scholarly journals The Intersection between Oral Microbiota, Host Gene Methylation and Patient Outcomes in Head and Neck Squamous Cell Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3425
Author(s):  
Zigui Chen ◽  
Po Yee Wong ◽  
Cherrie W. K. Ng ◽  
Linlin Lan ◽  
Sherwood Fung ◽  
...  

The role of oral microbiota in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Here we sought to evaluate the association of the bacterial microbiome with host gene methylation and patient outcomes, and to explore its potential as a biomarker for early detection or intervention. Here we performed 16S rRNA gene amplicon sequencing in sixty-eight HNSCC patients across both tissue and oral rinse samples to identify oral bacteria with differential abundance between HNSCC and controls. A subset of thirty-one pairs of HNSCC tumor tissues and the adjacent normal tissues were characterized for host gene methylation profile using bisulfite capture sequencing. We observed significant enrichments of Fusobacterium and Peptostreptococcus in HNSCC tumor tissues when compared to the adjacent normal tissues, and in HNSCC oral rinses when compared to healthy subjects, while ten other bacterial genera were largely depleted. These HNSCC-related bacteria were discriminative for HNSCC and controls with area under the receiver operating curves (AUCs) of 0.84 and 0.86 in tissue and oral rinse samples, respectively. Moreover, Fusobacterium nucleatum abundance in HNSCC cases was strongly associated with non-smokers, lower tumor stage, lower rate of recurrence, and improved disease-specific survival. An integrative analysis identified that enrichment of F. nucleatum was associated with host gene promoter methylation, including hypermethylation of tumor suppressor genes LXN and SMARCA2, for which gene expressions were downregulated in the HNSCC cohort from The Cancer Genome Atlas. In conclusion, we identified a taxonomically defined microbial consortium associated with HNSCC that may have clinical potential regarding biomarkers for early detection or intervention. Host–microbe interactions between F. nucleatum enrichment and clinical outcomes or host gene methylation imply a potential role of F. nucleatum as a pro-inflammatory driver in initiating HNSCC without traditional risk factors, which warrants further investigation for the underlying mechanisms.

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Tengjiao Zhu ◽  
Yingtong Chen ◽  
Shuyuan Min ◽  
Fang Li ◽  
Yun Tian

The mammalian orosomucoid-like gene family (ORMDL), containing ORMDL1, ORMDL2, and ORMDL3, is the important regulator of sphingolipid metabolism, which is relevant to cell growth, proliferation, migration, and invasion. Since the role of ORMDL1 in cancers remained unclear, the main purpose of our study was to explore the expression patterns and prognostic values of ORMDL1 in different tumors, especially in cholangiocarcinoma (CHOL), lymphoid neoplasm diffuse large B cell lymphoma (DLBCL), acute myeloid leukemia (LAML), and thymoma (THYM). Bioinformatics tools including GEPIA, CCLE, LinkedOmics, cBioPortal, and TIMER databases were used. As a result, the expression levels of ORMDL1 in tumor tissues and normal tissues varied in different cancers, especially significantly upregulated in CHOL, DLBCL, LAML, and THYM. Moreover, ORMDL1 mRNA was also highly expressed in cell lines of DLBCL and LAML. Further studies showed that ORMDL1 overexpression was associated with poor prognosis in DLBCL, but not significant in CHOL, LAML, and THYM. Consistently, there were genetic alterations of ORMDL1 in DLBCL, and patients with genetic alterations indicated worse survival. Coexpressed genes and related biological events with ORMDL1 in DLBCL were found via LinkedOmics, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The relationship between ORMDL1 and cancer immune cells was investigated, and ORMDL1 expression was positively correlated with infiltrating levels of B cells. In conclusion, ORMDL1 is suggested to be a tumorigenic factor and considered as the potential therapeutic target and prognostic biomarker in DLBCL.


ABSTRACT Introduction Oral cancer is a potentially fatal disease, which constitutes an important portion of tumors of the head and neck region. Among head and neck cancers, oral squamous cell carcinomas (OSCCs) constitute 90% of total cancers. Regardless of the fact that the oral cavity is easily accessible to the accumulation of carcinogens, most oral cancers are typically detected at an advanced stage leading to lower survival rate among subjects. Abnormal cellular products elucidated from malignant cells can be detected and measured in various body fluids including saliva, which constitute tumor markers. Saliva, an aqueous biological fluid, is in direct contact with the oral cancer lesion. Hence, the saliva in any stage of oral cancer constitutes abnormal deoxyribonucleic acid (DNA), acid (RNA), and protein molecules. Saliva, being a noninvasive diagnostic aid, can be an alternative to serum for early detection, status of chemotherapy regime, and also patient prognosis. This article aims at providing a brief overview of various salivary biomarkers and their implications in oral cancer. How to cite this article Gupta P. Role of Salivary Biomarkers for Early Detection of Oral Squamous Cell Carcinoma. Int J Adv Integ Med Sci 2017;2(3):155-160.


Author(s):  
Yongzhi XU ◽  
Fang FANG ◽  
Jinghui WANG ◽  
Chunli ZHAO ◽  
Jingyang ZHAO ◽  
...  

Background: Expression of miR‑92b in oral squamous cell carcinoma (OSCC) rat tissue and its effect on the OSCC CAL‑27 cells were investigated. Methods: The study was performed in Qingdao Stomatological Hospital, Qingdao, China on December 2018. Thirty Wistar rats were used to construct models of oral squamous cell carcinoma. CAL‑27 cells trascfected by Lipofectamine 2000 were divided into miR‑92b inhibitor, miR‑NC and blank groups. RT‑qPCR was used for the detection of the expression level of miR‑92b, and MTT and flow cytometry were carried out for the detection of the effect of miR‑92b on the proliferation and apoptosis of CAL‑27 cells, respectively. Results: The expression level of miR‑92b was significantly higher in tumor tissues than that in normal tissues (P<0.001). The miR‑92b inhibitor group had significantly lower proliferation ability but higher apoptosis rate of CAL‑27 cells than the miR‑NC and blank groups. After miR‑92b was downregulated by trans-fecting cells, the expression level of miR‑92b was significantly lower in the miR‑92b inhibitor group than that in the miR‑NC and blank groups. Conclusion: miR‑92b inhibitor can inhibit the proliferation of CAL‑27 cells and promote apoptosis, which provides certain references for clinical treatment. It is expected to be a potential target for treating OSCC.


2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Heqing Lai ◽  
Guochao Xu ◽  
Haifeng Meng ◽  
Haiying Zhu

Abstract Objective: To study the association between SP1 rs1353058818 and STAT3 rs1053004 gene polymorphisms and risk of human tongue squamous cell carcinoma (TSCC). Methods: Sanger sequencing was used to determine the genotypes of SP1 rs1353058818 and STAT3 rs1053004 loci in 240 TSCC patients and 240 controls. Levels of hsa-miR-149-5p and hsa-miR-21-5p and expression levels of SP1 and STAT3 proteins in tumor tissues and adjacent normal tissues of TSCC patients were ascertained. Results: Carrying the SP1 rs1353058818 locus deletion allele was a high risk factor for TSCC (OR = 2.997, 95% CI: 1.389–6.466, P = 0.003). The STAT3 rs1053004 locus A allele was a protective factor for TSCC (OR = 0.604, 95% CI: 0.460-0.793, P < 0.001). There was a negative correlation between SP1 mRNA and hsa-miR-149-5p in tumor and adjacent normal tissues (r = −0.81, −0.77). The expression of SP1 protein in tumor tissues of the SP1 rs1353058818 locus DD genotype was significantly higher than in tissues of the ID type, and in tissues of type II it was the lowest. STAT3 mRNA was positively correlated with hsa-miR-21-5p in tumor and adjacent normal tissues (r = 0.75, 0.78). The expression level of STAT3 protein in tumor tissues of patients with STAT3 rs1053004 locus GG genotype was significantly higher than in patients with type GA, and it was the lowest in patients with type AA. Conclusion: Polymorphisms in the SP1 rs1353058818 and STAT3 rs1053004 loci are associated with the risk of human TSCC.


2016 ◽  
Vol 21 (4) ◽  
pp. 201-206
Author(s):  
O. I Kit ◽  
E. N Kolesnikov ◽  
E. M Frantsiyants ◽  
Larisa S. Kozlova ◽  
Yu. A Pogorelova ◽  
...  

Aim. The purpose of the study was to perform the comparative analysis of the components ofplasminogen activation system - uPA and tPA, and their inhibitor PAI-1 in tissues of esophageal adenocarcinoma (EA) and squamous cell carcinoma (SCC). Tissues of removed primary both EA (n=9, st II, G2, T2-3N0-1M0-1) and SCC (n=27, st II, G2, T2-3N0-1M0-1) were studied by ELISA. Results. EA and SCC tumor tissues showed a sharp increase in both uPA forms and in PAI-1, in EA tissue there was noted a decrease in all tPA and in SCC tissue there was seen a decline in tPA-act, compared to the resection line (RL). Perifocal zone of EA showed diminished uPA-Ag, all tPA, increased uPA-act and all PAI-1, compared to the RL. uPA and PAI-1 play an important role in progression of both SCC and EA. The role of tPA requires the further studying, but in SCC perifocal zone its impact may be rather harmful than protective. tPA-Ag/tPA-act balance was increased in SCC tissue only, while in other samples it was decreased (p


2018 ◽  
Vol 28 (4) ◽  
pp. 95-98 ◽  
Author(s):  
Daniel Rodger ◽  
Jacinda Hammerschlag

Acute compartment syndrome as a result of an extravasation injury is rare. The perioperative environment presents a unique risk that may contribute to more serious patient outcomes. Using a case study approach we report that the placement of a pulse oximeter on the cannulated limb can provide the first sign of vascular compromise.


Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1842
Author(s):  
Yawei Sun ◽  
Shuai Wang ◽  
Xingwei Zhang ◽  
Zhuhao Wu ◽  
Zihui Li ◽  
...  

Background: Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a key enzyme that catalyzes the hydroxylation of lysine, plays a crucial role in the progression of several solid tumors. However, its spatial expression profile and prognostic significance in oral squamous cell carcinoma (OSCC) have not been revealed. Materials: Mass spectrometry was used to explore amino acid perturbations between OSCC tumor tissues and paired normal tissues of 28 patients. Then, PLOD2 mRNA and protein levels were assessed using several public databases and 18 pairs of OSCC patients’ tissues. Additionally, PLOD2 spatial expression profiles were investigated in 100 OSCC patients by immunohistochemistry and its diagnostic and prognostic values were also evaluated. Lastly, gene set enrichment analysis (GSEA) was used to investigate the potential functions of PLOD2 in OSCC. Results: Lysine was significantly elevated in OSCC tissues and could effectively distinguish tumor from normal tissues (AUC = 0.859, p = 0.0035). PLOD2 mRNA and protein levels were highly increased in tumor tissues of head and neck squamous cell carcinoma (HNSCC) (p < 0.001) and OSCC compared with those in nontumor tissues (p < 0.001). Histopathologically, PLOD2 was ubiquitously expressed in tumor cells (TCs) and fibroblast-like cells (FLCs) of OSCC patients but absent in tumor-infiltrating lymphocytes (TILs). Patients with highly expressed PLOD2 in TCs (PLOD2TCs) and FLCs (PLOD2FLCs) showed poor differentiation, a worse pattern of invasion (WPOI) and more lymph node metastasis (LNM), contributing to higher postoperative metastasis risk and poor survival time. However, PLOD2FLCs rather than PLOD2TCs was an independent risk factor for survival outcomes in OSCC patients. Molecularly, GSEA demonstrated highly expressed PLOD2 was mainly enriched in epithelial–mesenchymal transformation (EMT), TGF-beta signaling and hypoxia pathway, which are associated with poor clinical outcomes of OSCC patients. Conclusions: PLOD2 was a poor prognostic biomarker for OSCC patients and may affect the metastasis of OSCC through EMT pathway. These findings might shed novel sights for future research in PLOD2 targeted OSCC therapy.


2021 ◽  
Vol 9 (8) ◽  
pp. 1549
Author(s):  
Tereza Vyhnalova ◽  
Zdenek Danek ◽  
Daniela Gachova ◽  
Petra Borilova Linhartova

Dysbiosis in the oral environment may play a role in the etiopathogenesis of oral squamous cell carcinoma (OSCC). This review aims to summarize the current knowledge about the association of oral microbiota with OSCC and to describe possible etiopathogenetic mechanisms involved in processes of OSCC development and progression. Association studies included in this review were designed as case–control/case studies, analyzing the bacteriome, mycobiome, and virome from saliva, oral rinses, oral mucosal swabs, or oral mucosal tissue samples (deep and superficial) and comparing the results in healthy individuals to those with OSCC and/or with premalignant lesions. Changes in relative abundances of specific bacteria (e.g., Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus sp.) and fungi (especially Candida sp.) were associated with OSCC. Viruses can also play a role; while the results of studies investigating the role of human papillomavirus in OSCC development are controversial, Epstein–Barr virus was positively correlated with OSCC. The oral microbiota has been linked to tumorigenesis through a variety of mechanisms, including the stimulation of cell proliferation, tumor invasiveness, angiogenesis, inhibition of cell apoptosis, induction of chronic inflammation, or production of oncometabolites. We also advocate for the necessity of performing a complex analysis of the microbiome in further studies and of standardizing the sampling procedures by establishing guidelines to support future meta-analyses.


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