Fenghu Li, Xue Tian, Fan Mei, Yanjun Du, Lili Hu, Jiehui Li, Shengfa Su, Bing Lu
With the increase of clinical stage of cervical cancer, the positive expression rates of SIRT5 and TOP2A were significantly increased, and their high expression was related to the poor prognosis of patients. On the contrary, the negative expression rate of H2A increased with the advancing stage, and the prognosis of negative expression was worse. The above indicators had potential biomarker value for predicting the efficacy of cervical cancer treatment and the survival of patients. SIRT5 expression was negatively correlated with H2A and positively correlated with TOP2A. The potential regulatory mechanism among these three proteins warrant further in-depth investigation.
OBJECTIVE: To analyze the correlation between the expression of lysine deacetylase 5 (SIRT5), histone H2A and topoisomerase IIα (TOP2A) protein with clinical stage and survival in cervical cancer.
METHODS: The expression levels of SIRT5, H2A and TOP2A proteins were detected by immunohistochemical two-step method in paraffin-embedded tissue blocks from 65 patients with cervical cancer (21 cases of stage IB, 9 cases of stage IIA and 35 cases of stage IIIC1p). The expression distribution and positive rate of SIRT5, H2A and TOP2A proteins in tumor tissues of patients with different stages of cervical cancer were compared, and furthermore, survival analysis was conducted using Kaplan-Meier estimations and Cox regression modeling to pinpoint independent prognostic factors, along with the correlations among the expression levels of these three proteins.
RESULTS: The expression of SIRT5 and TOP2A increased significantly with the advancing clinical stage, whereas H2A expression showed a significant decrease with higher stage, and the difference was statistically significant (P < 0.05). As of April 2026, the median follow-up duration was 29 months (12-51 months). The 3-year overall survival (OS) and progression-free survival (PFS) of the SIRT5 negative group were significantly higher than those of the positive group (92% vs 49%, 90% vs 18%), and the differences were statistically significant (P < 0.05). In the H2A group, the 3-year OS and PFS of the positive group were significantly higher than those of the negative group (93% vs 64%, 86% vs 50%), and the differences were statistically significant (P < 0.05). The 3-year OS and FPS in the TOP2 A negative group were significantly higher than those in the positive group (87% vs 47%, 83% vs 19%), and the differences were statistically significant (P < 0.05). Multivariate Cox analysis identified SIRT5 positive expression (HR = 2.64, 95% CI: 1.08-5.60, P = 0.047) (HR = 2.24, 95% CI: 1.04-5.35, P = 0.004), TOP2A positive expression (HR = 2.96, 95% CI: 1.60-4.50, P = 0.018) (HR = 1.97, 95% CI: 1.29-4.13, P = 0.025) and H2A negative expression(HR = 0.29, 95% CI: 0.02-0.93, P = 0.032) (HR = 0.71, 95% CI: 0.08-0.98, P = 0.027) expression as independent predictors of OS and PFS. Spearman correlation analysis showed that the expression of SIRT5 protein was negatively correlated with the expression of H2A protein (r = -0.678, P = 0.000), and positively correlated with the expression of TOP2A (r = 0.652, P = 0.000).
CONCLUSION: With the increase of clinical stage of cervical cancer, the positive expression rates of SIRT5 and TOP2A were significantly increased, and their high expression was related to the poor prognosis of patients. On the contrary, the negative expression rate of H2A increased with the advancing stage, and the prognosis of negative expression was worse. The above indicators had potential biomarker value for predicting the efficacy of cervical cancer treatment and the survival of patients. SIRT5 expression was negatively correlated with H2A and positively correlated with TOP2A. The potential regulatory mechanism among these three proteins warrant further in-depth investigation.