Fig. 1

CircTMEM181 is associated with poor prognosis in HCC patients. a Changes in tumor size in six patients after anti-PD1 treatment, evaluated by iRECIST. The blue line represents PR (partial response, n = 3), and the orange line represents PD (progressive disease, n = 3). b Heatmap of circRNA expression in tumor tissue biopsies from HCC patients showing PR or PD after anti-PD1 treatment. c Schematic illustration of circTMEM181 formation (Top). Sanger sequencing shows the back-splice sites (Bottom). d A total of 60 paired HCC tumor tissues (T) and para-tumor normal liver tissue (PT) were subjected to qPCR to detect circTMEM181 expression. e, f Representative images of H&E staining and in situ hybridization analysis of circTMEM181 expression in HCC tumor tissue or para-tumor normal liver. Statistical results show a higher level of cicTMEM181 in HCC tumor tissue (T) than in the paired para-tumor normal liver (PT) (n = 204; paired t test, ***: p < 0.001). g, h Kaplan–Meier estimate of overall survival or cumulative recurrence in the cohort with different levels of cirTMEM181 (n = 204, logrank test). i Heatmap of 204 HCC patients with their clinicopathologic characteristics grouped by circTMEM181 expression (blue indicates the high or positive group of the characteristic; the red frame indicates microvascular invasion and shows significant positive correlation to circTMEM181). Forest plot of univariate or multivariable Cox proportional hazard regression indicates the impact of different characteristics on overall survival (OS)