Clinical relevance and function of HMGB1 gene polymorphism and expression in colorectal cancer.

Abstract

High HMGB1 levels contribute to the development and metastasis of tumors such as colorectal cancer (CRC). The current investigation sought to evaluate the association of a functional InDel polymorphism (rs34000982) on the HMGB1 gene with CRC susceptibility and tumor stage and the clinical relevance of HMGB1 gene expression. A total of 600 CRC patients and 600 healthy control individuals were genotyped by a polymerase chain reaction-polyacrylamide gel electrophoresis assay. The findings demonstrated that the rs34000982 Ins allele or Ins/Ins genotype was associated not only with reduced susceptibility to CRC, especially stage III-IV CRC (Ins vs. Del: OR = 0.65, 95%CI = 0.51-0.82, p < 0.001; Ins/Ins vs. Del/Del: OR = 0.29, 95%CI = 0.14- 0.60, p < 0.001), but also with tumor stage. CRC patients carrying the Ins allele or Ins/Ins genotype had a significantly lower risk of stage III-IV tumors (Ins vs. Del: OR = 0.69, 95%CI = 0.53- 0.91; Ins/Ins vs. Del/Del: OR = 0.41, 95%CI = 0.18-0.94). Functional research revealed that the rs34000982 Ins allele enabled hsa-miR-944 to interact with the 3' untranslated region of HMGB1. In addition, HMGB1 gene expression levels were associated not only with multiple immune cell infiltration, but also with multiple anti-CRC drug sensitivities. The current findings suggest that the HMGB1 rs34000982 polymorphism may serve as a marker of CRC susceptibility and progression in the Chinese population, and HMGB1 levels may serve as an anti-CRC drug sensitivity marker.