Single‐cell RNA sequencing reveals the heterogeneity of MYH11+ tumour‐associated fibroblasts between left‐sided and right‐sided colorectal cancer

Colorectal cancer (CRC) exhibits considerable heterogeneity on tumour location. However, there is still a lack of comprehensive annotation regarding the characteristics and differences between the left‐sided (L‐CRC) and right‐sided (R‐CRC) CRC. Here, we performed single‐cell RNA sequencing (scRNA‐seq) on immune and stromal cells from 12 L‐CRC and 10 R‐CRC patients. We found that L‐CRC exhibited stronger tumour invasion and poor prognosis compared with R‐CRC. In addition, functional enrichment analysis of a normal cohort showed that fibroblasts of left colon are associated with tumour‐related pathways. This suggested that the heterogeneity observed in both L‐CRC and R‐CRC may be influenced by the specific location within the colon itself. Further, we identified a potentially novel MYH11+ cancer‐associated fibroblast (CAF) subset predominantly enriched in L‐CRC. Moreover, we found that MYH11+ CAFs may promote tumour migration via interacting with macrophages, and was associated with poor prognosis in CRC. In summary, our study revealed the crucial role of MYH11+ CAFs in predicting a poor prognosis, thereby contributing valuable insights to the exploration of heterogeneity in L‐CRC and R‐CRC.