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PiRNA Obtained through Liquid Biopsy as a Possible Cancer Biomarker.

ABSTRACT: In recent years PIWI-interacting RNAs (piRNAs) have gained the interest of scientists, mainly because of their possible implications in cancer. Many kinds of research showed how their expression can be linked to malignant diseases. However, most of them evaluated the expression of piRNAs in tumor tissues. It was shown how these non-coding RNAs can interfere with many signaling pathways involved in the regulation of proliferation or apoptosis. A comparison of piRNA expression in tumor tissue and adjacent healthy tissues has demonstrated they can be used as biomarkers. However, this way of obtaining samples has a significant drawback, which is the invasiveness of such a procedure. Liquid biopsy is an alternative for acquiring biological material with little to no harm to a patient. Several different piRNAs in various types of cancer were shown to be expressed in bodily fluids such as blood or urine. Furthermore, their expression significantly differed between cancer patients and healthy individuals. Hence, this review aimed to assess the possible use of liquid biopsy for cancer diagnosis with piRNAs as biomarkers.

SUBMITTER: Limanowka P

PROVIDER: S-EPMC10252662 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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PiRNA Obtained through Liquid Biopsy as a Possible Cancer Biomarker.

Limanówka Piotr P Ochman Błażej B Świętochowska Elżbieta E

Diagnostics (Basel, Switzerland) 20230529 11

In recent years PIWI-interacting RNAs (piRNAs) have gained the interest of scientists, mainly because of their possible implications in cancer. Many kinds of research showed how their expression can be linked to malignant diseases. However, most of them evaluated the expression of piRNAs in tumor tissues. It was shown how these non-coding RNAs can interfere with many signaling pathways involved in the regulation of proliferation or apoptosis. A comparison of piRNA expression in tumor tissue and ...[more]

PMID: 37296747

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Project description: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.

Project description:BackgroundUveal melanoma (UM) is the most common intraocular tumor in adults. Despite good primary tumor control, up to 50% of patients develop metastasis, which is lethal. UM often presents asymptomatically and is usually diagnosed by clinical examination and imaging, making it one of the few cancer types diagnosed without a biopsy. Hence, alternative diagnostic tools are needed. Circulating tumor DNA (ctDNA) has shown potential as a liquid biopsy target for cancer screening and monitoring. The aim of this study was to evaluate the feasibility and clinical utility of ctDNA detection in UM using specific UM gene mutations.MethodsWe used the highly sensitive digital droplet PCR (ddPCR) assay to quantify UM driver mutations (GNAQ, GNA11, PLCβ4 and CYSTLR2) in cell-free DNA (cfDNA). cfDNA was analyzed in six well established human UM cell lines with known mutational status. cfDNA was analyzed in the blood and aqueous humor of an UM rabbit model and in the blood of patients. Rabbits were inoculated with human UM cells into the suprachoroidal space, and mutated ctDNA was quantified from longitudinal peripheral blood and aqueous humor draws. Blood clinical specimens were obtained from primary UM patients (n = 14), patients presenting with choroidal nevi (n = 16) and healthy individuals (n = 15).ResultsThe in vitro model validated the specificity and accuracy of ddPCR to detect mutated cfDNA from UM cell supernatant. In the rabbit model, plasma and aqueous humor levels of ctDNA correlated with tumor growth. Notably, the detection of ctDNA preceded clinical detection of the intraocular tumor. In human specimens, while we did not detect any trace of ctDNA in healthy controls, we detected ctDNA in all UM patients. We observed that UM patients had significantly higher levels of ctDNA than patients with nevi, with a strong correlation between ctDNA levels and malignancy. Noteworthy, in patients with nevi, the levels of ctDNA highly correlated with the presence of clinical risk factors.ConclusionsWe report, for the first time, compelling evidence from in vitro assays, and in vivo animal model and clinical specimens for the potential of mutated ctDNA as a biomarker of UM progression. These findings pave the way towards the implementation of a liquid biopsy to detect and monitor UM tumors.

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PiRNA Obtained through Liquid Biopsy as a Possible Cancer Biomarker.

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PiRNA Obtained through Liquid Biopsy as a Possible Cancer Biomarker.

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