Role of a novel circulatory RNA‐based biomarker panel expression in ovarian cancer

Abstract

Ovarian cancer (OC) is considered the sixth commonest cancer affecting women globally. We choose novel integrated specific ovarian cancer RNA biomarker panel; pellino E3 ubiquitin protein ligase family member 3 (PELI3) gene expressions along with its selected epigenetic regulators (microRNA (miR-361-3p) and long noncoding RNA (lncRNA RP5-837J1.2) by bioinformatic methods. Then, differential expressions of the selected panel in the sera of 50 OC patients, 42 cases with benign ovarian lesions, and among 45 controls were determined using realtime polymerase chain reaction quantitative (qRT-PCR). Furthermore, their expression was measured also in malignant ovarian tissues and adjacent nontumor tissues in 23 of 50 OC patients by quantitative qRT-PCR. The current study reported, for the first time, upregulation of serum lncRNA RP5-837J1.2 with concomitant downregulation of miR-361-3p and PELI3 mRNA in malignant group compared with benign and controls groups. There were associations of serum lncRNA RP5-837J1.2 with the affected ovary and worse International Federation of Gynecology and Obstetrics staging; associations of miR-361-3p with tumor size, grade, stage, and presence of metastasis; as well as associations among PELI3 mRNA expression and tumor size, grade, stage, and presence of metastasis among the OC group. In tumor tissues, miR-361-3p and PELI3 mRNA levels were at a higher level than that of nontumor tissues; however, tumor tissue showed lower level of lncRNA RP5-837J1.2 compared to normal tissue. There were positive correlations between serum and tissue level of RNA RP5-837J1.2, miR-361-3p, and PELI3 mRNA, but they did not reach statistical significance. Receiver operating characteristics curve analyses showed that lncRNA RP5-837J1.2, miR-361-3p, and PELI3 mRNA expression levels can discriminate among OC patient, cases with benign Abbreviations: AUC, Area under the curve; BMI, body mass index; CA125, cancer antigen 125; CEA, carcinoembryonic antigen; FIGO, International Federation of Gynecology and Obstetrics; IRAK1, interleukin-1 receptor-associated kinase 1; lncRNA, long noncoding RNA; NSCLC, non-small cell lung cancer; OC, Ovarian cancer; PELI3, Pellino E3 ubiquitin protein ligase family member 3; qRTPCR, polymerase chain reaction; ROC, receiver operating characteristic; RQ, relative quantity; TLRs, Toll-like receptors; TNF, tumor necrosis factor; TRAF6, TNF receptor-associated factor 6 complex.

Candidate RNA biomarkers in biofluids for early diagnosis of ovarian cancer: A systematic review

“…Even though CA125 protein is currently the standard diagnostic marker for ovarian cancer, only one third of the studies directly compare the performance of (combinations of) RNA markers to CA125. Individual levels of serum EV miR-145 [15], serum EV miR-200b [15], plasma circBNC2, and serum RPS-8337J1.2 [25] resulted in a higher AUC than that of the CA125 protein. The combination of miR-205 and let-7f was also able to outperform CA125 [42], just like a neural network based on 14 miRNAs [46].…”

“…Although the extracellular transcriptome of human biofluids is complex and diverse, most liquid biopsy studies in this field focused on miRNAs (30/36). Only two studies looked into circRNAs [23,27], two studies investigated mRNAs [18,38], one study looked into long noncoding RNAs (lncRNAs) [45] and one study looked into a combination of one miRNA, one lncRNA and one mRNA [25]. Surprisingly, RNA sequencing for unbiased biomarker discovery is rarely used in the reported literature on RNA biomarkers for early diagnosis of ovarian cancer.…”

“…Only three studies used RNA sequencing in combination with RT-qPCR to detect potential biomarkers [14,41,46]. In 25 studies the biomarker detection is based on RT-qPCR only, in five studies both a miRNA microarray and RT-qPCR were used [32,34,35,37,42] and in three studies only a miRNA microarray was used [13,19,25].…”

Ferroptosis-Related Long Noncoding RNAs as Prognostic Biomarkers for Ovarian Cancer

“…Serum samples were collected from clinical patients with OC, those with benign ovarian disease, and controls. Then, the differential gene expression levels in the serum were detected using RT–PCR methods ( 46 ). The results showed that serum lncRNA RP5 expression was significantly upregulated in the malignant tumor group compared with the benign and control groups.…”

“…The lncRNA RP5 expression was lower in malignant ovarian tissue and adjacent nontumor tissues from patients with OC than in normal tissues. Furthermore, the operator characteristic curves showed that the expression values of lncRNA RP5 obviously distinguished the patients with OC from patients with benign masses and control patients, with an accuracy rate of 96% ( 46 ). These results indicate that these new diagnostic biomarker RNAs could help diagnose OC and could be of great importance for the early detection and treatment of clinical tumors.…”