Relevance of HLA-DP/DQ and ICAM-1 SNPs among Ovarian Cancer Patients

Abstract

BackgroundOvarian cancer is one of the most lethal gynecological malignancies and the fifth leading cause of cancer deaths among women. The high mortality rate is largely attributed to its diagnosis in advanced stages. Poor prognosis of ovarian cancer is usually due to the lack of specific or effective screening and diagnostic methods for identifying early-stage disease.AimOur study aimed to study the role of HLA-DP, HLA-DQ, and ICAM-1 SNPs in diagnosis and/or prognosis of ovarian tumorsSubjects and methodsThe current study was conducted on 60 patients with ovarian tumors (benign, borderline, and malignant) and 20 healthy volunteers. Genotyping of HLA-DP rs3077, HLA-DQ rs3920, and ICAM-1 rs1437 SNPs was done using 5′ nuclease assay.ResultsWe found significant association of HLA-DP rs3077 AA, HLA-DQ rs3920 GG, ICAM-1 rs1437 CC, and CT genotypes with increased risk of ovarian cancer (OR = 43.5, 6, 25, and 2.6, respectively). In addition, HLA-DQ rs3920 and ICAM-1 rs1437 alleles vary significantly among different types of ovarian cancer (P = 0.003 and 0.001, respectively).ConclusionHLA-DP rs3077, HLA-DQ rs3920, and ICAM-1 rs1437 SNPs could help in the diagnosis and prognosis of ovarian cancer.

Genetic Profiles Associated with Chemoresistance in Patient-Derived Xenograft Models of Ovarian Cancer

“…This suggests that these MHC class II molecules have an important effect on the mechanism underlying cancer chemoresistance. This result was in agreement with other studies, which found that the MHC complex played a main role in ovarian immunology and that both HLA class I and II molecules contributed to resistance to treatment [15,16]. This result was further validated by the TCGA database, which predicted that patients with high expression of HLA-DPA1 would be more CR to initial chemotherapy.…”

Epigenetic modifiers upregulate MHC II and impede ovarian cancer tumor growth

“…MHC class II antigen DP Alpha 1 ( HLA-DPA1 ) is a MHC class II paralogue. Single nucleotide polymorphisms within HLA-DP have been significantly associated with OVCA incidence and increased tumor aggressiveness [ 22 ]; therefore, we selected this locus to evaluate. Treatment with azacytidine or entinostat resulted in significant increases in HLA-DPA1 expression relative to the vehicle group (p = 0.0135 and 0.0053, respectively).…”

Utilizing iVariantGuide for Variant Assessment of Next‐Generation Sequencing

“…Of interest was the antigen processing and presentation pathway, in which we were able to identify several high‐impact mutations in our cohort in genes including HLA‐DRB5 and HLA‐DRB1 . Human leukocyte antigen (HLA)‐class I and II haplotypes have been associated with the pathogenesis of ovarian and breast cancer (Ghazy & El‐Etreby, ). It would be prudent to determine what truncations are being held in the HLA class I and II genes that cross reference with other databases such as the Human Gene Mutation Database.…”