CLCA1 (Chloride Channel Accessory 1)

Our findings suggest that bile acid metabolism could shape the TIME via key genes CLCA1, UGT2A3, and ZG16, and subsequently modify CRC prognosis and immunotherapy responses. These genes may serve as potential prognostic indicators and mechanistic mediators linking bile acid metabolism to T-cell dysfunction, offering insights for future combination strategies targeting the metabolism-barrier-immunity axis.

Furthermore, enzyme-linked immunosorbent assay (ELISA) quantification of these glycoproteins in the serum of UC and CD patients showed increased expression of FGB and reduced expression of CLCA1 in both conditions, while FBN1 levels remained unchanged. These results collectively suggest that the quantitative analysis of site-specific glycosylation profiles could be crucial for differentiating UC from CD, thereby facilitating earlier and more accurate diagnosis.

Two pathomics-based machine learning models were developed to predict CLCA1 expression from H&E stained images of COAD. A theoretical basis for interpreting the disease model was developed by comprehensively analyzing the pathomics-based models and transcriptomic data, facilitating further hypothesis-driven experimental research.

CLCA1 and ZG16, which are lowly expressed in CRC tissues, are associated with poor prognosis of CRC and may be one of the markers for diagnostic screening and prediction of prognostic outcome in CRC. Meanwhile, CLCA1 and ZG16 may also be new targets for tumor immunotherapy.

Immunohistochemical validation was performed in tissue samples from patients with rectal and colon cancer. TMEM59L, CLCA1, and TUBB2B were independent prognostic factors associated with lymphatic metastasis of CRC.