Expression of MHC Class I Molecules (HLA-A, -B, -C, -E, -F, -G, and -J) Decreases From Early to Late Stage in Ovarian Cancer

Abstract

Problem

Interferon-ε (IFNε), which is highly abundant in the epithelium of the female reproductive tract (FRT), is a recently identified tumor suppressor for ovarian cancer. IFNε induces the expression of certain HLA class I family members in HGSOC (high-grade serous ovarian cancer), and its expression is lost during ovarian tumorigenesis. However, tumor stage–dependent expression of HLA class I family members in ovarian cancer has not been previously studied.

Method of Study

Data analysis and visualization were performed using various gene expression and transcriptomics datasets in the R statistical programming environment.

Results

We found that the expression of HLA-A, -B, -C, -E, -F, -G, and -J is lower in late stage ovarian tumors compared to early-stage tumors. The total expression of HLA class I family members decreases with age in ovarian cancer. Furthermore, we showed that the expression of some IFN-regulated genes, which were shown to be upregulated by IFNε, decreases from early to late stage in ovarian cancer, in parallel to the loss of IFNε expression in ovarian tumorigenesis and possibly in tumor progression. We also found that breast tumors (another hormonally driven cancer) with positive progesterone receptor status have lower IFNε mRNA expression compared to those with negative PR status. Besides, we reported that breast tumors with positive estrogen receptor (ER) status have lower expression of IFNε compared to those with negative ER status.

Conclusions

Combined, this study points that the decrease in the expression of IFNε, HLAs, or some other IFNε-regulated genes during ovarian cancer progression might contribute to worse prognosis in advanced disease.