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Grant support

This research was funded by the "5th Beca Carmen Delgado/Miguel Perez-Mateo de AESPANC-ACANPAN (ref: 25791/001)" and by the Spanish Health Institute Carlos III (ISCIII-FEDER), grant number PI19/01231.

Analysis of institutional authors

Garcia-Jimenez, CustodiaAuthorMartinez-Useros, JavierCorresponding Author

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January 16, 2023
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Article

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

Publicated to:Journal Of Clinical Medicine. 11 (24): 7310- - 2022-12-01 11(24), DOI: 10.3390/jcm11247310

Authors: Li, Weiyao; Gonzalez-Gonzalez, Miguel; Sanz-Criado, Lara; Garcia-Carbonero, Nuria; Celdran, Angel; Villarejo-Campos, Pedro; Minguez, Pablo; Pazo-Cid, Roberto; Garcia-Jimenez, Custodia; Orta-Ruiz, Alberto; Garcia-Foncillas, Jesus; Martinez-Useros, Javier

Affiliations

Clin San Carlos Univ Hosp, Microbiol Lab, Madrid 28040, Spain - Author
Fdn Jimenez Diaz Univ Hosp, Gen & Hepatobiliary Surg Unit, Madrid 28040, Spain - Author
Hosp Univ Miguel Servet, Dept Med Oncol, Zaragoza 50009, Spain - Author
Inst Invest Sanitaria Hosp Clin San Carlos IdISSC, Hosp Clin San Carlos, Dept Med Oncol, CIBERONC, Madrid 28040, Spain - Author
MD Anderson Canc Ctr Madrid, Dept Med Oncol, Madrid 28033, Spain - Author
Rey Juan Carlos Univ, Area Physiol, Dept Basic Hlth Sci, Fac Hlth Sci, Madrid 28922, Spain - Author
Sun Yat sen Univ, Affiliated Hosp 6, Dept Gastrointestinal Surg, Guangzhou 510085, Peoples R China - Author
UAM, Genet & Genom Dept, IIS Fdn Jimenez Diaz, Univ Autonoma Madrid IIS FJD,Ctr Biomed Network Re, Madrid 28040, Spain - Author
UAM, Translat Oncol Div, OncoHlth Inst, Hlth Res Inst Fdn Jimenez Diaz,Fdn Jimenez Diaz Un, Madrid 28040, Spain - Author
Univ Francisco de Vitoria, Fac Expt Sci, Pozuelo De Alarcon 28223, Spain - Author
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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.

Keywords

AdenocarcinomaArticleBiological markerBlood samplingCa 19-9 antigenCa19-9Cancer stagingCancer susceptibilityChemotherapyClinical articleCohort analysisControlled studyDiagnosisDown regulationEmerging rolesGemcitabineGene expressionHigh throughput sequencingHumanHuman cellHuman tissueImmunocytochemistryIntraductal papillary mucinous tumorLiquid biopsyMapk pathwayMapk signalingOverall survivalPancreas cancerPancreatic cancerPancreatic cancer cell linePancrelipasePir-823PirnaPiwi interacting rnaPiwi proteinPiwi protein piwil3Piwi protein piwil4Piwi proteinsPiwil3Piwil4Preoperative ca-19-9Progression free survivalProportional hazards modelRna sequencingSmall non-coding rnaSmall rnaSmall untranslated rnaStatisticsSurvival rateUnclassified drug

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of Clinical Medicine due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine (Miscellaneous).

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 2.05. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 1.67 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 7.2 (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-25, the following number of citations:

  • WoS: 15
  • Scopus: 15
  • Europe PMC: 10

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-25:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 21.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 26 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 0.5.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: China.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: Last Author (Martínez Useros, Javier).

the author responsible for correspondence tasks has been Martínez Useros, Javier.