Comprehensive analyses reveal the prognosis and biological function roles of chromatin regulators in lung adenocarcinoma

Abstract

The present study explored the prognosis and biological function roles of chromatin regulators (CRs) in patients with lung adenocarcinoma (LUAD). Using transcriptome profile and clinical follow-up data of LUAD dataset, we explored the molecular classification, developed, and validated a CR prognostic model, built an individual risk scoring system in LUAD, and compared the clinical and molecular characteristics between different subtypes and risk stratifications. We investigated the chemotherapy sensitivity and predicted potential immunotherapy response. Lastly, we collected the clinical samples and validated the prognosis and potential function role of NAPS2. Our study indicated that LUAD patients could be classified into two subtypes that had obviously different clinical background and molecular features. We constructed a prognostic model with eight CR genes, which was well validated in several other population cohort. We built high- and low-risk stratifications for LUAD patients. Patients from high-risk group were totally different from low-risk groups in clinical, biological function, gene mutation, microenvironment, and immune infiltration levels. We idented several potential molecular compounds for high-risk group treatment. We predicted that high-risk group may have poor immunotherapy response. We finally found that Neuronal PAS Domain Protein 2 (NPAS2) involved in the progression of LUAD via regulating cell adhesion. Our study indicated that CR involved in the progression of LUAD and affect their prognosis. Different therapeutic strategies should be developed for different molecular subtypes and risk stratifications. Our comprehensive analyses uncover specific determinants of CRs in LUAD and provides implications for investigating disease-associated CRs.

A robust six-gene prognostic signature based on two prognostic subtypes constructed by chromatin regulators is correlated with immunological features and therapeutic response in lung adenocarcinoma

“…BUB1 was found as a prognostic factor for hepatocellular carcinoma [ 52 ]. In addition, some new prognostic CRs have also been identified in LUAD, such as NPAS2 and HMGA2 [ 53 , 54 ]. In this study, an interesting finding is that CIT was highly expressed as a protective gene in LUAD tissue, and the high expression of CIT was significantly associated with a high OS rate ( Figure 14B ).…”