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.

Association of serum level of YKL-40 in patients with squamous cell carcinoma of the head and neck with survival

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5551-5551
Author(s):  
A. Roslind ◽  
J. S. Johansen ◽  
I. J. Christensen ◽  
J. Bentzen ◽  
D. L. Nielsen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Small Cell Lung Carcinoma ◽  
Univariate Analysis ◽  
High Serum ◽  
Cell Lung Carcinoma ◽  
Stage 1

5551 Background: High serum YKL-40 is associated with poor prognosis in breast-, colorectal-, ovarian-, prostate-, small cell lung carcinoma and malignant melanoma. YKL-40 is secreted by cancer cells, macrophages and neutrophils. Its function in cancer is unknown. It may be a growth factor, play a role in angiogenesis or protect against apoptosis. The aim was to examine serum YKL-40 in patients with squamous cell carcinoma of the head and neck (SCCHN). Methods: YKL-40 was determined by ELISA (Quidel, Santa Clara, CA) in serum samples from 138 patients with SCCHN (median age 60, range 44–92 years) before surgery and/or fractionated radiotherapy (total dose of 60–68 Gy, 2-Gy fractions). 42 patients had stage 1, 28 stage 2, 22 stage 3, and 46 stage 4 disease. The median follow-up time was 4.0 years (range 15 days–8.5 years). 91 patients had died. Results: Serum YKL-40 was increased (p < 0.001) in patients with SCCHN (median 120 μg/l, range 25–1848 μg/l) compared to healthy controls (43 μg/l, 20–184 μg/l, n = 245). Serum YKL-40 was elevated in 52% of the patients. Patients with stage 1 disease had lower, but non-significant, serum YKL-40 compared to patients with stage 2–4 disease (median 113 μg/l, range 25–1000 μg/l vs. 139 μg/l, 29–1848 μg/l, p = 0.06). Patients with high serum YKL-40 had significantly shorter survival than patients with normal serum YKL-40 (33 months vs. 74 months, p = 0.01 logrank test). Univariate analysis of serum YKL-40 (log transformed and treated as a continuous covariate) showed significant association with overall survival after start of therapy (HR = 1.4, 95% CI: 1.2–1.7, p = 0.0004). Multivariate Cox analysis including age, stage and serum YKL-40 (log transformed and treated as a continuous variable) showed that stage (stage 3–4 vs. stage 1–2, HR = 3.0, 95% CI: 1.9–4.6, p < 0.0001) and serum YKL-40 (HR = 1.5, 95% CI: 1.2–1.8, p = 0.0003) were independent prognostic variables of overall survival. Conclusions: Serum YKL-40 is a prognostic biomarker of overall survival in SCCHN patients. No significant financial relationships to disclose.

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.

Detection of chromosomal aberrations in cytologic brush specimens from head and neck squamous cell carcinoma

Cancer ◽  
1997 ◽  
Vol 81 (5) ◽  
pp. 309-314 ◽  
Author(s):  
Joris A. Veltman ◽  
Anton H.�N. Hopman ◽  
Fredrik J. Bot ◽  
Frans C.�S. Ramaekers ◽  
Johannes J. Manni
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Chromosomal Aberrations ◽  
Neck Squamous Cell Carcinoma

A comparative study of monoclonal antibody against EGFR (nimotuzumab) used in combination with chemoradiation versus chemoradiation alone in the treatment of locally advanced inoperable squamous cell carcinoma of the head and neck.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16012-e16012
Author(s):  
Aseem Rai Bhatnagar ◽  
Dharam Pal Singh ◽  
Rameshwaram Sharma ◽  
Om Prakash Sharma ◽  
Shantanu Sharma ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Tumor Response ◽  
Locally Advanced ◽  
Acute Radiation ◽  
P Value ◽  
Significant Difference

e16012 Background: To determine the efficacy, safety and tolerability of concurrent Nimotuzumab (monoclonal antibody against epidermal growth factor receptor) used in combination with chemoradiation versus chemoradiation (CRT) alone in advanced inoperable squamous cell carcinoma of the head and neck (SCCHN). Methods: 56 patients were randomly assigned to either of the two treatment arms, nimotuzumab + CRT arm and CRT alone arm. Both arms received concurrent cisplatin 30 mg/m2 repeated weekly for 6-7 cycles along with external beam radiotherapy 64-70 Gy (200cGy/day for 5 days a week for 6-7 weeks). Nimotuzumab arm additionally received nimotuzumab 200 mg weekly for 6-7 cycles. The patients were followed for 6 months after completion of CRT. The study end points were tumor response evaluation according to the RECIST Criteria version 1.1 and safety analysis using RTOG Acute Radiation Morbidity Scoring Criteria. Patients were evaluated weekly with hematologic tests and for adverse events like mucositis and dermatitis during the CRT. Tumor assessment was performed with clinical and endoscopic methods regularly during the CRT and then at 1 month, 3 month and 6 month interval after CRT. One MR imaging was done before starting the CRT to evaluate the baseline tumor characteristics and another was done after the completion of CRT either at 3 months or 6 months or at both the intervals. Results: 25 patients each were evaluable in both the arms who completed the 6 months study. The overall response rate (complete response + partial response) was 96% in Nimotuzumab + CRT arm whereas it was only 72% in CRT alone arm after 6 months of completion of CRT, which is statistically significant (p-value = 0.0206 by chi square test). Additionally, nimotuzumab did not potentiate toxicities of CRT and there was no significant difference in the acute radiation mucositis, dermatitis or hematological toxicities in both the groups (p-value>>0.05). Conclusions: Nimotuzumab can be safely added to the standard CRT treatment for advanced inoperable SCCHN, to achieve better tumor response without potentiating toxicity.

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