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

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.

Integrated Transcriptome Profiling Identifies Prognostic Hub Genes as Therapeutic Targets of Glioblastoma: Evidenced by Bioinformatics Analysis

“…GEPIA2 is a web-based server that analyzes the expression of tumors and normal samples from the Cancer Genome Atlas (TCGA). GSE4290 consists of 76 LGG samples (includes 26 astrocytomas and 50 oligodendrogliomas), 81 GBM samples, and 23 nontumor samples . GSE15824 contains 30 brain tumor samples (12 primary glioblastomas (GBM), 3 secondary glioblastomas (GBM-2), 8 astrocytomas (Astro) and 7 oligodendrogliomas (Oligo)) and 5 normal brain tissues .…”

“…The expression levels of hub genes were validated using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2 131 ) server and two microarray data sets, i.e., GSE15824 and GSE4290. 132 GEPIA2 is a web-based server that analyzes the expression of tumors and normal samples from the Cancer Genome Atlas (TCGA). GSE4290 consists of 76 LGG samples (includes 26 astrocytomas and 50 oligodendrogliomas), 81 GBM samples, and 23 nontumor samples.…”

“…GSE4290 consists of 76 LGG samples (includes 26 astrocytomas and 50 oligodendrogliomas), 81 GBM samples, and 23 nontumor samples. 132 GSE15824 contains 30 brain tumor samples (12 primary glioblastomas (GBM), 3 secondary glioblastomas (GBM-2), 8 astrocytomas (Astro) and 7 oligodendrogliomas (Oligo)) and 5 normal brain tissues. 99 Thus, the expression and correlation of the hub genes can be validated in GBM tissues and normal tissues.…”

The ubiquitin-ligase TRAF6 and TGFβ type I receptor form a complex with Aurora kinase B contributing to mitotic progression and cytokinesis in cancer cells

“…Aurora kinase A (AURKA) and B (AURKB) are overexpressed in many tumors, including breast, lung, pancreatic, ovarian, and prostate tumors. 30 , 31 , 32 AURKB is a component of the chromosomal passenger complex (CPC), which also contains the inner centromere protein (INCENP), survivin, and borealin. 33 , 34 AURKB binds to the conserved C-terminal IN-box region of INCENP, 35 where a Thr-Ser-Ser (TSS) motif is located, which is phosphorylated by AURKB, 36 contributing to AURKB activation and stabilization of the complex.…”

Cuproptosis-related gene signatures for predicting prognosis of lung adenocarcinoma

“…[ 1 ] LC is an extremely heterogeneous disease, and tumors with similar histology may have different outcomes. [ 2 ] Despite the tremendous progress in the development of new therapies for oncology, the prognosis is poor. Currently, several drugs are commercially available that exert anticancer effects by inducing apoptosis.…”