Association of SIRT6 Expression With Risk of Pneumonitis Induced by Radiotherapy in Cancer Patients

Authors

Fengyuan Yu
Zheng Gong
Yuan Li
Danial F Naseem
Chen Li
Miaowei Wen
Bingying Zhao
Zhezhe Xu
Shanshan Zhang
Rukun Zang
Ailu Wu
Qingxin Han
Shuhui Wu
Hongwei Li
Yipeng Song

Publication Date

6-1-2025

Journal

Molecular Carcinogenesis

Abstract

Thoracic tumours represent a significant proportion of malignant cancers. While radiotherapy (RT) improves prognosis, it can also lead to side effects such as radiation-induced pneumonitis (RP). Since SIRT6 is involved in DNA repair, energy metabolism and inflammation, this study aims to investigate the expression of SIRT6 in lymphocytes as a potential biomarker and therapeutic target for RP. This study included 170 patients diagnosed with thoracic tumours, all of whom underwent thoracic RT. RP was evaluated and classified as severe RP (SRP) and lower as non-severe RP (NSRP). Analyses were performed using SPSS version 26.0 and the R. Among 170 patients in this study, 124 developed NSRP, and 46 experienced SRP. The univariate analysis showed that SIRT6 expression (cOR, 0.33, 95%CI, 0.18-0.97 before RT and 0.31, 0.19-0.98 after RT), clinical factors, dosimetric parameters and haematological/serological parameters were associated with SRP before and after RT. Our multivariable logistic regression showed that SIRT6 expression was significantly associated with risk of SRP before (aOR, 0.32, 95%CI, 0.15-0.96) and after RT (aOR, 0.32, 95%CI, 0.18-0.99) after adjustment with other confounders. Moreover, the receiver operating characteristic curve analysis revealed that the combined multivariable model exhibited superior predictive capability compared to any single predictor (overall AUC, 0.93, 95%CI, 0.90-0.97 before RT and AUC, 0.91, 95%CI, 0.87-0.96 after RT). The expression of SIRT6 alone or in combination with other risk factors was associated with an increased risk of SRP, suggesting a novel approach for the prevention and treatment of radiation pneumonitis in clinical practice.

Keywords

Humans, Sirtuins, Female, Male, Radiation Pneumonitis, Middle Aged, Aged, Risk Factors, Adult, Prognosis, Thoracic Neoplasms, Radiotherapy, Lymphocytes, ROC Curve, lymphocyte, radiation pneumonitis, radiotherapy, SIRT6, thoracic tumours

DOI

10.1002/mc.23900

PMID

40170513

PMCID

PMC12074565

PubMedCentral® Posted Date

4-1-2025

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes