Molecular prediction of adjuvant cisplatin efficacy in Non-Small Cell Lung Cancer (NSCLC)—validation in two independent cohorts
| Autor: | Anker Jon Hansen, Peter Buhl Jensen, Thomas Jensen, Jesper Ravn, Jon Askaa, Steen Knudsen, Eric Santoni-Rugiu, Jens Benn Sørensen, Ib Jarle Christensen, Ida Kappel Buhl, Bruce Pratt |
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| Jazyk: | dánština |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Oncology Lung Neoplasms medicine.medical_treatment Carcinoma Cells Cancer Treatment Datasets as Topic lcsh:Medicine non-small cell lung cancer (NSCLC) Biochemistry Lung and Intrathoracic Tumors Cohort Studies 0302 clinical medicine Carcinoma Non-Small-Cell Lung Antineoplastic Combined Chemotherapy Protocols Medicine and Health Sciences lcsh:Science Randomized Controlled Trials as Topic Cultured Tumor Cells Aged 80 and over Multidisciplinary Hazard ratio Squamous Cell Carcinomas Middle Aged Prognosis Nucleic acids Gene Expression Regulation Neoplastic Treatment Outcome Molecular Diagnostic Techniques Chemotherapy Adjuvant 030220 oncology & carcinogenesis Female Biological Cultures Anatomy Research Article medicine.drug Adult medicine.medical_specialty Histology Research and Analysis Methods Vinorelbine Carcinomas 03 medical and health sciences Breast cancer Cell Line Tumor Internal medicine Genetics Biomarkers Tumor medicine Carcinoma Humans Non-coding RNA Aged Cisplatin Chemotherapy business.industry lcsh:R Cancers and Neoplasms Biology and Life Sciences Cancer Cell Cultures medicine.disease Non-Small Cell Lung Cancer Gene regulation MicroRNAs 030104 developmental biology RNA lcsh:Q Gene expression Transcriptome business Biomarkers |
| Zdroj: | Buhl, I K, Santoni Rugiu, E, Ravn, J, Hansen, A, Christensen, I J, Jensen, T, Pratt, B, Askaa, J, Jensen, P B, Knudsen, S & Sørensen, J B 2018, ' Molecular prediction of adjuvant cisplatin efficacy in Non-Small Cell Lung Cancer (NSCLC)—validation in two independent cohorts ', PLOS ONE, bind 13, nr. 3, e0194609 . https://doi.org/10.1371/journal.pone.0194609 PLoS ONE, Vol 13, Iss 3, p e0194609 (2018) PLoS ONE |
| Popis: | IntroductionEffective predictive biomarkers for selection of patients benefiting from adjuvant platinum-based chemotherapy in non-small cell lung cancer (NSCLC) are needed. Based on a previously validated methodology, molecular profiles of predicted sensitivity in two patient cohorts are presented.MethodsThe profiles are correlations between in vitro sensitivity to cisplatin and vinorelbine and baseline mRNA expression of the 60 cell lines in the National Cancer Institute panel. An applied clinical samples filter focused the profiles to clinically relevant genes. The profiles were tested on 1) snap-frozen tumors from 133 patients with completely resected stage 1B-2 NSCLC randomized to adjuvant cisplatin and vinorelbine (ACV, n = 71) or no adjuvant treatment (OBS, n = 62) and 2) formalin-fixed paraffin-embedded (FFPE) tumors from 95 patients with completely resected stage 1A-3B NSCLC receiving adjuvant cisplatin and vinorelbine.ResultsThe combined cisplatin and vinorelbine profiles showed: 1) univariate Hazard Ratio (HR) for sensitive versus resistant of 0.265 (95% CI:0.079–0.889, p = 0.032) in the ACV cohort and a HR of 0.28 in a multivariate model (95% CI:0.08–1.04, p = 0.0573); 2) significant prediction at 3 year survival from surgery in univariate (HR = 0.138 (95% CI:0.035–0.537), p = 0.004) and multivariate analysis (HR = 0.14 (95% CI:0.030–0.6), p = 0.0081). No discrimination was found in the OBS cohort (HR = 1.328, p = 0.60). The cisplatin predictor alone had similar figures with 1) univariate HR of 0.37 (95% CI:0.12–1.15, p = 0.09) in the ACV cohort and 2) univariate HR of 0.14 (95% CI:0.03–0.59, p = 0.0076) to three years. Functional analysis on the cisplatin profile revealed a group of upregulated genes related to RNA splicing as a part of DNA damage repair and apoptosis.ConclusionsProfiles derived from snap-frozen and FFPE NSCLC tissue were prognostic and predictive in the patients that received cisplatin and vinorelbine but not in the cohort that did not receive adjuvant treatment. |
| Databáze: | OpenAIRE |
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