br To date few studies have
To date, few studies have investigated whether LHCGR and hCG expression levels correlate in ovarian cancer tissues. Szczerba et al.  did previously demonstrate an inverse association between increased hCG levels and lowered LHCGR protein expression levels in an OVCAR3 ovarian-cancer cell model; however, this was not statistically sig-nificant. Nevertheless, these findings were consistent with previously generated low-density-array data, which supports the hypothesis that LH-mediated LHCGR activation decreases the invasiveness and migra-tion of ovarian cancer GSK 3 .
Based on these collected findings, the present study investigated whether hCG and LHCGR expression levels were correlated in tissue samples from 139 patients with EOC, and/or whether they were asso-ciated with patient clinicopathological characteristics. The results of the conducted RT-PCR analyses revealed significantly increased and decreased hCG and LHCGR mRNA levels, respectively, in cancerous compared to those in normal ovarian tissues, and these findings were Pathology - Research and Practice 215 (2019) 748–754
supported by the results of the conducted western blot analyses. Furthermore, high hCG expression was shown to be associated with EOC progression and a worsened patient prognosis, as indicated by more advanced FIGO tumor stages, and increased rates of tumor me-tastasis. Similarly, low LHCGR expression level was found to correlate with advanced FIGO tumor stages, and increased rates of tumor me-tastasis. However, numerous studies have shown that the diﬀerent histological types of ovarian carcinoma are profoundly diﬀerent dis-eases, our studies found that the expression of hCG or LHCGR was not significantly associated with the histological types of EOC. Moreover, the OS rate experienced by patients that exhibited tumors with high hCG, or low LHCGR expression levels was lower than that experienced by patients that exhibited tumors with low hCG or high LHCGR ex-pression. Thus, hCG and LHCGR expression levels may be promising potential prognostic markers for patients with EOC, given that they correlate consistently with patient disease stages, rates of metastasis, and OS.
hCG may aﬀect the expression of LHCGR in luteal cells, with a de-crease in receptors reducing the binding activity of hCG . However, the present study found a significant negative relationship between hCG and LHCGR expression levels in the analyzed tissue samples, suggesting that mechanisms other than LHCGR may regulate hCG activity in this context.
In conclusion, increased hCG expression and low LHCGR expression levels in ovarian cancer tissues are positively associated with ovarian cancer progression and metastasis, and thereby, with a worsened pa-tient OS rate. Thus, both hCG and LHCGR should be investigated as potential novel markers or therapeutic targets for ovarian cancer. For example, LHCGR-targeted therapeutic agents may be a promising ap-proach to reduce mortality and morbidity in ovarian cancer, while in-curring less toxic eﬀects in patients. Further research is needed to both elucidate the mechanisms by which hCG and LHCGR modulate ovarian cancer progression and evaluate their potential clinical value as ther-apeutic targets.
Conflict of interest
No potential conflicts of interest were disclosed.
We thank the Laboratory of Immunology, Nantong University, China and Clinical Medicine Research Center of Aﬃliated Hospital of Nantong University for technical assistance. This work was supported by the Nantong Applied Research Project (MS12015006 and MS12017008-2). The manuscript was edited by the professional lan-guage editing service Elsevier Webshop.
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TUMORIGENESIS AND NEOPLASTIC PROGRESSION
Association of High miR-182 Levels with Low-Risk Prostate Cancer
Bethany Baumann,* Andrés M. Acosta,* Zachary Richards,* Ryan Deaton,* Anastasiya Sapatynska,* Adam Murphy,y Andre Kajdacsy-Balla,* Peter H. Gann,* and Larisa Nonn*