RESUMO
Background: To evaluate prognostic value of WTAP levels in tumor and paired adjacent non-neoplastic liver tissues (PANLT) for cases of hepatitis B virus (HBV)-positive Asian small hepatocellular carcinoma (sHCC) patients who received curative partial hepatectomy. Method: The investigation with two external cohorts were included. Associations between hazard risk of recurrence and continuous WTAP levels were investigated with restricted cubic spline models. Cox and inverse probability weighting models were established for survival analysis. Based on interaction effects, further stratification analysis was performed. Landmark analysis was employed to analyze cases of late recurrence. Finally, sensitivity analysis was performed to assess unmeasured confounders. Findings: In an investigation cohort of 307 patients, restricted cubic spline models indicated that hazard risk of recurrence increases with elevated WTAP levels for sHCC and PANLT. However, using Cox and inverse probability weighting models, no significant differences were observed in recurrence-free survival (RFS) between groups with different WTAP levels in sHCC. Multivariate analysis showed that patients with high PANLT WTAP levels had significantly worse RFS (HR 1.567, 95% CI 1.065-2.307; p = 0.023). Based on the significant interaction effect between WTAP levels in sHCC and PANLT, stratification analysis revealed that recurrence risk is more pronounced in patients with high WTAP levels in both PANLT and sHCC. Landmark analysis showed that late recurrence was more likely to occur in patients with high PANLT WTAP levels (HR 2.058, 95% CI 1.113-3.805; p = 0.021). Moreover, the detrimental effects of elevated PANLT WTAP levels on RFS were validated with two external cohorts. Sensitivity analysis confirmed the robustness of results. Conclusion: Increased PANLT WTAP expression levels independently predict high recurrence risk in HBV-positive Asian sHCC patients. Both tumor tissues and PANLT need to be considered together in future clinical practice to obtain a more comprehensive and accurate evaluation for recurrence risk.
RESUMO
The development of programmed cell death-1 inhibitor (PD-1) has shed light on the treatment of tumors with deficiencies in DNA mismatch repair system or microsatellite instability (dMMR/MSI). However, predicting the subset in this group that will benefit from PD-1 blockade remains a challenge. In this study, we aimed to investigate the relationship between the degree of microsatellite instability and the responses to anti-PD-1 immunotherapy. 33 patients with colorectal adenocarcinoma who had a known MSI status and received anti-PD-1 immunotherapy were included. PCR results for MSI of the whole cohort were collected and treatment response was evaluated. Our data indicated that objective response rate (ORR) in instability-high group (instability loci ≥ 3) was significantly higher than ORR in instability-intermediate group (13/16 versus 6/17, P = 0.008). Besides, patients in instability-high group had significant longer progression-free survival (log-rank test, P = 0.004), and a significant increase in T lymphocyte infiltration and cytolytic activity in tumors. Future study might implement the intensity of microsatellite instability for more delicate selection for anti-PD-1 therapy in patient with dMMR/MSI-H tumors.
