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<p>Cathepsin D (CTSD) is a lysosomal protease involved in various biological processes, including apoptosis and autophagy, which play crucial roles in cancer development and progression. However, the impact of missense SNPs in the CTSD gene on protein structure, function, and their potential as cancer biomarkers remains unexplored. Hence, this study aimed to perform an in-silico analysis to assess the structural and functional impact of missense SNPs in the human CTSD protein and identify potential novel cancer SNP biomarkers. Missense SNPs in the CTSD gene were analyzed using multiple bioinformatics tools, and the effects of SNPs on protein stability, structural disruption, evolutionary conservation, and energy minimization were also evaluated. Clinical significance and cancer-specific mutations were assessed using canSar.ai and cBioPortal databases. In addition, protein-protein interaction (PPI) networks and pathway analyses were conducted to understand the functional implications of the identified SNPs. Out of 178 identified unique missense SNPs, 32 (18%) were predicted to be highly deleterious, damaging, and disease-causing, and 12 SNPs were predicted to disrupt protein structure and present at highly conserved positions. Energy minimization analysis revealed significant destabilization of the CTSD structure by specific SNPs. Notably, the W383C and G149R mutations were identified as potential novel SNP biomarkers for lung cancer and colorectal cancer, respectively. PPIs and pathway enrichment analyses highlighted the importance of CTSD in apoptosis, autophagy, and lysosomal pathways, suggesting that disruption of these pathways by CTSD SNPs may contribute to cancer development. Therefore, the discovery of deleterious CTSD mutations as potential biomarkers for lung and colorectal cancers could open up new avenues for targeted screening and personalized treatment approaches by restoring the delicate balance of apoptosis and autophagy. Therefore, this study provides a valuable foundation for future clinical studies and the translation of these findings into practical applications for improved patient outcomes.</p>

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In-silico analysis of structural and functional impact of missense SNPs of human CTSD protein on cancers and identification of potential novel cancer SNP biomarkers

  • 期刊论文

  • 发表日期：

    2025年11月20日

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  • Azrin Ahmed,
  • K.M. Tanjida Islam,
  • Saborni Sarker,
  • Shahin Mahmud

摘要

Cathepsin D (CTSD) is a lysosomal protease involved in various biological processes, including apoptosis and autophagy, which play crucial roles in cancer development and progression. However, the impact of missense SNPs in the CTSD gene on protein structure, function, and their potential as cancer biomarkers remains unexplored. Hence, this study aimed to perform an in-silico analysis to assess the structural and functional impact of missense SNPs in the human CTSD protein and identify potential novel cancer SNP biomarkers. Missense SNPs in the CTSD gene were analyzed using multiple bioinformatics tools, and the effects of SNPs on protein stability, structural disruption, evolutionary conservation, and energy minimization were also evaluated. Clinical significance and cancer-specific mutations were assessed using canSar.ai and cBioPortal databases. In addition, protein-protein interaction (PPI) networks and pathway analyses were conducted to understand the functional implications of the identified SNPs. Out of 178 identified unique missense SNPs, 32 (18%) were predicted to be highly deleterious, damaging, and disease-causing, and 12 SNPs were predicted to disrupt protein structure and present at highly conserved positions. Energy minimization analysis revealed significant destabilization of the CTSD structure by specific SNPs. Notably, the W383C and G149R mutations were identified as potential novel SNP biomarkers for lung cancer and colorectal cancer, respectively. PPIs and pathway enrichment analyses highlighted the importance of CTSD in apoptosis, autophagy, and lysosomal pathways, suggesting that disruption of these pathways by CTSD SNPs may contribute to cancer development. Therefore, the discovery of deleterious CTSD mutations as potential biomarkers for lung and colorectal cancers could open up new avenues for targeted screening and personalized treatment approaches by restoring the delicate balance of apoptosis and autophagy. Therefore, this study provides a valuable foundation for future clinical studies and the translation of these findings into practical applications for improved patient outcomes.