HLA class II polymorphisms as prognostic biomarkers for right and left-sided colon cancer

• Published in: The International journal of biological markers Vol. 39; no. 1; pp. 40 - 51
• Main Authors: Attia, Amani, Lagha, Awatef, Mezlini, Amel, Ghazouani, Ezzedine, Yacoubi-Loueslati, Besma, Namouchi, Imene
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.03.2024; Sage Publications Ltd
• Subjects: Antigens; Biomarkers; Colon cancer; Colorectal cancer; Drb1 protein; Genotyping; Haplotypes; Histocompatibility antigen HLA; Immunological tolerance; Malignancy; Medical prognosis; Metastases; Metastasis; Polymerase chain reaction; PCR-SSP; right-sided colon cancer; left-sided colon cancer; HLA-DRB1; HLA-DQB1
• ISSN: 0393-6155; 1724-6008; 1724-6008
• DOI: 10.1177/03936155231224469

Background Colon cancer (CC) is one of the most common malignancies worldwide. Characterization of new prognostic biomarkers for right-sided CC (RCC) and left-sided CC (LCC) may contribute to improving early detection. An association of human leukocyte antigens class II (HLA-II) with the predisposition to CC was suggested. Aim of the study We evaluated the association of DRB1 and DQB1 with the risk of LCC and RCC. Patients and methods Our study comprised 93 CC patients and 100 healthy controls. Genotyping of HLA class II alleles were performed by the Polymerase Chain Reaction Sequence-Specific Primers (PCR-SSP). Results DRB1*03 was positively associated with CC. In contrast, DRB1*11, DRB1*13, DQB1*03, and DQB1*05 were negatively linked to CC. Haplotype analysis revealed that DRB1*04-DQB1*04 and DRB1*09-DQB1*02 were positive, while DRB1*01-DQB1*05, DRB1*04-DQB1*03, DRB1*07-DQB1*02, DRB1*11-DQB1*03, DRB1*11-DQB1*05, and DRB1*13-DQB1*06 were negatively associated with CC. For sigmoid CC, DRB1*13, DRB1*11, and DQB1*05 were negative, while DRB1*04-DQB1*02, and DRB1*07-DQB1*03 were positively associated. DRB1*03 and DRB1*04-DQB1*04 were positive, while DRB1*11 and DQB1*03 were negatively linked to RCC. According to the LCC, DRB1*07, DRB1*11, DQB1*03, DQB1*05, and DRB1*07-DQB1*02 were negative. In contrast, DRB1*09-DQB1*02 was positively associated with LCC. Stratified analysis revealed that DRB1*11 is associated with higher risk of metastasis in CC and sigmoid CC, and tolerance to treatment in RCC. DQB1*03 was associated with lymph-node invasion in CC. Conclusion DRB1 and DQB1 polymorphisms could be used as future biomarkers for the early detection of subjects at a higher risk of developing RCC and LCC, metastasis in sigmoid CC, and tolerance to treatment in RCC.