Background/Aim: Patients with stage IIIA (N2) non-small cell lung cancer (NSCLC) with no progression after induction chemotherapy are usually selected for surgery. Nowadays, response to chemotherapy is not predictable. We aimed to identify genomic predictive markers for response to induction chemotherapy in stage IIIA (N2) NSCLC patients. Patients and Methods: Whole-exome sequencing (WES) was performed on samples from 11 patients with no response after induction chemotherapy and 6 patients with documented pathological response, admitted to the

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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.Patients with stage IIIA (N2) non-small cell lung cancer (NSCLC) are a heterogeneous group. Ruckdeschel et al. (1) divides these patients into three groups: N2 lymph nodes with minimum or microscopic invasion, randomly detected during or after surgical intervention; N2 lymph nodes detected before the surgical intervention either by imaging or surgery, and patients with massive N2 lymph nodes from multiple lymph node stations. Several treatment strategies have been suggested for stage IIIA NSCLC patients during the past two decades (2), including chemotherapy or neoadjuvant chemoradiotherapeutic treatment followed by surgery, primary surgery followed by adjuvant chemotherapy, with or without sequential radiotherapy, and definitive chemo-radiotherapy without surgical intervention (3-5).Multiple phase II and III clinical trials proved the clinical practicality and improved survival of neoadjuvant chemotherapy (3,(5)(6)(7)(8)(9)(10)(11)(12). In many of these studies, the downstaging of the lymph nodes and complete surgical resection are predictors of long-term survival (6,7,13).The global 5-year survival of the N2 NSCLC patients is 20-25% but analysing the patients' subgroups, the 5-year survival is 42% for those responding to chemotherapy and 10%, respectively, for those without chemotherapeutic response ( 14).In our previous study (15), we performed microarray experiments on tumoral and non-tumoral tissue samples derived from tumoral and non-tumoral mediastinal lymph node surgically removed before neoadjuvant chemotherapy treatment from 27 patients with stage IIIA (N2) NSCLC. Based on the response to neoadjuvant chemotherapy, patients were divided in two groups: non-responders (group A), patients with progression or pathological confirmation of persistent mediastinal disease and responders (group B), patients with pathological confirmation of mediastinal down staging. A total of 1,127 genes were identified with modified expression in tumoral tissue compared to normal tissue at p≤0.05 and 44 genes at p≤0.01 (15). Genes with the highest difference in gene ...

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