Differential Proteomic Analysis between Small Cell Lung Carcinoma (SCLC) and Pulmonary Carcinoid Tumors Reveals Molecular Signatures for Malignancy in Lung Cancer

• Published in: Proteomics. Clinical applications Vol. 12; no. 6; pp. e1800015 - n/a
• Main Authors: Fujii, Kiyonaga, Miyata, Yuka, Takahashi, Ikuya, Koizumi, Hirotaka, Saji, Hisashi, Hoshikawa, Masahiro, Takagi, Masayuki, Nishimura, Toshihide, Nakamura, Haruhiko
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.11.2018
• Subjects: Cancer; Cell cycle; Deoxyribonucleic acid; Design of experiments; DNA; DNA biosynthesis; Experimental design; Lung cancer; Lung carcinoma; Malignancy; Medical prognosis; Metabolism; Metastases; MSH2 protein; Network analysis; Neuroendocrine tumors; Paraffin; Paraffins; Prognosis; Proteins; proteomic analysis; Ribonucleic acid; RNA; RNA transport; SCLC; Signatures; Small cell lung carcinoma; Survival; Survival analysis; Therapeutic applications; Tissues; Tumor cells; Tumors; lung cancer; SCLC; malignancy; prognosis; proteomic analysis
• ISSN: 1862-8346; 1862-8354
• DOI: 10.1002/prca.201800015

Purpose The molecular underpinnings that may prognosticate survival and increase our understanding of tumor development and progression are still poorly understood. This study aimed to define the molecular signatures for malignancy in small cell lung carcinoma (SCLC), which is known for its highly aggressive clinical features and poor prognosis. Experimental design Using clinical specimens, the authors perform a comparative proteomic analysis of high‐grade SCLCs and low‐grade pulmonary carcinoid tumors (PCTs), both of which are types of neuroendocrine tumors. A label‐free LC‐MS‐based quantitative proteomic analysis is applied to tumor cells laser‐microdissected from their formalin‐fixed paraffin‐embedded (FFPE) tissues obtained from six patients each. Results Overall, 1991 proteins are identified from tumor cells in the FFPE tissues. Through the protein–protein interaction network analysis of 201 proteins significantly, the authors find that SCLC is functionally characterized by activation of molecular pathways for spliceosome, RNA transport, and DNA replication and cell cycle. Particularly, 11 proteins involved in tumor proliferation (MCM2, 4, 6, 7, and MSH2), metastasis (RCC2, CORO1C, CHD4, and IPO9), and cancer metabolism (PHGDH and TYMP) are identified as SCLC‐specific proteins. Furthermore, their prognostic significances are demonstrated by online Kaplan–Meier survival analysis. Conclusions and clinical relevance These clinical tissue proteomic approach for SCLC reveals the proteins associated with aggressiveness and poor prognosis. The identified SCLC‐specific proteins represent potential therapeutic targets. Moreover, MCMs and PHGDH can be poor prognostic factors for lung cancer.