Anca Nastase1, Simona O Dima1, Audrey Lupo2, Victoria Laszlo1, Rebecca Tagett3, Sorin Draghici1, Monica Elia Georgescu4, Alexandru Nechifor4, Sorin Berbece4, Irinel Popescu1, Marco Alifano2, Walter Klepetko5, Madalina Grigoroiu6. 1. Center of Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania. 2. Hôpital Cochin, AP-HP, Université de Paris, Paris, France. 3. Intelligent Systems and Bioinformatics Laboratory (ISBL), Department of Computer Science, Wayne State University, Detroit, MI, U.S.A. 4. Dunarea De Jos University, Faculty of Medicine and Pharmacy, Galati, Romania. 5. Department of Thoracic Surgery, Vienna General Hospital, Vienna, Austria. 6. Center of Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania; madalina.grigoroiu@gmail.com.
Abstract
BACKGROUND: Survival rates among non-small cell lung cancer (NSCLC) stage IIIA (N2) patients are generally low and depend on the treatment. PATIENTS AND METHODS: We aimed to identify predictive markers for long term survival in responders and non-responders to chemotherapy, analyzing tumour and non-tumour samples by microarray (n=35) and whole exome sequencing (WES, n=25). RESULTS: WES data showed correlation of overall survival of all patients with rs9905892 in the SLFN12L gene. High frequency of mutations (4/6, 66.7%) was identified in members of SWI/SNF complex in responder patients and in patients that were alive after seven years. Microarray data for immune components showed that VISTA (VSIR) was down-regulated in tumoral tissue. CONCLUSION: Our research suggests that mutations in SWI/SNF complex associate with long term survival after multimodal treatment, while down-regulation of VISTA might indicate its immunomodulatory role in NSCLC stage III (N2) patients.
BACKGROUND: Survival rates among non-small cell lung cancer (NSCLC) stage IIIA (N2) patients are generally low and depend on the treatment. PATIENTS AND METHODS: We aimed to identify predictive markers for long term survival in responders and non-responders to chemotherapy, analyzing tumour and non-tumour samples by microarray (n=35) and whole exome sequencing (WES, n=25). RESULTS: WES data showed correlation of overall survival of all patients with rs9905892 in the SLFN12L gene. High frequency of mutations (4/6, 66.7%) was identified in members of SWI/SNF complex in responder patients and in patients that were alive after seven years. Microarray data for immune components showed that VISTA (VSIR) was down-regulated in tumoral tissue. CONCLUSION: Our research suggests that mutations in SWI/SNF complex associate with long term survival after multimodal treatment, while down-regulation of VISTA might indicate its immunomodulatory role in NSCLC stage III (N2) patients.
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