Up-regulation of Cuproptosis-related lncRNAS in Patients Receiving Immunotherapy for Metastatic Clear Cell Renal Cell Carcinoma Indicates Progressive Disease.

Background/aim: Clear cell renal cell carcinoma (ccRCC) represents the most common type of renal cancer. When resectable, nephrectomy is the only radical treatment for ccRCC, however metastasis is already present at 30% of the patient population. Although great progress has been made in the field of targeted therapy with the emergence of immune checkpoint inhibitors (ICIs) the cure of metastatic ccRCC (mccRCC) remains far from achieved. Additionally, the need of biomarkers capable of predicting their therapeutic efficacy with the aim to ameliorate patient treatment and management is crucial. This study aimed to investigate potential changes in the expression of 3 cuproptosis-related lncRNAs, FOXD2-AS1, MINCR, LINC02154, in the blood of mccRCC patients that receive ICI-based treatments and whether these changes could be used to distinguish patients with clinical benefit (CB) from patients with progressive disease (PD).

Materials and methods: Peripheral blood from 31 mccRCC patients was obtained, prior to administration of ICI-immunotherapy. Using the RECIST criteria patients were subdivided into CB and PD groups. The fold change of FOXD2-AS1, MINCR, LINC02154 was evaluated using qRT-PCR.

Results: The tested lncRNAs showed an increase in peripheral blood with the most notable up-regulation in FOXD2-AS1 and LINC02154 (fold change of 3.7 and 3.8 respectively), followed by MINCR, (fold change of 2.6) in the PD patient group.

Conclusion: Cuproptosis-related lncRNAs FOXD2-AS1, MINCR, LINC02154 show promise for the prediction of patient response (CB vs. PD) in ICI-based therapeutic schemes in patients with mccRCC.