scholarly journals Identification of Hypoxia-Related Molecular Classification and Associated Gene Signature in Oral Squamous Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Chen Li ◽  
Xin Chen ◽  
Xiaolin Ren ◽  
Jia-lin Chen ◽  
Hao Chen ◽  
...  

The high heterogeneity of oral squamous cell carcinoma (OSCC) is the main obstacle for individualized treatment. Recognizing the characteristics of different subtypes and investigating the promising strategies for each subclass are of great significance in precise treatment. In this study, we systematically evaluated hypoxia-mediated patterns together with immune characteristics of 309 OSCC patients in the TCGA training set and 97 patients in the GSE41613 testing set. We further identified two different hypoxia subtypes with distinct immune microenvironment traits and provided treatment programs for the two subclasses. In order to assess hypoxia level individually, we finally constructed a hypoxia-related risk score, which could predict the clinical outcome and immunotherapy response of OSCC patients. In summary, the recognition of different hypoxia patterns and the establishment of hypoxia-related risk score might enhance our understanding of the tumor microenvironment of OSCC and provide more personalized treatment strategies in the future.

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guichuan Huang ◽  
Jing Zhang ◽  
Ling Gong ◽  
Yi Huang ◽  
Daishun Liu

Abstract Background Lung cancer is one of the most lethal and most prevalent malignant tumors worldwide, and lung squamous cell carcinoma (LUSC) is one of the major histological subtypes. Although numerous biomarkers have been found to be associated with prognosis in LUSC, the prediction effect of a single gene biomarker is insufficient, especially for glycolysis-related genes. Therefore, we aimed to develop a novel glycolysis-related gene signature to predict survival in patients with LUSC. Methods The mRNA expression files and LUSC clinical information were obtained from The Cancer Genome Atlas (TCGA) dataset. Results Based on Gene Set Enrichment Analysis (GSEA), we found 5 glycolysis-related gene sets that were significantly enriched in LUSC tissues. Univariate and multivariate Cox proportional regression models were performed to choose prognostic-related gene signatures. Based on a Cox proportional regression model, a risk score for a three-gene signature (HKDC1, ALDH7A1, and MDH1) was established to divide patients into high-risk and low-risk subgroups. Multivariate Cox regression analysis indicated that the risk score for this three-gene signature can be used as an independent prognostic indicator in LUSC. Additionally, based on the cBioPortal database, the rate of genomic alterations in the HKDC1, ALDH7A1, and MDH1 genes were 1.9, 1.1, and 5% in LUSC patients, respectively. Conclusion A glycolysis-based three-gene signature could serve as a novel biomarker in predicting the prognosis of patients with LUSC and it also provides additional gene targets that can be used to cure LUSC patients.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Chi T. Viet ◽  
Gary Yu ◽  
Kesava Asam ◽  
Carissa M. Thomas ◽  
Angela J. Yoon ◽  
...  

Abstract Background Oral squamous cell carcinoma (OSCC) is a capricious cancer with poor survival rates, even for early-stage patients. There is a pressing need to develop more precise risk assessment methods to appropriately tailor clinical treatment. Genome-wide association studies have not produced a viable biomarker. However, these studies are limited by using heterogeneous cohorts, not focusing on methylation although OSCC is a heavily epigenetically-regulated cancer, and not combining molecular data with clinicopathologic data for risk prediction. In this study we focused on early-stage (I/II) OSCC and created a risk score called the REASON score, which combines clinicopathologic characteristics with a 12-gene methylation signature, to predict the risk of 5-year mortality. Methods We combined data from an internal cohort (n = 515) and The Cancer Genome Atlas (TCGA) cohort (n = 58). We collected clinicopathologic data from both cohorts to derive the non-molecular portion of the REASON score. We then analyzed the TCGA cohort DNA methylation data to derive the molecular portion of the risk score. Results 5-year disease specific survival was 63% for the internal cohort and 86% for the TCGA cohort. The clinicopathologic features with the highest predictive ability among the two the cohorts were age, race, sex, tobacco use, alcohol use, histologic grade, stage, perineural invasion (PNI), lymphovascular invasion (LVI), and margin status. This panel of 10 non-molecular features predicted 5-year mortality risk with a concordance (c)-index = 0.67. Our molecular panel consisted of a 12-gene methylation signature (i.e., HORMAD2, MYLK, GPR133, SOX8, TRPA1, ABCA2, HGFAC, MCPH1, WDR86, CACNA1H, RNF216, CCNJL), which had the most significant differential methylation between patients who survived vs. died by 5 years. All 12 genes have already been linked to survival in other cancers. Of the genes, only SOX8 was previously associated with OSCC; our study was the first to link the remaining 11 genes to OSCC survival. The combined molecular and non-molecular panel formed the REASON score, which predicted risk of death with a c-index = 0.915. Conclusions The REASON score is a promising biomarker to predict risk of mortality in early-stage OSCC patients. Validation of the REASON score in a larger independent cohort is warranted.


2006 ◽  
Vol 12 (20) ◽  
pp. 5960-5971 ◽  
Author(s):  
Amy F. Ziober ◽  
Kirtesh R. Patel ◽  
Faizan Alawi ◽  
Phyllis Gimotty ◽  
Randall S. Weber ◽  
...  

2012 ◽  
Vol 13 (2) ◽  
pp. 194-200
Author(s):  
Sonam C Kapse ◽  
Ajit V Koshy ◽  
Nirmala N Rao ◽  
Sushant S Kamat ◽  
Kamal Kiswani ◽  
...  

ABSTRACT Aim To evaluate the expression of laminin in various grades of oral squamous cell carcinoma (OSCC) in order to determine whether this protein can be used as a marker for early detection and elucidation of oral cancer. Materials and methods Immunohistochemical staining for laminin was done on 60 selected archival blocks of histopathologically diagnosed cases of primary OSCC and the laminin expression was compared between the different histopathological grades of primary OSCC. The statistical analysis was performed by using Chi-square (÷ square) test and Gaussiantest with a probability of p < 0.05 was considered as significant. Results It was observed that laminin expression decreased with tumor progression which may be correlated to the tumor aggressiveness. Conclusion There was a gradual decrease of laminin staining with decreasing cellular differentiation, with differentiated lesions showing a more conspicuous staining of basement membrane glycoprotein than less differentiated lesions. Clinical significance An understanding of how the extracellular matrix influences tumor development and invasion is fundamental in the development of new prognostic indicators and treatment strategies for oral squamous cell carcinoma. How to cite this article Koshy AV, Rao NN, Kamat SS, Kiswani K, Kapse SC, Shaikh NA. Expression of Extracellular Matrix— Laminin in Oral Squamous Cell Carcinoma: An Immunohistochemical Study. J Contemp Dent Pract 2012;13(2):194-200.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jiahang Song ◽  
Yanhu Liu ◽  
Xiang Guan ◽  
Xun Zhang ◽  
Wenda Yu ◽  
...  

Esophageal squamous cell carcinoma (ESCC) accounts for the main esophageal cancer (ESCA) type, which is also associated with the greatest malignant grade and low survival rates worldwide. Ferroptosis is recently discovered as a kind of programmed cell death, which is indicated in various reports to be involved in the regulation of tumor biological behaviors. This work focused on the comprehensive evaluation of the association between ferroptosis-related gene (FRG) expression profiles and prognosis in ESCC patients based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). ALOX12, ALOX12B, ANGPTL7, DRD4, MAPK9, SLC38A1, and ZNF419 were selected to develop a novel ferroptosis-related gene signature for GEO and TCGA cohorts. The prognostic risk model exactly classified patients who had diverse survival outcomes. In addition, this study identified the ferroptosis-related signature as a factor to independently predict the risk of ESCC. Thereafter, we also constructed the prognosis nomogram by incorporating clinical factors and risk score, and the calibration plots illustrated good prognostic performance. Moreover, the association of the risk score with immune checkpoints was observed. Collectively, the proposed ferroptosis-related gene signature in our study is effective and has a potential clinical application to predict the prognosis of ESCC.


2016 ◽  
Vol 113 (41) ◽  
pp. 11549-11554 ◽  
Author(s):  
Jau-Song Yu ◽  
Yi-Ting Chen ◽  
Wei-Fan Chiang ◽  
Yung-Chin Hsiao ◽  
Lichieh Julie Chu ◽  
...  

Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan’s Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.


2017 ◽  
Vol 34 (2) ◽  
pp. 92-99 ◽  
Author(s):  
Lisa A. Mestrinho ◽  
Hugo Pissarra ◽  
Sandra Carvalho ◽  
Maria C. Peleteiro ◽  
Jerzy Gawor ◽  
...  

Grade and labeling indices for immunohistochemical tumor proliferation markers Ki-67 and proliferating cell nuclear antigen (PCNA) were evaluated in 36 cases of canine oral squamous cell carcinoma (OSCC) based upon intraoral location. Grade was significantly associated with location ( P = .035). Grade II tumors were most frequently diagnosed. Grade I tumors were identified in the gingiva and the buccal mucosa, and grade III tumors were seen in the gingiva and the tonsillar region. Animals with tumors arising from the tonsils and of the tongue tended to be older ( P = .007), and those in the former group were more likely to have metastatic disease at the time of diagnosis ( P = .001). Mean expression of PCNA and Ki-67 proliferation index (PI) for all tumors were 62.54% and 50.70%, respectively, and there was a statistical significant association between the 2 variables ( R = .70; P < .001). Proliferation index was not associated with any of the intraoral locations evaluated, but higher PCNA PI was significantly associated with grade ( P = .031). Ki-67 PI was significantly associated with lymph node metastasis at the time of diagnosis, especially for OSCC of gingival location ( P = .028). The results obtained in this study are preliminary but clinically relevant, since they provide information that can explain differences in biologic behavior among intraoral locations and contribute to more accurate tumor staging to support the choice for different treatment strategies available for OSCC.


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