Identifying transcript variants associated with colon cancer: a comparative analysis of 3D spheroid cultures and patient-derived tissues

Introduction Colon cancer remains one of the leading causes of cancer-related deaths worldwide, necessitating a deeper understanding of the molecular factors contributing to its development. By exploring the transcriptomic landscape of colon cancer cell lines and patient-derived tissues, this study aspires to uncover novel biomarkers and potential therapeutic targets for improving colon cancer diagnosis and treatment. Material and method The SW620, HCT116 and DLD-1 colon cancer cell lines and immortalized cells derived from healthy gut mucosa HCEC-1CT were cultivated in 3D as spheroids and analyzed by RNA sequencing using Illumina's NovaSeq 6000 platform. Our transcriptomic data were compared with the results of previously published comprehensive transcriptomic study based on 473 patient-derived tumor and 417 non-tumor tissues. Result and discussion Comparison of the transcriptomic results obtained for cell lines grown as spheroids with the results of the RNA sequencing data for patient-derived tissues was conducted for 375 transcripts identified by the previously published study as significantly differentially expressed in colon cancer (39 overexpressed and 336 underexpressed). Among these, 32 transcripts were identified with expression patterns in colon cell lines corresponding to the expression patterns observed in patient-derived tissues (4 overexpressed and 28 under expressed). Most prominently deregulated transcripts among those with corresponding deregulated expression patterns in colon cell lines and patient-derived tumors were NTMT1-204 (overexpressed in cancer) and DCTN1-205 (underexpressed in cancer). For other 343 transcripts, matching deregulation pattern observed in patient-derived tissues was not confirmed in colon cell lines and their expression patterns in stromal cell types should be further investigated. Conclusion Overall, comparison of RNA sequencing data between colon cell lines grown as spheroids and patient-derived tissues revealed a set of 32 transcripts that may be relevant for colon carcinogenesis and their role in gut epithelial cells should be further explored. Additionally, NTMT1-204 transcript could potentially be used as diagnostic marker for colon cancer, and DCTN1-205 as a potential therapeutical agent.