Integrated analysis of single-cell and bulk RNA sequencing identifies APOC1 as a biomarker and therapeutic target for G0/G1 cell cycle arrest in cholangiocarcinoma.

Abstract

Cholangiocarcinoma is characterized by its high malignancy, frequent recurrence and insensitivity to conventional radiotherapy and chemotherapy. This resistance may be associated with the presence of cells in the G0/G1 arrest phase within the cancer. Cancer cells in the G0/G1 phase are resistant to therapies targeting actively dividing cells, allowing them to evade conventional adjuvant treatments and survive. When conditions become favorable, these quiescent cells can re-enter the cell cycle, proliferate and potentially contribute to cancer recurrence. However, the biomarkers for identifying cells in the G0/G1 arrest phase within cholangiocarcinoma and the molecular mechanisms inducing G0/G1 arrest remain unclear. In our study, we first identified APOC1 as a characteristic gene for G0/G1 phase arrest in cholangiocarcinoma through bulk RNA sequencing (bulkRNA-seq). We then used single-cell RNA sequencing(scRNA-seq) for cell cycle inference and localized the expression peaks of APOC1 to verify its active cell cycle phase. Our experiments demonstrated that APOC1 can induce G0/G1 phase arrest in cholangiocarcinoma cells by inhibiting the Wnt/β-catenin signaling pathway, thereby suppressing cell proliferation, migration and invasion. This suggests that APOC1 may serve as a key regulatory factor and an important biomarker for cells in the G0/G1 phase of cholangiocarcinoma.