MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

Abstract

ObjectiveTo evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival.Patients and MethodsWe conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong).ResultsExpression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P<.001 for both). In HGSOC, strong MyD88 expression was modestly associated with shortened overall survival (hazard ratio [HR], 1.13; 95% CI, 1.01–1.26; P=.04) but was also associated with advanced stage (P<.001). The expression of TLR4 was not associated with survival. In low-grade serous ovarian cancer (LGSOC), strong expression of both MyD88 and TLR4 was associated with favorable survival (HR [95% CI], 0.49 [0.29–0.84] and 0.44 [0.21–0.89], respectively; P=.009 and P=.02, respectively).ConclusionResults are consistent with an association between strong MyD88 staining and advanced stage and poorer survival in HGSOC and demonstrate correlation between strong MyD88 and TLR4 staining and improved survival in LGSOC, highlighting the biological differences between the 2 serous histotypes.

Plasma tRNA Fragments Derived from 5′ Ends as Novel Diagnostic Biomarkers for Early-Stage Breast Cancer

“…MYD88, a toll-like receptor signaling adaptor protein, is critical in the development of pancreatic cancer, epithelial ovarian cancer, and bladder cancer. [40][41][42] Finally, the roles of these tRFs in the development of BC were further confirmed by analyzing their target genes, and they were considered to serve as potential biomarkers for the detection of EBC.…”

The suppressive role of miR-362-3p in epithelial ovarian cancer

“…To investigate the underlying mechanism of miR-362-3p in OC, we tested the potential target gene of miR-362-3p, MyD88. A previous study showed strong MyD88 staining and poor survival in low-grade serous ovarian cancer [ 26 ]. The online software Targetscan showed that MyD88 is a potential targeted gene.…”

“…In another study, it showed that in high-grade serous ovarian carcinomas (HGSOCs). Interesting, the function of MyD88 seemed have related with the grade of serous ovarian cancer [ 26 ]. It showed that strong MyD88 expression was modestly associated with shortened overall survival, and in low-grade serous ovarian cancer (LGSOC), strong expression of both MyD88 and TLR4 was associated with favorable survival.…”

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“…TLR4 was the first member of the TLR family to be discovered, by Medzhitov et al in 1997 (14). It was verified that TLR4 is expressed in many types of tumors, such as hepatocellular carcinoma, glioblastoma, lung, breast, ovarian and colon cancers as well as melanoma (15)(16)(17)(18)(19)(20)(21). OSCC was also among the tumors that highly express this receptor (22)(23)(24)(25).…”