Integrative network analysis of early-stage lung adenocarcinoma identifies aurora kinase inhibition as interceptor of invasion and progression

Seungyeul Yoo, Abhilasha Sinha, Dawei Yang, Nasser K. Altorki, Radhika Tandon, Wenhui Wang, Deebly Chavez, Eunjee Lee, Ayushi S. Patel, Takashi Sato, Ranran Kong, Bisen Ding, Eric E. Schadt, Hideo Watanabe, Pierre P. Massion, Alain C. Borczuk, Jun Zhu, Charles A. Powell

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Here we focus on the molecular characterization of clinically significant histological subtypes of early-stage lung adenocarcinoma (esLUAD), which is the most common histological subtype of lung cancer. Within lung adenocarcinoma, histology is heterogeneous and associated with tumor invasion and diverse clinical outcomes. We present a gene signature distinguishing invasive and non-invasive tumors among esLUAD. Using the gene signatures, we estimate an Invasiveness Score that is strongly associated with survival of esLUAD patients in multiple independent cohorts and with the invasiveness phenotype in lung cancer cell lines. Regulatory network analysis identifies aurora kinase as one of master regulators of the gene signature and the perturbation of aurora kinases in vitro and in a murine model of invasive lung adenocarcinoma reduces tumor invasion. Our study reveals aurora kinases as a therapeutic target for treatment of early-stage invasive lung adenocarcinoma.

Original languageEnglish
Article number1592
JournalNature Communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

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