Integrative network analysis of early-stage lung adenocarcinoma identifies aurora kinase inhibition as interceptor of invasion and progression.
Seungyeul YooAbhilasha SinhaDawei YangNasser K AltorkiRadhika TandonWenhui WangDeebly ChavezEunjee LeeAyushi S PatelTakashi SatoRanran KongBisen DingEric E SchadtHideo WatanabePierre P MassionAlain C BorczukJun ZhuCharles A PowellPublished in: Nature communications (2022)
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.
Keyphrases
- network analysis
- early stage
- genome wide
- cell migration
- copy number
- end stage renal disease
- genome wide identification
- transcription factor
- sentinel lymph node
- newly diagnosed
- chronic kidney disease
- peritoneal dialysis
- squamous cell carcinoma
- prognostic factors
- radiation therapy
- combination therapy
- neoadjuvant chemotherapy
- locally advanced
- replacement therapy
- patient reported