Clinical-pathological and molecular characterization of long-term survivors with advanced non-small cell lung cancer

Autor: Fatima Navarro, Sandra Falagan, Luis Cabezon-Gutierrez, X. Mielgo, Carolina Castillo, Carlos Aguado, Enrique Casado, Gonzalo Colmenarejo, Ana Ramírez de Molina, M. Cebollero, Juan Moreno-Rubio, Ana Belén Enguita, María Sereno, Ricardo Luiz Ramos, Isabel Alemany, Patricia Cruz, Santiago Ponce, Rosa Alvarez, Maria Eugenia Olmedo, Amparo Benito, Marta Muñoz-Fernández de Leglaria
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Oncology
Cancer Research
medicine.medical_specialty
Lung Neoplasms
Pulmonary Surfactant-Associated Proteins
medicine.medical_treatment
Genetic analysis
lcsh:RC254-282
Transcriptome
03 medical and health sciences
0302 clinical medicine
Cancer Survivors
SFTPA2
Carcinoma
Non-Small-Cell Lung

Internal medicine
medicine
Humans
RNA-Seq
Protein Precursors
Stage (cooking)
Receptor
Lung cancer
non-small cell lung cancer
Aged
Neoplasm Staging
Retrospective Studies
Chemotherapy
Pulmonary Surfactant-Associated Protein A
Reverse Transcriptase Polymerase Chain Reaction
business.industry
Middle Aged
medicine.disease
surfactant proteins
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Pulmonary Surfactant-Associated Protein C
Survival Analysis
030228 respiratory system
Spain
030220 oncology & carcinogenesis
long-term survivors
Adenocarcinoma
Original Article
Female
business
Zdroj: Cancer Biology & Medicine, Vol 17, Iss 2, Pp 444-457 (2020)
Cancer Biology & Medicine
ISSN: 2095-3941
Popis: Objective: Long-term survivors (LS) of non-small cell lung cancer (NSCLC) without driver alterations, displaying an overall survival (OS) of more than 3 years, comprise around 10% of cases in several series treated with chemotherapy. There are classical prognosis factors for these cases [stage, Eastern Cooperative Oncology Group (ECOG), etc.], but more data are required in the literature. In this multi-center study, we focused on LS of advanced NSCLC with OS above 36 months to perform a clinical-pathological and molecular characterization. Methods: In the first step, we conducted a clinical-pathological characterization of the patients. Afterwards, we carried out a genetic analysis by comparing LS to a sample of short-term survivors (SS) (with an OS less than 9 months). We initially used whole-genome RNA-seq to identify differentiating profiles of LS and SS, and later confirmed these with reverse transcription-polymerase chain reaction (RT-PCR) for the rest of the samples. Results: A total of 94 patients were included, who were mainly men, former smokers, having adenocarcinoma (AC)-type NSCLC with an ECOG of 0–1. We obtained an initial differential transcriptome expression, displaying 5 over- and 33 under-expressed genes involved in different pathways: namely, the secretin receptor, surfactant protein, trefoil factor 1 (TFF1), serpin, Ca-channels, and Toll-like receptor (TLRs) families. Finally, RT-PCR analysis of 40 (20 LS/20 SS) samples confirmed that four genes (surfactant proteins and SFTP) were significantly down-regulated in SS compared to LS by using an analysis of covariance (ANCOVA) model: SFTPA1 (P = 0.023), SFTPA2 (P = 0.027), SFTPB (P = 0.02), and SFTPC (P = 0.047). Conclusions: We present a sequential genetic analysis of a sample of NSCLC LS with no driver alterations, obtaining a differential RNA-seq/RT-PCR profile showing an abnormal expression of SF genes.
Databáze: OpenAIRE