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

Juan Moreno-Rubio, Santiago Ponce, Rosa Álvarez, et al.

Abstract


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 prognosisfactors for these cases [stage, Eastern Cooperative Oncology Group (ECOG), etc .], but more data are required in the literature. In thismulti-center study, we focused on LS of advanced NSCLC with OS above 36 months to perform a clinical-pathological and molecularcharacterization.

Methods: In the first step, we conducted a clinical-pathological characterization of the patients. Afterwards, we carried out a geneticanalysis by comparing LS to a sample of short-term survivors (SS) (with an OS less than 9 months). We initially used whole-genomeRNA-seq to identify differentiating profiles of LS and SS, and later confirmed these with reverse transcription-polymerase chainreaction (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 NSCLCwith an ECOG of 0–1. We obtained an initial differential transcriptome expression, displaying 5 over- and 33 under-expressed genesinvolved in different pathways: namely, the secretin receptor, surfactant protein, trefoil factor 1 (TFF1), serpin, Ca-channels, and Tolllikereceptor (TLRs) families. Finally, RT-PCR analysis of 40 (20 LS/20 SS) samples confirmed that four genes (surfactant proteinsand 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 differentialRNA-seq/RT-PCR profile showing an abnormal expression of SF genes.

Cite this article as: Moreno-Rubio J, Ponce S, Álvarez R, Olmedo ME, Falagan S,Mielgo X, et al. Clinical-pathological and molecular characterization oflong-term survivors with advanced non-small cell lung cancer. Cancer BiolMed. 2020; 17: 444-457. doi: 10.20892/j.issn.2095-3941.2019.0363


Keywords


Long-term survivors; non-small cell lung cancer; surfactant proteins

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