Identification of EARS2 as a Potential Biomarker with Diagnostic, Prognostic, and Therapeutic Implications in Colorectal Cancer

Abstract

Ling Wang,1,2,* Xuemei Deng,1,* Jiaxi Tang,3 Yi Gong,2 Shaojin Bu,4 Zuli Li,1 Bin Liao,2 Yao Ding,2 Tingting Dai,1,5 Yong Liao,1 Yongsheng Li2,6 1Department of Infectious Diseases, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Phase I Clinical Trial Ward, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, People’s Republic of China; 3Department of Anesthesiology, Chongqing University Cancer Hospital, Chongqing, China; 4Department of Anesthesiology, Fengdu People’s Hospital, Chongqing, People’s Republic of China; 5Department of Medical Oncology, Chongqing University Fuling Hospital, Chongqing, China; 6Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong Liao, Department of Infectious Diseases, Second Affiliated Hospital, Chongqing Medical University, NO. 288 Chayuan Astronomy Avenue, Nanan District, Chongqing, 401336, People’s Republic of China, Email [email protected] Yongsheng Li, Department of Medical Oncology, Chongqing University Cancer Hospital, No. 181 hanyu Road, Shapingba District, Chongqing, 400030, People’s Republic of China, Email [email protected]: Colorectal cancer (CRC) is a prevalent malignancy, and lactate metabolism significantly influences tumorigenesis and progression. This study identifies key genes associated with lactic acid metabolism and explore their impact on CRC.Patients and Methods: This study utilized data from The Cancer Genome Atlas, Gene Expression Omnibus, other public databases, and our institutional resources. Machine learning identified key lactate metabolism-related genes. Receiver Operating Characteristic analysis, Kaplan-Meier analysis, and the construction of a nomogram model were conducted to assess the diagnostic and prognostic significance of the key lactate metabolism-related gene EARS2. EARS2 expression in colorectal tissue was validated using both publicly available external data and samples from our institution. To investigate the mechanisms underlying EARS2 in CRC, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment Analysis, and Protein-Protein Interaction analyses were performed, alongside the construction of miRNA-mRNA interaction networks. Additionally, the relationships between EARS2 and immune cell infiltration, as well as responses to drug therapy, were examined. Following the knockdown of EARS2, we assessed cell proliferation, migration capabilities, and apoptosis. Statistical analyses were conducted using R and GraphPad Prism software.Results: ERAS2 was overexpressed in CRC tissues compared to normal and adenoma tissues, with higher expression levels correlating with aberrant lactate metabolism and poorer patient prognosis. EARS2 was involved in pathways such as neuroactive ligand-receptor interactions, protein digestion, and cholesterol metabolism, and it was associated with immune cell infiltration and responses to drug treatment. Additionally, the knockdown of EARS2 inhibited the proliferation, migration, and invasion of CRC cells while enhancing their apoptosis.Conclusion: Elevated expression of EARS2 is associated with abnormal lactate metabolism, immune cell infiltration, altered therapeutic sensitivity, and poorer survival outcomes in CRC. This correlation suggests that EARS2 may serve as a potential target for the diagnosis, prognosis, and therapeutic intervention in 0CRC. Keywords: biomarker, CRC, EARS2, lactic acid, prediction model

Keywords

• biomarker
• crc
• ears2
• lactic acid
• prediction model