Unlocking the potential of serum exosomal PIWI-interacting RNAs as diagnostic biomarker for endometrial cancer

Endometrial cancer is a common gynecological cancer with a rising incidence, yet effective non-invasive early diagnostic methods are lacking. Recent findings indicate that tumor-derived exosomal cargo, including PIWI-interacting RNAs (piRNAs), may serve as promising cancer-specific biomarkers. Our study investigates the potential of serum-derived exosomal piRNAs for early detection of endometrial cancer.

Biomarker development involves 3 phases with independent patient cohorts. In the discovery phase, small RNA sequencing identified candidate exosomal piRNAs from serum samples of 5 healthy controls and 6 patients with endometrial cancer. In the training phase, a serum exosomal piRNA panel was created using receiver operating characteristic curve, logistic regression, a random forest algorithm, and the DeLong test. In the validation phase, we verified the diagnostic performance of the 3piRNA_panel using the receiver operating characteristic curve.

In validation, the 3piRNA_panel (hsa_piR_009183, hsa_piR_014592, and hsa_piR_006767) showed high diagnostic accuracy for endometrial cancer, with an area under the curve of 0.942. It distinguished stage IA endometrial cancer from healthy controls with an area under the curve of 0.977 and was effective in patients with normal CA125 levels. It also potentially differentiated stage IA endometrial endometrioid carcinoma from atypical endometrial hyperplasia. A post-operative decrease in panel scores was observed in a limited subset of paired samples. The expression of hsa_piR_014592 was significantly associated with aggressive histopathological types, ≥50% myometrial invasion, substantial lymphovascular space invasion, lymph node metastasis, p53 mutation, and G3 endometrial endometrioid carcinoma.

Our novel non-invasive serum exosomal piRNA panel demonstrated clinical potential for the early detection of endometrial cancer.