Transcriptomics-based analysis of potential pathogenic mechanisms in presenile cataract

Objective  To investigate differentially expressed genes (DEGs) associated with presenile cataract and to explore their potential pathogenic mechanisms using transcriptomic analysis.

Methods  A case-control study was conducted. A total of 96 patients (96 eyes) with cataract who underwent surgery at the First Affiliated Hospital of Zhengzhou University from September 2023 to September 2024 were enrolled, including 48 patients (48 eyes) with presenile cataract and 48 patients (48 eyes) with age-related cataract. General clinical data were collected from both groups. After matching, anterior lens capsule samples were obtained for messenger RNA sequencing. Gene Ontology and Kyoto Encyclopedia of Genes (KEGG) and Genomes analyses were performed to identify functional enrichment of DEGs, and a competing endogenous RNA interaction network was constructed. Key genes with significant differential expression were further validated by quantitative real-time PCR. This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (No. 2022-KY-0006-001). Written informed consent was obtained from all participants.

Results  A total of 678 DEGs were identified, including 33 upregulated and 645 downregulated genes. Gene Ontology analysis yielded 679 enriched terms, predominantly related to cellular components, protein binding, and biological development. KEGG pathway analysis indicated significant enrichment in cancer-related pathways, the mTOR signaling pathway, and the HIF-1 signaling pathway. A lncRNA-miRNA-mRNA competing endogenous RNA network was constructed with ACTN4, COX7A1, SCG5, and SERPINE1 as target genes and 36 interacting miRNAs and 48 interacting lncRNAs were identified. Quantitative real-time PCR results demonstrated that the expression levels of COX7A1, SCG5, and SERPINE1 of anterior lens capsule tissues in the presenile cataract group were 19.090±7.975, 5.871±1.911, and 7.996±2.190, respectively, which were all significantly higher than 1.014±0.213, 1.060±0.408, and 1.013±0.194 in the age-related cataract group ( t=3.925, 4.266, 5.501; all P<0.05); ACTN4 expression in the presenile cataract group was (0.403±0.200), which was significantly lower than 1.022±0.268 in the age-related cataract group ( t=3.213, P<0.05), and the expression results were consistent with the sequencing data.

Conclusions   ACTN4, COX7A1, SCG5, and SERPINE1 are aberrantly expressed in the anterior lens capsule of patients with presenile cataract and may participate in its pathogenesis by affecting organelle function, protein interactions, and signaling pathways such as mTOR and HIF-1.