Sachin Kumar1, Surender K Sharawat2, Ashraf Ali3, Vikas Gaur2, Prabhat Singh Malik2, Sunil Kumar4, Anant Mohan3, Randeep Guleria3. 1. Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India. Electronic address: sksingla@aiims.ac.in. 2. Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India. 3. Department of Pulmonary Critical Care and Sleep Medicine, All India Institute of Medical Sciences, New Delhi, India. 4. Department of Surgical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.
Abstract
PURPOSE: Identification of noninvasive blood-based biomarkers is of utmost importance for the early diagnosis and predicting prognosis of advance stage lung cancer patients. MicroRNAs (miRNAs) has been implicated in numerous diseases, however, their role as diagnostic and prognostic biomarkers in Indian lung cancer patients has not been evaluated yet. METHODS: For the identification of differentially expressed miRNAs in the serum of non-small cell lung cancer (NSCLC) patients, we performed small RNA sequencing. We validated the expression of 10 miRNAs in 75 NSCLC patients and 40 controls using quantitative reverse transcription polymerase chain reaction (PCR). miRNA expression was correlated with survival and therapeutic response. RESULTS: We identified 16 differentially expressed miRNAs in the serum of NSCLC patients as compared to controls. We observed significant downregulation of miR-15a-5p, miR-320a, miR-25-3p, miR-192-5p, let-7d-5p, let-7e-5p, miR-148a-3p, and miR-92a-3p in the serum of NSCLC patients. The expression of miR-375 and miR-10b-5p was significantly downregulated in lung squamous cell carcinoma patients than controls. The expression of miR-320a, miR-25-3p, and miR-148a-3p significantly correlated with stage. None of the miRNAs were correlated with survival outcome and therapeutic response. CONCLUSIONS: We conclude that the relative abundance of miRNAs in serum may be explored for the development of miRNA-based assays for better diagnosis and prognosis of NSCLC. Moreover, further studies are warranted to elucidate the role of some of the less explored miRNAs, such as miR-375 and miR-320a, in the pathogenesis of NSCLC.
PURPOSE: Identification of noninvasive blood-based biomarkers is of utmost importance for the early diagnosis and predicting prognosis of advance stage lung cancerpatients. MicroRNAs (miRNAs) has been implicated in numerous diseases, however, their role as diagnostic and prognostic biomarkers in Indian lung cancerpatients has not been evaluated yet. METHODS: For the identification of differentially expressed miRNAs in the serum of non-small cell lung cancer (NSCLC) patients, we performed small RNA sequencing. We validated the expression of 10 miRNAs in 75 NSCLCpatients and 40 controls using quantitative reverse transcription polymerase chain reaction (PCR). miRNA expression was correlated with survival and therapeutic response. RESULTS: We identified 16 differentially expressed miRNAs in the serum of NSCLCpatients as compared to controls. We observed significant downregulation of miR-15a-5p, miR-320a, miR-25-3p, miR-192-5p, let-7d-5p, let-7e-5p, miR-148a-3p, and miR-92a-3p in the serum of NSCLCpatients. The expression of miR-375 and miR-10b-5p was significantly downregulated in lung squamous cell carcinomapatients than controls. The expression of miR-320a, miR-25-3p, and miR-148a-3p significantly correlated with stage. None of the miRNAs were correlated with survival outcome and therapeutic response. CONCLUSIONS: We conclude that the relative abundance of miRNAs in serum may be explored for the development of miRNA-based assays for better diagnosis and prognosis of NSCLC. Moreover, further studies are warranted to elucidate the role of some of the less explored miRNAs, such as miR-375 and miR-320a, in the pathogenesis of NSCLC.
Authors: Florian Janke; Farastuk Bozorgmehr; Sabine Wrenger; Steffen Dietz; Claus P Heussel; Gudula Heussel; Carlos F Silva; Stephan Rheinheimer; Manuel Feisst; Michael Thomas; Heiko Golpon; Andreas Günther; Holger Sültmann; Thomas Muley; Sabina Janciauskiene; Michael Meister; Marc A Schneider Journal: Cancers (Basel) Date: 2020-04-12 Impact factor: 6.639