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

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Cancer Biology & Medicine 2020年第2期17卷 444-457页

作者： Juan Moreno-Rubio Santiago Ponce Rosa Alvarez maria Eugenia Olmedo Sandra Falagan Xabier Mielgo Fatima Navarro Patricia Cruz Luis Cabezon-Gutierrez Carlos Aguado Gonzalo Colmenarejo Marta Munoz-Fernandez de Leglaria Ana Belen Enguita maria cebollero Amparo Benito Isabel Alemany Carolina del Castillo Ricardo Ramos Ana Ramirez de Molina Enrique Casado maria Sereno Ana Ramirez de Molina1 Enrique Casado5Maria Sereno5 XIMDEA Food InstituteCEI UAM+CSICMadrid 28702Spain 12 de Octubre University Hospital Madrid 28041Spain Gregorio Maranon University Hospital Madrid 28009Spain Ramon y Cajal University Hospital Madrid 28034Spain Infanta Sofia University Hospital San Sebastian De Los ReyesMadrid 28702Spain Fundacion Alcorcon University Hospital AlcorconMadrid 28922Spain Prlncipe de Asturias University Hospital Alcala De HenaresMadrid 28805Spain La Paz University Hospital Madrid 28046Spain University Hospital of Torrejon Torrejon De ArdozMadrid 28850Spain Clinico San Carlos University Hospital Madrid 28040Spain Parque Cientifico de Madrid Foundation Madrid 28049Spain

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(T FF1),serpin,Ca-channels,and Tolllike 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 SFT PC(P=0.047).Conclusions:We present a sequential genetic analysis of a sample of NSCLCLS with no driver alterations,obtaining a differential RNA-seq/RT-PCR profile showing an abnormal expression of SF genes.

关键词： Long-term survivors non-small cell lung cancer surfactant proteins

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