17P - Identification PD-L1-associated lncRNA biomarkers for immunoregulation in ovarian cancer

Background

Ovarian cancer is the most lethal gynecological malignancy worldwide and is known to have a poor prognosis among gynecological cancers. Recently, PD-1/PD-L1 inhibitors have demonstrated promising clinical outcomes in the treatment of OC. However, only about 20% of patients respond to these therapies, highlighting the need for improved patient selection. LncRNAs are significantly involved in tumor proliferation, apoptosis, migration, and metastasis and have significant associations with immune cell infiltration and the cancer cell response to anti-PD-1 immunotherapy in various tumors. Based on reports that immune-related lncRNAs play a role in regulating the PD-1/PD-L1 mechanism, this study aims to identify predictive biomarkers for ovarian cancer.

Methods

We analyzed the mRNA and protein levels of PD-L1 in OC patient tissues and classified them into high and low PD-L1 expression groups. We performed lncRNA microarray analysis on the classified groups. As a result, we identified MIR4435-2HG as lncRNA associated with PD-L1 overexpression. Furthermore, MIR4435-2HG knockdown were conducted. Other features, including cell growth, apoptosis, migration and invasion were also analyzed.

Results

A positive correlation between PD-L1 and MIR4435-2HG was observed in both OC tissues and cell lines. Knockdown of MIR4435-2HG in OC cell lines resulted in decreased PD-L1 expression and induce cellular apoptosis and inhibit cell migration and invasion. Moreover, GO analysis revealed that MIR4435-2HG is associated to immune-related genes.

Conclusions

Therefore, this study suggests that the lncRNA MIR4435-2HG associated with PD-L1 may be used as a predictive biomarker and therapeutic target in ovarian cancer.

Legal entity responsible for the study

The Catholic University of Korea, Industry-Academic Cooperation Foundation.

Funding

The National Research Foundation of Korea (NRF).

Disclosure

All authors have declared no conflicts of interest.