Exploratory Analysis of HMGB1 Genetic Variants and Their Potential Association with Lung Cancer Susceptibility and Chemotherapy Response in a Chinese Population.

INTRODUCTION: High-mobility group box 1 (HMGB1) protein plays a significant role in cancer development and treatment response. The current research on the role of HMGB1 in lung cancer and its treatment outcomes is limited and inconsistent. This exploratory study investigated the association between HMGB1 common genetic variants and lung cancer susceptibility, as well as cisplatin chemotherapy response, in a Chinese cohort. METHODS: The current study included 106 individuals diagnosed with lung cancer and 93 healthy subjects, all of whom were part of a Chinese population cohort. HMGB1 polymorphisms (rs1045411, rs1412125, rs2249825, and rs1360485) were genotyped using the TaqMan single-nucleotide polymorphism typing method. HMGB1 gene expression in the lung tissue of patients was quantified using real-time PCR. All patients were administered cisplatin, and their response to the drug was evaluated. All statistical analyses were performed using GraphPad Prism v10. RESULTS: The control group exhibited a higher frequency of heterozygous variants for HMGB1 polymorphisms rs1045411 (p = 0.01, odds ratio [OR] = 0.45) and rs1412125 (p = 0.03, OR = 0.46) than the patients. Moreover, the combined mutant genotypes for HMGB1 rs1045411 (p = 0.0001, OR = 0.15) and rs2249825 (p = 0.003, OR = 0.19) exhibited favorable responses to cisplatin treatment. Moreover, the wild-type variants of rs1045411 and rs2249825 exhibited higher HMGB1 expression than the mutants; however, this difference was not statistically significant. CONCLUSION: This preliminary investigation indicated potential associations between HMGB1 genetic variants and lung cancer susceptibility and treatment response. These exploratory findings necessitate further validation through larger multicenter studies incorporating functional assays to elucidate the biological significance and clinical utility of HMGB1 polymorphisms in the management of lung cancer.