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 () and Charles A. Powell ()
Additional contact information
Seungyeul Yoo: Icahn School of Medicine at Mount Sinai
Abhilasha Sinha: Icahn School of Medicine at Mount Sinai
Dawei Yang: Icahn School of Medicine at Mount Sinai
Nasser K. Altorki: Weill Cornell Medicine-New York Presbyterian Hospital
Radhika Tandon: St. George’s University
Wenhui Wang: Icahn School of Medicine at Mount Sinai
Deebly Chavez: Icahn School of Medicine at Mount Sinai
Eunjee Lee: Icahn School of Medicine at Mount Sinai
Ayushi S. Patel: Icahn School of Medicine at Mount Sinai
Takashi Sato: Icahn School of Medicine at Mount Sinai
Ranran Kong: Icahn School of Medicine at Mount Sinai
Bisen Ding: Icahn School of Medicine at Mount Sinai
Eric E. Schadt: Icahn School of Medicine at Mount Sinai
Hideo Watanabe: Icahn School of Medicine at Mount Sinai
Pierre P. Massion: Vanderbilt University Medical Center
Alain C. Borczuk: Weill Cornell Medicine
Jun Zhu: Icahn School of Medicine at Mount Sinai
Charles A. Powell: Icahn School of Medicine at Mount Sinai

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-29230-7

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