A Novel PiRNA Enhances CA19-9 Sensitivity for Pancreatic Cancer Identification by Liquid Biopsy

Abstract

Pancreatic cancer is one of the deadliest tumours worldwide, and its poor prognosis is due to an inability to detect the disease at the early stages, thereby creating an urgent need to develop non-invasive biomarkers. P-element–induced wimpy testis (PIWI) proteins work together with piwi-interacting RNAs (piRNAs) to perform epigenetic regulation and as such hold great potential as biomarkers for pancreatic cancer. PIWIL2 and PIWIL4 are associated with better prognosis, while PIWIL1 and PIWIL3 involvement appears to be associated with carcinogenesis. We aimed to discover PIWIL3- and PIWIL4-modulated piRNAs and determine their potential mechanisms in pancreatic cancer and the clinical implications. PIWIL3 or PIWIL4 was downregulated in pancreatic cancer-derived cell lines or in a non-tumour cell line. Differentially expressed piRNAs were analysed by next generation sequencing of small RNA. Nine fresh-frozen samples from solid human pancreases (three healthy pancreases, three intraductal papillary mucinous neoplasms, and three early-stage pancreatic cancers) were included in the sequencing analysis. Two piRNAs associated with PIWIL3 (piR-168112 and piR-162725) were identified in the neoplastic cells; in untransformed samples, we identified one piRNA associated with PIWIL4 (pir-366845). After validation in pancreatic cancer-derived cell lines and one untransformed pancreatic cell line, these piRNAs were evaluated in plasma samples from healthy donors (n = 27) or patients with pancreatic cancer (n = 45). Interestingly, piR-162725 expression identified pancreatic cancer patients versus healthy donors in liquid biopsies. Moreover, the potential of the serum carbohydrate antigen 19-9 (CA19-9) biomarker to identify pancreatic cancer patients was greatly enhanced when combined with piR-162725 detection. The enhanced diagnostic potential for the early detection of pancreatic cancer in liquid biopsies of these new small non-coding RNAs will likely improve the prognosis and management of this deadly cancer.

PIWI-interacting RNA-17458 is oncogenic and a potential therapeutic target in cervical cancer

“…Although there are a lot of reports about the various biological functions of piRNAs in occurrence and development of cancer 17 - 20 , the relationship between piRNAs and CC is not well known. It has been shown that piRNA-36712 was low expressed in breast cancer than in matched controls and its overexpression restrains progression and chemoresistance of CC cells by interacting with SEPW1P RNAs 21 . By piRNA expression profile analysis, Bartos et al report that piRNA-9491 and piRNA-12488 were significantly dysregulated in glioblastoma cells and could reduce the ability to form colonies in vitro 17 .…”

PIWIL1 gene polymorphism and pediatric acute lymphoblastic leukemia relapse susceptibility among Chinese children: a five-center case–control study

“…PIWIL1 inhibits the invasion and migration abilities of pancreatic stellate cells through the PI3K/AKT/mTOR signaling pathway (21). It also appears to be involved in the carcinogenesis of pancreatic cancer (22). Knockdown of PIWIL1 could inhibit cell proliferation and induce apoptosis in glioma cells (23).…”

Liquid Biopsy and Cancer: An Ongoing Story

“…A novel piRNA, known as piR-162725 , was recently identified in pancreatic cancer patients by liquid biopsy. Interestingly, the potential of the serum carbohydrate antigen 19-9 (CA19-9) biomarker to identify pancreatic cancer patients was greatly enhanced when combined with piR-162725 detection [ 15 ]. Given that alterations in DNA or in different RNA species could not reveal what happened in proteins, proteome profiling in liquid biopsy samples may provide clinically relevant information throughout all stages of cancer progression.…”