, in EX-type stroma, almost no double-positive cells were observed. These results suggest that autocrine effects of SHH induce cancer invasion, and paracrine effects of SHH govern parenchyma-stromal interactions of OSCC. The role of the SHH pathway is to promote growth and invasion.

A novel comparison of Epstein-Barr virus with broad histological spectrum of oral squamous cell carcinoma

Objectives:To evaluate the immunohistochemical expression of Epstein-Barr virus (EBV) in broad spectrum histological subtypes of oral squamous cell carcinoma (OSCC) and to determine the relationship of EBV with clinicopathological parameters of OSCC.Methods:This cross-sectional study included 150 clinically diagnosed OSCC cases from the outpatient of Ziauddin University Hospital from March, 2017 to October, 2018. These were confirmed on histological examination and categorized into conventional squamous cell carcinoma (SCC) and rare variants. Conventional SCC was subcategorized into keratinizing (KSCC), non-keratinizing (NKSCC), and hybrid SCC (HSCC). EBV status was compared among various histological tumor entities and clinicopathological characteristics of OSCC using immunohistochemistry. Chi-square test was used to determine the association of each histological subtype with EBV status with P-value <0.05 considered as statistically significant.Results:Conventional tumor was the most frequent squamous cell carcinoma (n=126; 84%). A significant statistical link of EBV infection was observed with rare histological tumors exhibiting acantholysis (P=0.01), as well as tumors involving buccal mucosa (P=0.03), and habitual smokers (P=0.001).Conclusions:In this study, acantholytic tumor, a rare histological subtype of OSCC, tended to be EBV related. Moreover, OSCC cases bearing EBV infection were more likely smokers favoring buccal mucosa as primary anatomical site for oral cancer.

A novel genomic signature reclassifies an oral cancer subtype.

Verrucous carcinoma of the oral cavity (OVC) is considered a subtype of classical oral squamous cell carcinoma (OSCC). Diagnosis is problematic, and additional biomarkers are needed to better stratify patients. To investigate their molecular signature, we performed low-coverage copy number (CN) sequencing on 57 OVC and exome and RNA sequencing on a subset of these and compared the data to the same OSCC parameters. CN results showed that OVC lacked any of the classical OSCC patterns such as gain of 3q and loss of 3p and demonstrated considerably fewer genomic rearrangements compared to the OSCC cohort. OVC and OSCC samples could be clearly differentiated. Exome sequencing showed that OVC samples lacked mutations in genes commonly associated with OSCC (TP53, NOTCH1, NOTCH2, CDKN2A and FAT1). RNA sequencing identified genes that were differentially expressed between the groups. In silico functional analysis showed that the mutated and differentially expressed genes in OVC samples were involved in cell adhesion and keratinocyte proliferation, while those in the OSCC cohort were enriched for cell death and apoptosis pathways. This is the largest and most detailed genomic and transcriptomic analysis yet performed on this tumour type, which, as an example of non-metastatic cancer, may shed light on the nature of metastases. These three independent investigations consistently show substantial differences between the cohorts. Taken together, they lead to the conclusion that OVC is not a subtype of OSCC, but should be classified as a distinct entity.