Culture and multiomic analysis of lung cancer patient-derived pleural effusions revealed distinct druggable molecular types

Ha Young Seo, Soon Chan Kim, Woo lee Roh, Young Kyoung Shin, Soyeon Kim, Dong Wan Kim, Tae Min Kim, Ja Lok Ku

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Malignant pleural effusion (MPE) is an independent determinant of poor prognostic factor of non-small cell lung cancer (NSCLC). The course of anchorage independent growth within the pleural cavity likely reforms the innate molecular characteristics of malignant cells, which largely accounts for resistance to chemotherapy and poor prognosis after the surgical resection. Nevertheless, the genetic and transcriptomic features with respect to various drug responses of MPE-complicated NSCLC remain poorly understood. To obtain a clearer overview of the MPE-complicated NSCLC, we established 28 MPE-derived lung cancer cell lines which were subjected to genomic, transcriptomic and pharmacological analysis. Our results demonstrated MPE-derived NSCLC cell lines recapitulated representative driver mutations generally found in the primary NSCLC. It also exhibited the presence of distinct translational subtypes in accordance with the mutational profiles. The drug responses of several targeted chemotherapies accords with both genomic and transcriptomic characteristics of MPE-derived NSCLC cell lines. Our data also suggest that the impending drawback of mutation-based clinical diagnosis in evaluating MPE-complicated NSCLS patient responses. As a potential solution, our work showed the importance of comprehending transcriptomic characteristics in order to defy potential drug resistance caused by MPE.

Original languageEnglish
Article number6345
JournalScientific Reports
Volume12
Issue number1
DOIs
StatePublished - Dec 2022

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