Abstract 3158: Checkpoint Kinase I, Cyclin E1, and Exonuclease I genes play role in the survival of lung adenocarcinoma patients

Abstract According to the SEER program of NCI, lung, and bronchus cancer are the second most common cancer with an estimated 236,740 diagnoses in 2022. Fifty-four percent of the patients are expected to die of the disease in the United States alone. The five-year overall survival rate for these cancers is 22.9 percent. Lung adenocarcinoma (LUAD) accounts for forty percent of all lung cancer cases in the United States. Genetic biomarker-based early detection and precision treatment of LUAD patients can play a critical role in the reduction of the mortality rate. The purpose of this investigation was to use an integrated bioinformatics approach to identify differentially expressed Hub genes in LUAD with > 10 connections in the genetic interaction network(s). The higher number of genetic interactions potentially suggests their important role in patient survival. Out of 23,483 genes from seven published cancer studies and databases, we identified 107 significantly altered (up or down-regulated) genes that are common to all data sources. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) showed that many of the identified 107 genes were involved in DNA replication, DNA repair, ATP binding, and cancer pathways. A protein-protein interaction network was mapped with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). This analysis revealed 1116 protein-to-protein interactions (PPI) among the 107 genes. We selected 25 genes, which exhibited >30 PPI interactions each which showed Cox coefficients for gene expression, where a positive coefficient corresponds to a worse survival rate with higher levels of gene expression, while a negative coefficient corresponds to a better prognosis with lower levels of gene expression; it also provided a False Discovery Rate (FDR) with a corrected p-value. The Kaplan-Meier survival curves for genes that had an FDR of below 0.05 were graphed inside of the OncoLnc tool. Patients were subclassified into the low- and high-Hub gene expression level groups if the median expression was in the bottom 25 percentile or top 25 percentile. Hub genes isolated from Cytoscape were entered into OncoLnc to collect data on the relationship between LUAD patients (n=492) survival and gene expression, which resulted in the identification of three genes, Checkpoint Kinase 1, Cyclin E1, and Exonuclease 1. All three genes showed a significant correlation between increased differential expression in LUAD and worsened patient survival. These signature Hub genes (Checkpoint Kinase 1, Cyclin E1, and Exonuclease 1) and associated genetic networks can potentially be developed as early diagnostic markers or targets in precision gene therapies for improved prognosis of LUAD patients. Citation Format: Prateek Gupta, Leya Joykutty, Diaaidden Alwadi, Ana Ruas, Deodutta Roy, Quentin Felty, Alok Deoraj. Checkpoint Kinase I, Cyclin E1, and Exonuclease I genes play role in the survival of lung adenocarcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3158.