Implication of Soluble HLA-G and HLA-G +3142G/C Polymorphism in Breast Cancer Patients Receiving Adjuvant Therapy in Tanzania

Abstract

Background: During cancer growth, immunosuppressive microenvironment is created that enables tumour cells to evade an eliminative immune response and hence manage to grow into malignancy. HLA-G, existing as either membrane-bound (mHLA-G) or soluble (sHLA-G) molecule is thought to be immunosuppressive and produced more by tumor cells. The +3142G/C polymorphism in HLA-G gene affects its expression, and G allele is considered to be a protective mutant allele associated with less expression of HLA-G. The implication of HLA-G in cancer development has been reported in different cancers and populations. But, its implication in most African populations has not yet been investigated. The aim of this study was to determine the possible associations of soluble HLA-G and HLA-G +3142G/C SNP with breast cancer. Materials and Methods: 75 breast cancer patients and 84 normal controls were recruited in this study. The genotyping of HLA-G +3142G/C polymorphism was determined by LightSNiP typing assay using quantitative Real-Time PCR and sHLA-G levels were determined by ELISA. Results: The sHLA-G levels were significantly lower in breast cancer patients than in controls (p<0.001). Also, they were significantly lower in mastectomized patients compared to non-mastectomized patients (p=0.018). The ROC analysis revealed a significant ability of sHLA-G to differentiate breast cancer patients versus normal controls (AUC=0.697, 95% CI= 0.619-0.767, p<0.001) and identify mastectomized patients (AUC=0.667, 95% CI= 0.549 to 0.772, p=0.041). The assessment of +3142G/C polymorphism revealed a relatively similar distribution of frequencies of genotypes and alleles between breast cancer patients and normal controls (p>0.05) and was neither associated with sHLA-G levels. Conclusion: While the +3142G/C SNP was found not to be relevant to breast cancer, the changes of sHLA-G levels in response to medical interventions such as mastectomy may be translated into its potential prognostic utility for breast cancer. More studies are needed to provide clear evidence of sHLA-G as a diagnostic and prognostic marker of breast cancer in Tanzania.

HLA-G and single nucleotide polymorphism (SNP) associations with cancer in African populations: Implications in personal medicine

“…Though, the few patients whose sHLA-G levels remained high were found to have had their cancers metastasized. Similarly, in our recent study, 82 we found a significantly lower amount of sHLA-G among breast cancer patients who had undergone mastectomy as compared to those who had not. Rutten et al 78 found a significant decline in sHLA-G levels following chemotherapy treatment of high-grade ovarian cancer, and the sHLA-G increased to almost the initial levels following recurrence.…”

The Potential of Soluble Human Leukocyte Antigen Molecules for Early Cancer Detection and Therapeutic Vaccine Design

“…In addition to thyroid cancer, plasma sHLA-G levels were also lower in breast cancer patients. However, these were non-treatment-naïve samples, thus the relationship between sHLA-G and breast cancer is unclear [ 44 ].…”

“…Extending upon this, the number of studies that perform a receiver operating characteristic (ROC) analysis (plotting the relation between sensitivity and specificity) to assess the discriminative power of sHLA as a biomarker is limited. Although only partially informative due to the lack of proper non-malignant control groups, the described area under the curve (AUC) for sHLA-G to discriminate cancer patients from healthy controls was significantly different from chance (AUC = 0.5) in all reporting studies and ranged from 0.6 to 0.842 [ 33 , 35 , 36 , 39 , 44 , 50 ]. From these studies, three report on a good discriminative power of sHLA-G between malignancy and other, non-malignant diseases, although two of those mixed non-malignant control samples with healthy controls for ROC analysis [ 35 , 36 , 39 ].…”