ABSTRACT
Hodgkin's lymphoma (HL) is a hematological malignancy characterized by a minority of neoplastic cells outnumbered by tumor-associated macrophages (TAMs). The overexpression of the CD163 antigen by TAMs is considered to be a significant predictive biomarker for risk stratification. This is likely caused by a genetic single-nucleotide polymorphism (SNP) at the gene promoter. The aim of the present retrospective case-control study was to establish a gene expression profile of a specific biomarker for classical HL (CHL) in order to predict the outcome and survival of CHL patients in Saudi Arabia. The protein expression of CD163 on TAMs was studied using immunohistochemistry (IHC). A prognosis index was calculated for the CD163 protein to assess the risk stratification of CHL. Genotyping of selected SNPs of this antigen was performed for 100 CHL cases and controls. The analysis revealed that the CD163 protein expression level was significantly correlated with disease relapse (DR) and overall survival (OS). In addition, the CD163 index threshold (15.0) was found to be significantly correlated with the relapse rate. Among the studied CD163 SNPs, rs75608120 exhibited a significant correlation with the DR rate of CHL patients, but not with OS. The findings of the present study confirmed that CD163 is a specific marker for TAMs, and its overexpression by TAMs is significantly associated with relapse and reduced survival post-therapy. In addition, a new methodology of indexing CD163 protein expression for HL risk stratification was proposed. Thus, the present study identified a specific predictive molecular and antigenic biomarker for CHL prognosis.
ABSTRACT
In Hodgkin's lymphoma (HL), single nucleotide polymorphisms (SNPs) of specific DNA repair genes have been identified to have an important role in the risk of HL. Consequently, they may also serve an important role in HL prognosis and disease outcome. The present study aimed to define an SNP molecular profile, based on DNA repair genes mutations, as predictive biomarkers for the prognostic outcome of patients with Classical HL (CHL) in Saudi Arabia. Genotyping of selected SNPs located in selected DNA repair genes was performed on 100 CHL cases and an equivalent number of healthy controls. No significant associations between CHL disease relapse (DR) or overall survival (OS) and 4 DNA repair genes were observed, with the exception of xeroderma pigmentosum, complementation group G (XPG) repair gene SNP (rs17655), which revealed a statistically significant association with CHL patient survival (P=0.036). Accordingly, these data suggest that the XPG gene may be a useful predictive molecular genetic biomarker for CHL clinical outcome. The present study also provided valuable insights on the contribution of DNA repair genes in Saudi patients with CHL. To the best of our knowledge, we defined for the first time, a specific genetic pattern associated with CHL outcome was defined in the present study in Saudi patients.
