Integrated single-cell and transcriptome sequencing analyses determines a chromatin regulator-based signature for evaluating prognosis in lung adenocarcinoma

Abstract

BackgroundAccumulating evidence has highlighted the significance of chromatin regulator (CR) in pathogenesis and progression of cancer. However, the prognostic role of CRs in LUAD remains obscure. We aim to detect the prognostic value of CRs in LUAD and create favorable signature for assessing prognosis and clinical value of LUAD patients.MethodsThe mRNA sequencing data and clinical information were obtained from TCGA and GEO databases. Gene consensus clustering analysis was utilized to determine the molecular subtype of LUAD. Cox regression methods were employed to set up the CRs-based signature (CRBS) for evaluating survival rate in LUAD. Biological function and signaling pathways were identified by KEGG and GSEA analyses. In addition, we calculated the infiltration level of immunocyte by CIBERSORT algorithm. The expressions of model hub genes were detected in LUAD cell lines by real-time polymerase chain reaction (PCR).ResultsKEGG analysis suggested the CRs were mainly involved in histone modification, nuclear division and DNA modification. Consensus clustering analysis identified a novel CRs-associated subtype which divided the combined LUAD cohort into two clusters (C1 = 217 and C2 = 296). We noticed that a remarkable discrepancy in survival rate among two clusters. Then, a total of 120 differentially expressed CRs were enrolled into stepwise Cox analyses. Four hub CRs (CBX7, HMGA2, NPAS2 and PRC1) were selected to create a risk signature which could accurately forecast patient outcomes and differentiate patient risk. GSEA unearthed that mTORC1 pathway, PI3K/Akt/mTOR and p53 pathway were greatly enriched in CRBS-high cohort. Moreover, the infiltration percentages of macrophage M0, macrophage M2, resting NK cells, memory B cells, dendritic cells and mast cells were statistically significantly different in the two groups. PCR assay confirmed the differential expression of four model biomarkers.ConclusionsAltogether, our project developed a robust risk signature based on CRs and offered novel insights into individualized treatment for LUAD cases.

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

“…Our results provided new perspectives for LUAD prognosis management. A recent study also explored the function of CR in LUAD [ 25 ]. But there were still some obviously different between our study and previous.…”

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 ).…”

Unraveling the tumor immune microenvironment of lung adenocarcinoma using single-cell RNA sequencing

“…The prognostic markers and the indications for prognosis in these studies are summarized in Table 2 . 36 , 44 , 45 , 47 – 49 , 55 – 89 DEGs and their combined prognostic model were the most common types of prognostic markers in these studies. For example, one study identified nine cancer-specific DEGs (CBFA2T3, CR2, SEL1L3, TM6SF1, TSPAN32, ITGA6, MAPK11, RASA3, and TLR6) and established a prognostic risk model in combination with clinical factors.…”