RBPMS as a novel marker for cancer-associated fibroblasts in distinguishing left and right colorectal cancer sidedness
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Background
Colorectal cancer (CRC) can be classified into left-sided (LCRC) and right-sided CRC (RCRC). These CRC entities present different molecular phenotypes and prognosis. Accumulation of cancer-associated fibroblasts (CAFs) reflects poor prognosis and recurrence of CRC. CAF-cancer cell crosstalk regulates fibroblast activation and drives CRC progression, facilitated via secretomes including TGFβ1. CAF-cancer cell interplay according to colon sidedness have yet to be fully investigated due to the lack of robust marker for CAF.
Objective
To explore a novel CAF marker in differentiating the mechanisms of LCRC and RCRC.
Methods
CAFs from cancerous tissues of LCRC and RCRC patients and normal fibroblasts from adjacent normal colon tissues were established. Profiling of these fibroblasts were performed. Gene expression of the fibroblasts was analyzed via Affymetrix Clariom S (Human) assay, validated using Western blot. The effect of TGFβ1 on protein expression of fibroblasts was also studied. Epithelial cancer cell lines were used as controls.
Results
Fibroblast profiling showed differences in morphology and proliferation between CAFs and NFs, and pro-proliferative effect of CAFs on CRC cells. Molecular analyses revealed RNA-binding protein with multiple splicing ( RBPMS ) to be differentially expressed between CAFs and NFs from left and right colon. RBPMS was significantly upregulated in CAFs from LCRC compared to their respective NFs. In contrast, RBPMS was downregulated in CAFs from RCRC compared to their NFs ( p <0.05). Furthermore, TGFβ1 induced RBPMS expression in CAFs and NFs from the left colon, whereas it suppressed RBPMS expression in fibroblasts from right colon. CAFs from LCRC resembled myCAFs with myofibroblast-related expression signatures, whereas those from RCRC signified iCAFs with inflammatory marker expression.
Conclusion
This study highlighted RBPMS as a novel CAF marker in differentiating the mechanisms between LCRC and RCRC. This finding may be utilized in CAF-targeted therapy for CRC.
