Integrative Analysis for Identification of Therapeutic Targets and Prognostic Signatures in Non-Small Cell Lung Cancer

Abstract

Differential expressions of certain genes during tumorigenesis may serve to identify novel manageable targets in the clinic. In this work with an integrated bioinformatics approach, we analyzed public microarray datasets from Gene Expression Omnibus (GEO) to explore the key differentially expressed genes (DEGs) in non-small cell lung cancer (NSCLC). We identified a total of 984 common DEGs in 252 healthy and 254 NSCLC gene expression samples. The top 10 DEGs as a result of pathway enrichment and protein–protein interaction analysis were further investigated for their prognostic performances. Among these, we identified high expressions of CDC20, AURKA, CDK1, EZH2, and CDKN2A genes that were associated with significantly poorer overall survival in NSCLC patients. On the contrary, high mRNA expressions of CBL, FYN, LRKK2, and SOCS2 were associated with a significantly better prognosis. Furthermore, our drug target analysis for these hub genes suggests a potential use of Trichostatin A, Pracinostat, TGX-221, PHA-793887, AG-879, and IMD0354 antineoplastic agents to reverse the expression of these DEGs in NSCLC patients.

A Systematic Review of Progress toward Unlocking the Power of Epigenetics in NSCLC: Latest Updates and Perspectives

“…Prominent examples in this regard include histone deacetylase inhibitors (HDACs) and DNA methyltransferase inhibitors (DNMTs). It has been observed that HDAC inhibitors, such as vorinostat (SAHA) [ 140 ], panobinostat (LBH589) [ 141 ], belinostat (PXD-101) [ 142 ], and trichostatin A (TSA) [ 143 ], can reduce the expression of genes associated with tumor growth and metastasis. Additionally, DNMT inhibitors, such as decitabine and azacitidine, have revealed their potential by reversing gene promoter hypermethylation, a hallmark of cancer [ 144 ].…”

“…Trichostatin A (TSA) has been identified as a promising therapeutic option for NSCLC by multiple studies. Erkin et al determined that trichostatin A, pracinostat, TGX-221, PHA-793887, AG-879, and IMD0354 had the potential to reverse the expression of the differentially expressed genes (DEG) genes such as CDC20 , AURKA , CDK1 , EZH2 , and CDKN2A in NSCLC [ 143 ]. Sindo et al suggested that quisinostat (JNJ-2648158) and TSA can induce G1 arrest and inhibit migration of A549 cells, as well as improve mitochondrial respiration and elevate CLDN-7 expression.…”

EZH2 as a prognostic-related biomarker in lung adenocarcinoma correlating with cell cycle and immune infiltrates

“…Docetaxel, palbociclib, and angiogenesis-inhibitor were among the extensively used compounds for the treatment of tumor, as determined by their scores. Other drugs/molecules, such as MK-1775 [ 34 , 35 ], MK-5108 [ 36 ], fenbendazole [ 37 , 38 ], albendazole [ 39 ], BAY-K8644 [ 40 ], evodiamine [ 41 ], purvalanol-a [ 42 ], mycophenolic-acid [ 43 ], PHA-793887 [ 44 ], cyclopamine [ 45 ], is a possible treatment for lung adenocarcinoma (Tables 5 , 6 ). To determine the therapeutic potential of these drugs/molecules in patients with lung adenocarcinoma with high EZH2 expression, additional research is necessary.…”

“…Docetaxel, palbociclib, and angiogenesis-inhibitor were among the extensively used compounds for the treatment of tumor, as determined by their scores. We have identified some potential drugs or molecules for the treatment of lung adenocarcinoma by reading the literature, such as MK-1775 [ 34 , 35 ], MK-5108 [ 36 ], fenbendazole [ 37 , 38 ], albendazole [ 39 ], BAY-K8644 [ 40 ], evodiamine [ 41 ], purvalanol-a [ 42 ], mycophenolic-acid [ 43 ], PHA-793887 [ 44 ], and cyclopamine [ 45 ] (Tables 5 , 6 ). Of interest is the WEE1 inhibitor MK-1775, which has shown potential chemotherapy or radiotherapy sensitivity in preclinical models, particularly, although not exclusively, in p53 mutated or deficient cancer cells [ 52 ].…”