scholarly journals Multidimensional Mutational Profiling of the Indian HNSCC Sub-Population Provides IRAK1, a Novel Driver Gene and Potential Druggable Target

2021 ◽  
Vol 11 ◽  
Author(s):  
Sagar Sanjiv Desai ◽  
Raksha Rao K ◽  
Anika Jain ◽  
Pushpinder Singh Bawa ◽  
Priyatam Dutta ◽  
...  
Keyword(s):  
Head And Neck ◽  
Squamous Cell ◽  
Tumour Progression ◽  
Gene Prediction ◽  
Driver Gene ◽  
P Value ◽  
Tumour Suppressor Genes ◽  
Anatomical Site ◽  
Lasso Regression ◽  
Gene Signatures

Head and neck squamous cell carcinomas (HNSCC) include heterogeneous group of tumors, classified according to their anatomical site. It is the sixth most prevalent cancer globally. Among South Asian countries, India accounts for 40% of HNC malignancies with significant morbidity and mortality. In the present study, we have performed exome sequencing and analysis of 51 Head and Neck squamous cell carcinoma samples. Besides known mutations in the oncogenes and tumour suppressors, we have identified novel gene signatures differentiating buccal, alveolar, and tongue cancers. Around 50% of the patients showed mutation in tumour suppressor genes TP53 and TP63. Apart from the known mutations, we report novel mutations in the genes AKT1, SPECC1, and LRP1B, which are linked with tumour progression and patient survival. A highly curated process was developed to identify survival signatures. 36 survival-related genes were identified based on the correlation of functional impact of variants identified using exome-seq with gene expression from transcriptome data (GEPIA database) and survival. An independent LASSO regression analysis was also performed. Survival signatures common to both the methods led to identification of 4 dead and 3 alive gene signatures, the accuracy of which was confirmed by performing a ROC analysis (AUC=0.79 and 0.91, respectively). Also, machine learning-based driver gene prediction tool resulted in the identification of IRAK1 as the driver (p-value = 9.7 e-08) and also as an actionable mutation. Modelling of the IRAK1 mutation showed a decrease in its binding to known IRAK1 inhibitors.

Identification of Novel Prognosticators of Outcome in Squamous Cell Carcinoma of the Head and Neck

2004 ◽  
Vol 22 (19) ◽  
pp. 3965-3972 ◽  
Author(s):  
Volkert B. Wreesmann ◽  
Weiji Shi ◽  
Howard T. Thaler ◽  
Ashok Poluri ◽  
Dennis H. Kraus ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Chromosomal Aberrations ◽  
Univariate Analysis ◽  
Multiple Comparisons ◽  
Comparative Genomic ◽  
P Value ◽  
P Values

Purpose The goal of this study was to identify chromosomal aberrations associated with poor outcome in patients with head and neck squamous cell carcinoma (HNSCC). Patients and Methods We assessed the global genomic composition of 82 HNSCCs from previously untreated patients with comparative genomic hybridization (CGH). The CGH data were subcategorized into individual cytogenetic bands. Only genomic aberrations occurring in more than 5% of cases were analyzed, and redundancies were eliminated. Each aberration was submitted to univariate analysis to assess its relationship with disease-specific survival (DSS). We used Monte Carlo simulations (MCS) to adjust P values for the log-rank approximate χ2 statistics for each abnormality and further applied the Hochberg-Benjamini procedure to adjust the P values for multiple testing of the large number of abnormalities. We then submitted abnormalities whose univariate tests resulted in an adjusted P value of less than .15 together with significant demographic/clinical variables to stepwise Cox proportional hazards regression. We again verified and adjusted P values for the χ2 approximation of the final model by MCS. Results CGH analysis revealed a recurrent pattern of chromosomal aberrations typical for HNSCC. Univariate analysis revealed 38 abnormalities that were correlated with DSS. After controlling for multiple comparisons and confounding effects of stage, five chromosomal aberrations were significantly associated with outcome, including amplification at 11q13, gain of 12q24, and losses at 5q11, 6q14, and 21q11 (MCS adjusted P = .0009 to P = .01). Conclusion HNSCC contains a complex pattern of chromosomal aberrations. A sequential approach to control for multiple comparisons and effect of confounding variables allows the identification of clinically relevant aberrations. The significance of each individual abnormality merits further consideration.

scholarly journals Gene Expression Profiling and Clinicopathological Importance of Fer1L4 and DANCR Long Non Coding RNAs in Patients with Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Maryam Pirhoushiaran ◽  
Sara Hesami ◽  
Naeim Ehtesham ◽  
Saman Mehrabi ◽  
Reza Shirkoohi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Real Time ◽  
Squamous Cell ◽  
Roc Curve ◽  
Expression Profiling ◽  
Neck Squamous Cell Carcinoma ◽  
P Value ◽  
Diagnostic Power

Introduction: Head and Neck Squamous Cell Carcinoma (HNSCC) entails a heterogeneous group of tumours that emerge from the interaction between molecular changes and environmental factors. Dysregulated long noncoding RNAs (LncRNAs) play a major part in tumourigenesis and could be used as cancer biomarkers and therapeutic aims. Aim: To evaluate the expression of two lncRNAs named Fer-1 Like Family Member 4 (Fer1L4) and differentiation antagonising non protein-coding RNA (DANCR) in tumoural tissue of HNSCCs patients in comparison to Adjacent Non cancerous Tissues (ANCTs) to appraise their diagnostic power and the relationship with clinicopathological parameters. Materials and Methods: The present case-control study was designed, in which fresh frozen cancerous tissues and ANCTs were taken from 50 sporadic HNSCC patients who were attended in Imam Khomeini and Amir Alam Hospitals (Tehran, Iran) from from January to December 2019. Real-time PCR was utilised for expression profiling of Fer1L4 and DANCR. By employing GraphPad Prism 8.0 GraphPad Software, Inc., San Diego, CA, the real-time quantitative PCR experiments(2-..Ct) method and the Mann-Whitney test were exerted to analyse the obtained data. The Receiver Operating Characteristic (ROC) curve analysis was employed for figuring out the discrimination potential of two selected lncRNAs between the subject tumour and ANCT. Results: The expression of Fer1L4 was significantly down-regulated in tumoural tissues by analogy to ANCTs (p-value <0.0001) and statistically significant associations were found between the stage and grade status of the tumour with the relative expression of this lncRNA (p-value=0.008 and p-value=0.002 for stage and grade, respectively). The findings in this study indicated that the expression of DANCR was not statistically significant different in different tumoural tissues compared with ANCTs (p-value=0.46). ROC curve unraveled that the Fer1L4 had good diagnostic power Area Under Curve (AUC) 0.9252; p-value <0.0001. The expression of DANCR and Fer1L4 was significantly, respectively, higher and lower in samples with lymph node invasion and metastasis than that of the counterpart group. Concerning Human Papillomavirus (HPV) as an important exogenous factor for the development of HNSCC, DANCR and Fer1L4 were over-expressed and under- expressed, respectively in the HPV+group in comparison to HPV-. Conclusion: This work represented that Fer1L4 could be used as a novel diagnostic biomarker for HNSCC. In addition, the statistically significant difference in the expression of Fer1L4 and DANCR in metastatic tumours demonstrated that these two lncRNAs are promising targets for therapeutic purposes.

Serum levels of interleukins 4 and 10 in head and neck squamous cell carcinoma

2011 ◽  
Vol 126 (2) ◽  
pp. 175-179 ◽  
Author(s):  
Z Mojtahedi ◽  
B Khademi ◽  
A Yehya ◽  
A Talebi ◽  
M J Fattahi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Tumour Progression ◽  
Serum Levels ◽  
Interleukin 10 ◽  
Neck Squamous Cell Carcinoma ◽  
Interleukin 4 ◽  
Tumour Stage

AbstractObjective:There is currently controversy over the association between serum interleukin-4 and -10 levels and head and neck squamous cell carcinoma in patients of different ethnicity. This study aimed to investigate serum levels of these cytokines in Iranian patients with this pathology, and to analyse correlations with tumour location and tumour stage at diagnosis.Design:Serum cytokines levels were quantified using commercial enzyme-linked immunosorbent assays.Subjects:Study groups comprised 93 untreated patients and 53 healthy donors.Results:Serum interleukin-4 levels were significantly increased in patients compared with controls (p < 0.000), but were not significantly associated with tumour stage. Serum interleukin-10 levels were not raised in patients, nor associated with tumour stage.Conclusion:Serum levels of interleukin-4, but not -10, were increased in Iranian head and neck squamous cell carcinoma patients. These data do not support an association of these cytokines with tumour progression; this is consistent with previous findings.

Abstract 04: Caspase-8 is a novel candidate driver gene in head and neck squamous cell carcinoma

2017 ◽  
Author(s):  
Burak Uzunparmak ◽  
Antje Lindemann ◽  
Mitchell J. Frederick ◽  
Jeffrey N. Myers ◽  
Curtis R. Pickering
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Driver Gene ◽  
Caspase 8

scholarly journals Impact of p16 Status and Anatomical Site in Anti-PD-1 Immunotherapy-Treated Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Patients

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4861
Author(s):  
Kate Clancy ◽  
Chelsea S. Hamill ◽  
Wendi Q. O’Neill ◽  
Brandon Vu ◽  
Jason Thuener ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Medical Center ◽  
Academic Medical Center ◽  
Neck Squamous Cell Carcinoma ◽  
Anatomical Site ◽  
Clinical Practices ◽  
The Impact

In head and neck squamous cell carcinoma (HNSCC), anti-PD-1 inhibitors are approved for recurrent/metastatic (R/M) disease and anticipated to expand to other indications. The impact of p16 status and anatomical site on overall survival (OS) in immunotherapy-treated HNSCC patients remains unresolved. We performed a retrospective analysis of R/M HNSCC patients receiving anti-PD-1 immunotherapy at our academic medical center with an extensive community satellite network. Fifty-three R/M HNSCC patients were treated with anti-PD-1 immunotherapy and had a median OS of 6 months. Anatomical site was associated with distinct OS; oropharynx and larynx patients have superior OS compared to oral cavity patients. Analysis of the OPSCC subset showed p16+ status as a favorable, independent prognostic biomarker (HR 7.67 (1.23–47.8); p = 0.029). Further studies to assess the link between anatomical site, p16 status, and anti-PD-1 treatment outcomes in large cohorts of R/M HNSCC patients managed in real-world clinical practices and clinical trials should be prioritized.

Novel biomarkers for head and neck squamous cell carcinoma: A retrospective study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18010-e18010
Author(s):  
Shengjin Dou ◽  
Lin Zhang ◽  
Rongrong Li ◽  
Debin Sun ◽  
Lijia Wu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Treatment Group ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Clinical Benefit ◽  
P Value ◽  
Egfr Amplification ◽  
Ccnd1 Amplification ◽  
The Difference

e18010 Background: PDL-1 and tumor mutation burden are only useful to select a small portion of patients with head and neck squamous cell carcinoma for immunotherapy, more biomarkers are in an urgent need for the majority. Methods: Ninety-nine recurrent/metastatic patients were analyzed. PD-1 cohort including 78 patients; Non-PD-1(NPD-1) cohort including 28 patients received anti-EGFR antibody and harbored at least one of EGFR amplification/mutation, CCND1 amplification, FGF3/4/19 amplification, or CDKN2A/B mutations (including 7 patients received with both treatment). Patients were evaluated as no clinical benefit (NCB) if experiencing progressive disease or stable disease lasting < 6 months and were discontinued from immunotherapy within 3 months; otherwise, patients were evaluated as clinical benefit (CB). Tumor genomic DNA was isolated from formalin-fixed paraffin-embedded tissue for the targeted sequencing by a 769-gene panel. R package was used for fisher test to evaluate the variants. p < 0.05 was set as significant. Results: With median age of 57 years old, this study included 75 (75.8%) oral squamous cell carcinoma patients,17 (17.2%) oropharyngeal carcinoma patients and 7 others. Sixty-nine (69.7%) patients have PD-L1 CPS≥1, 27 (27.3%) patients have CPS＜1 and 3 (3.0%) have an unknown CPS. The estimated 10-month progression-free survival of the NPD-1 cohort and PD-1cohort were 60.0%and 47.6% (p = 0.06) respectively. In NPD-1 cohort, 23 patients were evaluated as CB (78.3%), and in PD-1 cohort, 41 were evaluated as CB (52.6%) (p = 0.00682), indicating EGFR amplification/mutation, CCND1 amplification, FGF3/4/19 amplification, or CDKN2A/B mutations may be negatively correlated with immunotherapies. There were 14 patients who harbored either EGFR amplification or SNV mutation. Of the 8 patients who received NPD-1 treatment, 7 were CB (87.5%); Of the 8 patients who received PD-1 treatment, 2 were CB (25%) Statistically, the difference between NPD-1 treatment group and PD-1 treatment group was significant with a p value of 0.04056. There were 16 patients who harbored CCND1 amplification, or FGF3/4/19 amplification. Of the 12 patients who received NPD-1 treatment, 10 were evaluated as CB (83.3%); Of the 7 patients who received PD-1 treatment, 1 was evaluated as CB (14.3%). The difference was significant with a p value of 0.00627. There were 44 patients who obtained CDKN2A/B mutations. Of the 12 patients who received NPD-1 treatment, 11 acquired CB (81.7%); Of the 33 patients who received PD-1 treatment, 18 acquired CB (54.5%). The difference was significant with a p value of 0.03325. Conclusions: We for the first time showed that genetic-altered EGFR, FGF3/4/19, CCND1 and CDKN2A/B were negatively correlated with anti-PD-1 therapy in clinical cohorts retrospectively and these genetic aberrations may serve as novel immune-negative biomarkers for immunotherapies.

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