Something for Everyone From Low-Risk to High-Risk: 5 Recent Studies to Improve Treatment and Surveillance for All Patients With Squamous Cell Carcinoma of the Head and Neck

2021 ◽  
Vol 111 (1) ◽  
pp. 1-8
Author(s):  
Michelle Mierzwa ◽  
Beth M. Beadle ◽  
Melvin L.K. Chua ◽  
Daniel J. Ma ◽  
David J. Thomson ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Low Risk ◽  
Improve Treatment

scholarly journals An Immune-associated lncRNA Signature Predicts the Survival of Patients With Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Jian Wang ◽  
Qinjiang Bian ◽  
Jialin Liu ◽  
Lijuan Du ◽  
Adili Moming
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Operating Characteristic ◽  
Low Risk ◽  
Neck Squamous Cell Carcinoma ◽  
Differentially Expressed ◽  
Risk Scores

Abstract BackgroundThe malignant progression and treatment resistance of head and neck squamous cell carcinoma are closely related to the tumor immune microenvironment. Long non-coding RNA (lncRNA) plays a regulatory role in this process and may be exploited as new signatures for head and neck squamous cell carcinoma(HNSCC) diagnosis, prognosis, and treatment.MethodsHNSCC transcriptome data was abstracted from the Cancer Genome Atlas (TCGA) data resource, and uncovered immune-linked lncRNA through co-expression analysis. Besides, univariate along with Lasso penalty regression were employed to determine immune-linked lncRNA pairs with different expressions. We then compared area under the curve, calculated the Akaike information criterion (AIC) value of the receiver operating characteristic curve for 5 years, determined cutoff points, and established an optimal predictive model for identifying high- and low-risk HNSCC patients. Then, we evaluated these patients with high- and low-risk HNSCC in terms of survival, clinic-pathological characteristics, tumor-infiltrating immune cells, chemotherapeutic efficacy, and immunosuppressed biomarkers.ResultsThis study included 545 samples. By co-expression analysis of known immune-linked genes and lncRNAs, a total of 809 immune-related lncRNAs were collected. 77 differentially expressed immune-related lncRNAs were identified (logFC>2,FDR<0.01). The identified differentially-expressed immune-linked lncRNAs were used to develop differential immune-linked lncRNA pairs. Univariate and modified Lasso regression analysis identified 40 differentially expressed immune linked lncRNAs pairs, 17 of which were incorporated in the Cox proportional hazard model by a stepwise approach. The signature could well predict the survival of patients, and the area under the receiver operating characteristic (ROC) of 17 lncRNA pairs predicted 1, 3, and 5-year survival rates (AUC) were all greater than 0.74. Kaplan-Meier analysis found that patients at low risk had longer survival than those in the high-risk group (p<.001). In addition, T stage, survival status, N stage, and clinical stage, were remarkably linked to the risk. The high- and low risk groups were correlated with tumor invading immune cells like macrophages, CD8+ T-cells, monocytes, along with CD4+ T-cells. ICI-related biomarker correlation analysis showed high risk scores were positively linked to high CDK8 expression (p<0.001) and negatively correlated with BTLA , LAG3 and PDCD1 (p<0.001). High-risk scores were correlated with lower IC50 for chemotherapeutics like Docetaxel (p<0.01), indicating that this model can predict chemotherapeutic efficacy.ConclusionsOur results offer promising prospects for identifying innovative molecular targets of immunotherapy and to improve therapeutic approaches for head and neck squamous cell carcinoma patients.

Development and Validation of a Hypoxia-Related Gene Pairs Signature to Predict Overall Survival in Head and Neck Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Zhao Ding ◽  
Hefeng Li ◽  
Deshun Yu
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cells ◽  
High Risk ◽  
Gene Silencing ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Poor Prognosis ◽  
Risk Group ◽  
Low Risk

Abstract Objective Head and neck squamous cell carcinoma (HNSCC) are a highly aggressive tumor with an extremely poor prognosis. Thus, we aimed to develop and validate a robust prognostic signature that can estimate the prognosis for HNSCC.Methods Data on gene expressions and clinical were downloaded from TCGA and GEO database. To develop the best prognosis signature, a LASSO Cox Regression model was employed. Time-dependent receiver-operating characteristic (ROC) was used to determine the best cut-off value. Patients were divided into high-risk and low-risk hypoxia groups according to cut-off value. Survival differences were evaluated by log-rank test, while multivariate analysis was performed by a Cox proportional hazards model.Results A 17-HRGPs composed of 24 unique genes was constructed, which was significantly related to OS. In the TCGA and GEO datasets, patients in the high hypoxia risk group have a poor prognosis (TCGA: P < 0.001, GEO: P < 0.05). After adjusting for other clinicopathological parameters, the 17-HRGP signature was independent prognostic factors in patients with HNSCC (P < 0.05). Functional analysis revealed that mRNA binding, gene silencing by RNA, RNA binding involved in posttranscriptional gene silencing signaling pathway were enriched in the low-risk groups. For this model, C-index was 0.684, which was higher than that of many established risk models. Macrophages M0, Mast cells activated, NK cells resting, and T cells CD4 memory resting, etc. were significantly higher in the high-risk group, and B cells memory, Plasma cells, T cells follicular helper, T cells gamma delta, and T cells CD8, etc. were significantly higher in the low-risk group.Conclusion In summary, our study constructed a robust HRGPs signature as molecular markers for predicting the outcome of HNSCC patients.

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.

scholarly journals p16 expression in cutaneous squamous cell carcinoma of the head and neck is not associated with integration of high risk HPV DNA or prognosis

Pathology ◽  
2017 ◽  
Vol 49 (5) ◽  
pp. 494-498 ◽  
Author(s):  
Laveniya Satgunaseelan ◽  
Noel Chia ◽  
Hyerim Suh ◽  
Sohaib Virk ◽  
Bruce Ashford ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Hpv Dna ◽  
High Risk Hpv ◽  
P16 Expression

scholarly journals A TP53 mutation model for the prediction of prognosis and therapeutic responses in head and neck squamous cell carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Congyu Shi ◽  
Shan Liu ◽  
Xudong Tian ◽  
Xiaoyi Wang ◽  
Pan Gao
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Risk Score ◽  
Squamous Cell ◽  
Risk Group ◽  
High Risk Group ◽  
Mutation Model ◽  
Therapeutic Responses

Abstract Background Tumor protein p53 (TP53) is the most frequently mutated gene in head and neck squamous cell carcinoma (HNSC), and TP53 mutations are associated with inhibited immune signatures and poor prognosis. We established a TP53 mutation associated risk score model to evaluate the prognosis and therapeutic responses of patients with HNSC. Methods Differentially expressed genes between patients with and without TP53 mutations were determined by using data from the HNSC cohort in The Cancer Genome Atlas database. Patients with HNSC were divided into high- and low-risk groups based on a prognostic risk score that was generated from ten TP53 mutation associated genes via the multivariate Cox regression model. Results TP53 was the most common mutant gene in HNSC, and TP53 mutations were associated with immunogenic signatures, including the infiltration of immune cells and expression of immune-associated genes. Patients in the high-risk group had significantly poorer overall survival than those in the low-risk group. The high-risk group showed less response to anti-programmed cell death protein 1 (PD-1) therapy but high sensitivity to some chemotherapies. Conclusion The risk score based on our TP53 mutation model was associated with poorer survival and could act as a specific predictor for assessing prognosis and therapeutic response in patients with HNSC.

scholarly journals Identification of Expression Patterns and Potential Prognostic Significance of m5C-Related Regulators in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhenyuan Han ◽  
Biao Yang ◽  
Yu Wang ◽  
Xiuxia Zeng ◽  
Zhen Tian
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Expression Patterns ◽  
Critical Role ◽  
Low Risk ◽  
Neck Squamous Cell Carcinoma ◽  
Differentially Expressed ◽  
Rna Modification

5-Methylcytosine (m5C) methylation is a major epigenetic technique of RNA modification and is dynamically mediated by m5C “writers,” “erasers,” and “readers.” m5C RNA modification and its regulators are implicated in the onset and development of many tumors, but their roles in head and neck squamous cell carcinoma (HNSCC) have not yet been completely elucidated. In this study, we examined expression patterns of core m5C regulators in the publicly available HNSCC cohort via bioinformatic methods. The differentially expressed m5C regulators could divide the HNSCC cohort into four subgroups with distinct prognostic characteristics. Furthermore, a three-gene expression signature model, comprised of NSUN5, DNMT1, and DNMT3A, was established to identify individuals with a high or low risk of HNSCC. To explore the underlying mechanism in the prognosis of HNSCC, screening of differentially expressed genes, followed by the analysis of functional and pathway enrichment, from individuals with high- or low-risk HNSCC was performed. The results revealed a critical role for m5C RNA modification in two aspects of HNSCC: (1) dynamic m5C modification contributes to the regulation of HNSCC progression and (2) expression patterns of NSUN5, DNMT1, and DNMT3A help to predict the prognosis of HNSCC.

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.

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