REV7 Expression Is Associated with Tumor Cell Growth and Cisplatin Resistance in Gallbladder Adenocarcinoma

Abstract – Introduction: REV7 functions in various biological processes, including the DNA damage response. REV7 expression has been linked to the prognosis and chemoresistance in several human cancers. This study investigated the significance of REV7 in gallbladder adenocarcinoma (GBAC). Methods: REV7 expression was examined immunohistochemically in 77 resected GBAC specimens, and its association with clinicopathological features was analyzed. REV7-depleted GBAC cell lines were established, and the biological effects of REV7 depletion were evaluated. Results: High REV7 expression in GBAC tissues correlated with increased cell proliferation, as assessed by Ki-67 labeling indices (p < 0.001), and was associated with a trend toward shorter overall survival (p = 0.070) and significantly shorter post-progression survival (p = 0.035). REV7-knockout and REV7-knockdown cell lines derived from NOZ and G415 GBAC cells (NOZ-KO and G415-KD, respectively) showed reduced proliferation and increased sensitivity to cisplatin; however, REV7 depletion did not affect cell migration and invasion. Reintroduction of REV7 into NOZ-KO cells restores chemoresistance. Furthermore, RNA sequencing analysis comparing wild-type NOZ and NOZ-KOs revealed that REV7 inactivation downregulates genes involved in the DNA damage response. Conclusion: REV7 may contribute to tumor progression and chemoresistance in GBAC and may serve as a prognostic biomarker and molecular target for GBAC management.