scholarly journals Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan

2016 ◽  
Vol 113 (41) ◽  
pp. 11549-11554 ◽  
Author(s):  
Jau-Song Yu ◽  
Yi-Ting Chen ◽  
Wei-Fan Chiang ◽  
Yung-Chin Hsiao ◽  
Lichieh Julie Chu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Risk Score ◽  
Squamous Cell ◽  
Low Risk ◽  
Healthy Controls ◽  
Protein Biomarkers

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.

scholarly journals Novel Autophagy-Related Gene Signature Investigation for Patients With Oral Squamous Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Lihong Huang ◽  
Xinghao Yu ◽  
Zhou Jiang ◽  
Ping Zeng
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Risk Score ◽  
Squamous Cell ◽  
Cox Regression ◽  
Risk Group ◽  
Low Risk ◽  
Related Gene

The correlation between autophagy defects and oral squamous cell carcinoma (OSCC) has been previously studied, but only based on a limited number of autophagy-related genes in cell lines or animal models. The aim of the present study was to analyze differentially expressed autophagy-related genes through The Cancer Genome Atlas (TCGA) database to explore enriched pathways and potential biological function. Based on TCGA database, a signature composed of four autophagy-related genes (CDKN2A, NKX2-3, NRG3, and FADD) was established by using multivariate Cox regression models and two Gene Expression Omnibus datasets were applied for external validation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to study the function of autophagy-related genes and their pathways. The most significant GO and KEGG pathways were enriched in several key pathways that were related to the progression of autophagy and OSCC. Furthermore, a prognostic risk score was constructed based on the four genes; patients were then divided into two groups (i.e., high risk and low risk) in terms of the median of risk score. Prognosis of the two groups and results showed that patients at the low-risk group had a much better prognosis than those at the high-risk group, regardless of whether they were in the training datasets or validation datasets. Multivariate Cox regression results indicated that the risk score of the autophagy-related gene signatures could greatly predict the prognosis of patients after controlling for several clinical covariates. The findings of the present study revealed that autophagy-related gene signatures play an important role in OSCC and are potential prognostic biomarkers and therapeutic targets.

A Four-gene Autophagy-related Prognostic Signature and Its Association With Immune Landscape in Lung Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Lumeng Luo ◽  
Minghe Lv ◽  
Xuan Li ◽  
Tiankui Qiao ◽  
Kuaile Zhao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Risk Score ◽  
Squamous Cell ◽  
Immune Suppression ◽  
Risk Group ◽  
Lung Squamous Cell Carcinoma ◽  
High Risk Group ◽  
Low Risk

Abstract Background: Recent advances in immune checkpoint inhibitors (ICIs) have dramatically changed the therapeutic strategy against lung squamous cell carcinoma (LUSC). In the era of immunotherapy, effective biomarkers to better predict outcomes and inform treatment decisions for patients diagnosed with LUSC are urgently needed. We hypothesized that immune contexture of LUSC is potentially dictated by tumor intrinsic events, such as autophagy. Thus, we attempted to construct an autophagy-related risk signature and examine its prediction value for immune phenotype in LUSC.Method: The expression profile of LUSC was obtained from the cancer genome atlas (TCGA) database and the profile of autophagy-related genes (ARGs) was extracted. The survival‑related ARGs (sARGs) was screened out through survival analyses. Random forest was performed to select the sARGs and construct a prognostic risk signature based on these sARGs. The signature was further validated by receiver operating characteristic (ROC) analysis and Cox regression. GEO dataset was used as an independent testing dataset. Patients were divided into high-risk and low-risk group based on the risk score. Then, gene set enrichment analysis (GSEA) was conducted between the two groups. The Single-Sample GSEA (ssGSEA) was introduced to quantify the relative infiltration of immune cells. The correlations between risk score and several main immune checkpoints were examined. And the ESTIMATE algorithm was used to calculate the estimate/immune/stromal scores of the LUSC. Results: Four ARGs (CFLAR, RGS19, PINK1 and CTSD) with the most significant prognostic values were enrolled to construct the risk signature. Patients in high-risk group had better prognosis than the low-risk group (P < 0.0001 in TCGA; P < 0.01 in GEO) and considered as an independent prognosis factor. We also found that high-risk group indicated an immune-suppression status and had higher levels of infiltrating regulatory T cells and macrophages, which are correlated with worse outcome. Besides, risk score showed a significantly positive correlation with the expression of PD-1 and CTLA4, as well as estimate score and immune score.Conclusion: This study established a novel autophagy-related four-gene prognostic risk signature, and the autophagy-related scores are associated with immune landscape of LUSC, with higher score indicating a stronger immune-suppression status.

scholarly journals Evaluation of Histopathological Risk Model in a Cohort of Oral Squamous Cell Carcinoma Patients Treated with Accompanying Neck Dissection

2021 ◽  
Author(s):  
N. Rahman ◽  
B. Conn
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Neck Dissection ◽  
Risk Score ◽  
Squamous Cell ◽  
Risk Model ◽  
Nodal Metastasis ◽  
Low Risk ◽  
Term Survival

AbstractTo investigate the applicability of the validated histological risk model in a cohort of oral cavity squamous cell carcinoma patients treated concurrently with neck dissections. Primary tumours from 85 patients with primary excision of T1 and T2 Oral Squamous Cell Carcinomas (TNM 7th edition) including neck dissection were scored by three pathologists in consensus according to the validated risk model. The risk score data, along with traditional dataset values, were analysed to determine possible association with nodal metastasis and extracapsular spread. Seventy-two patients (54%) were classified with low or intermediate risk and 62 (46%) patients were ‘high risk’. A chi squared test showed that cases with nodal metastasis were highly statistically significant with the overall risk model score (X2 = 22.62 p = 0.0001). None of the neck dissections from tumours with low risk score showed evidence of metastasis (NPV = 100%) suggesting the risk score may also be a useful tool for predicting an absence of metastasis. Risk assessment of low-stage oral squamous cell carcinoma primary tumours may be predictive of the presence or absence of metastasis at presentation. Knowledge of the risk score and its constituent parts may inform treatment decisions at multidisciplinary meetings. Low risk squamous cell carcinoma may be a rare variant with low metastatic potential and excellent long-term survival.

scholarly journals Identification and Validation of a Hypoxia-Immune-Based Prognostic mRNA Signature for Oral Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Shaohua Lv ◽  
Jianhao Li ◽  
Songlin Piao ◽  
jichen Li
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Status ◽  
Cox Regression ◽  
Risk Group ◽  
Gene Signature ◽  
Low Risk

Abstract Background: Oral squamous cell carcinoma (OSCC) is a frequently encountered head and neck malignancy. Increasing evidence points towards an aberrant immune response and chronic cell hypoxia in the development of OSCC. However, there is a lack of a reliable hypoxia-immune-based gene signature that may serve to accurately prognosticate OSCC. Methods: The mRNA expression data of OSCC patients was extracted from the TCGA database. Hypoxia status was identified using the t-distributed Stochastic Neighbor Embedding (t-SNE) algorithm. Both ESTIMATE and single-sample gene-set enrichment analysis (ssGSEA) was used for further evaluation of immune status. The DEGs in different hypoxia and immune status were determined. A Machine learning method-Least Absolute Shrinkage and Selection operator (LASSO) Cox regression analysis allowed us to select prognostically significant hypoxia- and immune-related mRNAs in order to construct prognostic gene signature to predict the overall survival (OS) of OSCC patients. Results: A total of 773 DEGs were classified into either Hypoxia_High and Hypoxia_Low groups. Immune-associated DEG expressions were used to divide individuals into Immune_High, Immune_ Medium and Immune_Low groups. A total of 193 mRNAs which were significant in both immune function and hypoxia status were identified. With the Lasso Cox regression model, 8 signature mRNAs (FAM122C, RNF157, RANBP17, SOWAHA, KIAA1211, RIPPLY2, INSL3, and DNAH1) associated with OS were selected for further calculation of their respective risk scores. The risk score showed a significant association with age, perineural and lymphovascular invasion. In the GEO validation cohort, a better OS was observed in patients from the low-risk group in comparison to those in the high-risk group. High-risk patients also demonstrated different immune infiltration characteristics from the low-risk group. All individuals from the TCGA OSCC cohort showed similar trends in all 6 immune checkpoints, with those of the low-risk group yielding higher immune indicator scores in contrast to their high-risk counterparts. Conclusion: The hypoxia-immune-based gene signature has prognostic potential in OSCC.

Zinc α-2 Glycoprotein (ZAG) a Novel Biomarker for the Detection of Oral Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Mehwish Feroz Ali
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Malignant Lesion ◽  
Tobacco Consumption ◽  
Constant Stimulus ◽  
Dysplastic Lesion ◽  
Cancerous Lesion

Oral cancer, the most challenging and life threatening disease in the field of dentistry, may start as a reactive lesion due to constant stimulus from tobacco consumption, transform into a pre-malignant lesion (dysplastic lesion) and ultimately develop into a cancerous lesion (Invasive carcinoma). There is a fundamental revolution taking place in the analyzing methods; extraction of biological protein from the saliva rather than from tissues or blood. Several of the biomarkers have been studied with pro-carcinogenic effects like Interleukins (ILs), tumor necrosis factor (TNF) and leptin, but only a few have been stated in the literature, which show anti-cancer characteristics like adiponectin and zinc alpha-2 glycoprotein. This review explored the diagnostic and prognostic values of a biomarkers zinc alpha-2 glycoprotein (ZAG) in adults suspected of oral squamous cell carcinoma (OSCC). The PubMed, EMBASE and Google Scholar were searched for scientific studies reported on the potential mechanism of zinc alpha-2 glycoprotein. All the research articles were selected in which ZAG is applied solely or in conjunction with other biomarkers in oral cancer and other cancers. These literatures were carefully assessed to find out and compile the diagnostic and prognostic values and to inquire therapeutic action of ZAG in the process of carcinogenesis.

scholarly journals Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Wen Chen ◽  
Chenzhou Wu ◽  
Yafei Chen ◽  
Yuhao Guo ◽  
Ling Qiu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Endoplasmic Reticulum ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Endoplasmic Reticulum Stress ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Migration And Invasion ◽  
Ceramide Synthase

AbstractC18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma. However, the function of ceramide synthase 1, a key enzyme in C18 ceramide synthesis, in oral squamous cell carcinoma is still unclear. The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer. In this study, we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines. In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide, ceramide synthase 1 knockout was associated with the severity of oral malignant transformation. Immunohistochemical studies showed significant upregulation of PCNA, MMP2, MMP9, and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area. In addition, ceramide synthase 1 knockdown promoted cell proliferation, migration, and invasion in vitro. Overexpression of CERS1 obtained the opposite effect. Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation. Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation. In addition, mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance. Taken together, our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.

scholarly journals The REASON score: an epigenetic and clinicopathologic score to predict risk of poor survival in patients with early stage oral squamous cell carcinoma

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Chi T. Viet ◽  
Gary Yu ◽  
Kesava Asam ◽  
Carissa M. Thomas ◽  
Angela J. Yoon ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Risk Score ◽  
Squamous Cell ◽  
Early Stage ◽  
Genome Wide Association Studies ◽  
Gene Methylation ◽  
Poor Survival ◽  
Risk Of Death

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.

scholarly journals A prognostic model for stratification of stage IB/IIA esophageal squamous cell carcinoma: a retrospective study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lei-Lei Wu ◽  
Qi-Long Ma ◽  
Wei Huang ◽  
Xuan Liu ◽  
Li-Hong Qiu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Score ◽  
Training Group ◽  
Low Risk ◽  
Stage Ib ◽  
Ptnm Stage

Abstract Background To explore the postoperative prognosis of esophageal squamous cell carcinoma (ESCC) patients with stage IB/IIA, using a prognostic score (PS). Methods Stage IB/IIA ESCC patients who underwent esophagectomy from 1999 to 2010 were included. We retrospectively recruited 153 patients and extracted their medical records. Moreover, we analyzed the programmed death ligand-1 (PD-L1) expression of their paraffin tissue. The cohort were randomly divided into a training group (N = 123) and a validation group (N = 30). We selected overall survival (OS) as observed endpoint. Prognostic factors with a multivariable two-sided P < 0.05 met standard of covariate inclusion. Results Univariable and multivariable analyses identified pTNM stage, the number of lymph nodes (NLNs) and PD-L1 expression as independent OS predictors. Primary prognostic score which comprised above three covariates adversely related with OS in two cohorts. PS discrimination of OS was comparable between the training and internal validation cohorts (C-index = 0.774 and 0.801, respectively). In addition, the PS system had an advantage over pTNM stage in the identification of high-risk patients (C-index = 0.774 vs. C-index = 0.570, P < 0.001). Based on PS cutoff, training and validation datasets generated low-risk and high-risk groups with different OS. Our three-factor PS predicted OS (low-risk subgroup vs. high-risk subgroup 60-month OS, 74% vs. 23% for training cohort and 83% vs. 45% for validation cohort). Conclusion Our study suggested a PS for significant clinical stratification of IB/IIA ESCC to screen out subgroups with poor prognosis.

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