Dataset Information

CENP-A Subnuclear Localization Pattern as Marker Predicting Curability by Chemoradiation Therapy for Locally Advanced Head and Neck Cancer Patients.

ABSTRACT: Effective biomarkers predictive of the response to treatments are key for precision medicine. This study identifies the staining pattern of the centromeric histone 3 variant, CENP-A, as a predictive biomarker of locoregional disease curability by chemoradiation therapy. We compared by imaging the subnuclear distribution of CENP-A in normal and tumoral tissues, and in a retrospective study in biopsies of 62 locally advanced head and neck squamous cell carcinoma (HNSCC) patients treated by chemoradiation therapy. We looked for predictive factors of locoregional disease control and patient's survival, including CENP-A patterns, Ki67, HPV status and anisokaryosis. In different normal tissues, we reproducibly found a CENP-A subnuclear pattern characterized by CENP-A clusters both localized at the nuclear periphery and regularly spaced. In corresponding tumors, both features are lost. In locally advanced HNSCC, a specific CENP-A pattern identified in pretreatment biopsies predicts definitive locoregional disease control after chemoradiation treatment in 96% (24/25) of patients (OR = 17.6 CI 95% [2.6; 362.8], p = 0.002), independently of anisokaryosis, Ki67 labeling or HPV status. The characteristics of the subnuclear pattern of CENP-A in cell nuclei revealed by immunohistochemistry could provide an easy to use a reliable marker of disease curability by chemoradiation therapy in locally advanced HNSCC patients.

SUBMITTER: Verrelle P

PROVIDER: S-EPMC8391827 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CENP-A Subnuclear Localization Pattern as Marker Predicting Curability by Chemoradiation Therapy for Locally Advanced Head and Neck Cancer Patients.

Verrelle Pierre P Meseure Didier D Berger Frédérique F Forest Audrey A Leclère Renaud R Nicolas André A Fortas Emilie E Sastre-Garau Xavier X Lae Marick M Boudjemaa Sabah S Mbagui Rodrigue R Calugaru Valentin V Labiod Dalila D De Koning Leanne L Almouzni Geneviève G Quivy Jean-Pierre JP

Cancers 20210804 16

Effective biomarkers predictive of the response to treatments are key for precision medicine. This study identifies the staining pattern of the centromeric histone 3 variant, CENP-A, as a predictive biomarker of locoregional disease curability by chemoradiation therapy. We compared by imaging the subnuclear distribution of CENP-A in normal and tumoral tissues, and in a retrospective study in biopsies of 62 locally advanced head and neck squamous cell carcinoma (HNSCC) patients treated by chemora ...[more]

PMID: 34439087

Similar Datasets

Project description:BackgroundCisplatin-based chemoradiation (CCRT) offers locally advanced head and neck squamous cell carcinoma (LAHNSCC) patients high local control rate, however, relapses are frequent. Our goal was to evaluate if association of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, with CCRT improved response rate (RR) and associated biomarkers.MethodsThis phase II trial included patients with unresectable locally advanced (LA) oropharynx (OP) squamous cell carcinoma. CCRT began after 2 weeks of VPA (P1). Primary goal was RR at 8 weeks after chemoradiation (CRT)+VPA (P2). Biomarkers included microRNA (miR) polymerase chain reaction (PCR)-array profiling in plasma compared to healthy controls by two-sample t-test. Distribution of p-values was analysed by beta-uniform mixture. Findings were validated by real-time PCR quantitative polymerase chain reaction (qPCR) for selected miRs in plasma and saliva. p16, HDAC2 and RAD23 Homolog B, Nucleotide Excision Repair Protein (HR23B) tumour immunohistochemistry were evaluated.ResultsGiven significant toxicities, accrual was interrupted after inclusion of ten LA p16 negative OP patients. All were male, smokers/ex-smokers, aged 41-65 and with previous moderate/high alcohol intake. Nine evaluable patients yielded a RR of 88%. At false discovery rate of 5%, 169 miRs were differentially expressed between patients and controls, including lower expression of tumour suppressors (TSs) such as miR-31, -222, -let-7a/b/e and -145. miR-let-7a/e expression was validated by qPCR using saliva. A HDAC2 H-score above 170 was 90% accurate in predicting 6-month disease-free survival.ConclusionsVPA and CRT offered high RR; however, with prohibitive toxicities, which led to early trial termination. Patients and controls had a distinct pattern of miR expression, mainly with low levels of TS miRs targeting Tumor protein P53 (TP53). miR-let-7a/e levels were lower in patients compared to controls, which reinforces the aggressive nature of such tumours (NCT01695122).

Project description:ImportanceNational Comprehensive Cancer Network guidelines recommend weekly cisplatin as an alternative concurrent systemic therapy for definitive chemoradiation in patients with head and neck cancer. However, the impact of different levels of adherence to weekly cisplatin on outcomes stratified by human papillomavirus p16 status remains unclear.ObjectiveTo evaluate the association between the number of weekly cisplatin cycles and outcomes.Design, setting, and participantsThis retrospective, observational, single-institution cohort study at The Ohio State Comprehensive Cancer Center included patients with a diagnosis of nonmetastatic head and neck cancer between December 1, 2011, and March 30, 2020, who received chemoradiation. Data analysis was performed between March and May 2024.ExposureA total of 5, 6, or 7 to 8 weekly cisplatin cycles.Main outcomes and measuresThe primary outcomes were overall survival (OS), progression-free survival (PFS), locoregional failure (LRF), and distant failure (DF). Cox multivariable analysis was performed for variables associated with OS and PFS, and Fine-Gray multivariable analysis was performed for variables associated with LRF and DF.ResultsA total of 142 patients met the criteria (119 men [83.8%]; median [IQR] age, 59 [54-63] years). Median (IQR) follow-up was 46.8 (40.8-55.6) months. Among 92 patients with reasons for cisplatin interruption reported, the most common reason was low blood counts (42 patients [45.7%]). Those who missed weekly cisplatin cycles had worse OS (adjusted hazard ratio [aHR], 2.22; 95% CI, 1.19-4.17; P = .01) and PFS (aHR, 1.83; 95% CI, 1.06-3.15; P = .03) than those who received 7 to 8 cycles. Cancer control outcomes were comparable between these groups (LRF aHR, 0.53; 95% CI, 0.15-1.93; P = .34; DF aHR, 1.51; 95% CI, 0.60-3.82; P = .38). Patients with p16-negative tumors who missed weekly cisplatin cycles had worse OS (for every missing cisplatin cycle, aHR, 11.34, 1.51-84.94; P = .02) than those treated with 7 to 8 cycles. However, for those with p16-positive tumors, there were no statistically significant differences in OS between those who missed weekly cisplatin cycles vs others who received 7 to 8 cycles (aHR, 1.21; 95% CI, 0.47-3.14; P = .69).Conclusions and relevanceIn this cohort study of patients with head and neck cancer who received definitive chemoradiation, those with p16-negative tumors who missed weekly cisplatin cycles had lower OS than those who received 7 to 8 cycles, although OS was comparable between these groups for p16-positive tumors. Cytopenia represented the most common reason for cisplatin interruption.

Dataset Information

CENP-A Subnuclear Localization Pattern as Marker Predicting Curability by Chemoradiation Therapy for Locally Advanced Head and Neck Cancer Patients.

Publications

CENP-A Subnuclear Localization Pattern as Marker Predicting Curability by Chemoradiation Therapy for Locally Advanced Head and Neck Cancer Patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets