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Grant support

This work was supported by the following grants: AECC (Spanish association against cancer)-Catalunya 2013 (to Dr. Navarro); SDCSD (body donation service) of University of Barcelona (to Dr. Monzo); and PI12/00405 from Plan Nacional de I+D+I cofinanced by ISCIII-Subdireccion General de Evaluacion and Fondo Europeo de Desarrollo Regional (FEDER), Spanish association of pneumology and thoracic surgery (SEPAR), Catalan Society of Pneumology (SOCAP) (to Dr. Marrades). Mr. Castellano and Ms. Cordeiro are APIF fellows of the University of Barcelona. Mr. Castellano performed the research and wrote the manuscript; Dr. Navarro designed and supervised the research, analyzed the data, and wrote the manuscript; Ms. Cordeiro, Ms. Fuster, and Dr. Munoz performed the research; Drs. Vinolas, Marrades, Moises, and Molins selected cases and analyzed the clinical data; Drs. Ramirez and Saco provided samples and performed histopathological review; and Dr. Monzo supervised the research and approved the final version of the paper. All the authors have seen and approved this final version of the article and agree with the decision to submit it.

Analysis of institutional authors

Ramirez Mahaluf, Juan PabloAuthorMuñoz Santos , CarlosAuthorMunoz Garcia, Carmen MariaAuthorNavarro Ponz, AlfonsAuthorNavarro, ACorresponding AuthorVinolas, NAuthorN//marradesAuthorRm//moisesAuthorA//sacoAuthorMunoz, CAuthorD//molinsAuthorL//ramirezAuthorJ//monzoAuthor

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February 17, 2017
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LincRNA-p21 Impacts Prognosis in Resected Non-Small Cell Lung Cancer Patients through Angiogenesis Regulation

Publicated to:Journal Of Thoracic Oncology. 11 (12): 2173-2182 - 2016-12-01 11(12), DOI: 10.1016/j.jtho.2016.07.015

Authors: Castellano JJ, Navarro A, Viñolas N, Marrades RM, Moises J, Cordeiro A, Saco A, Muñoz C, Fuster D, Molins L, Ramirez J, Monzo M

Affiliations

Department of Medical Oncology, Clinic Institute of Haematological and Oncological Diseases, Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS (August Pi i Sunyer Biomedical Research Institute), Barcelona, Spain - Author
Department of Pathology, The Biomedical Diagnostic Center, Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS (August Pi i Sunyer Biomedical Research Institute), CIBERES, Barcelona, Spain - Author
Department of Pneumology, Thorax Clinic Institute, Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS (August Pi i Sunyer Biomedical Research Institute), CIBER of Respiratory Diseases (CIBERES), Barcelona, Spain - Author
Department of Thoracic Surgery, Thorax Clinic Institute, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain - Author
Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain - Author
Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain - Author
Univ Barcelona, Hosp Clin Barcelona, Thorax Clin Inst, Dept Thorac Surg, Barcelona, Spain - Author
Univ Barcelona, IDIBAPS August Pi & Sunyer Biomed Res Inst, Biomed Diagnost Ctr, Dept Pathol,Hosp Clin Barcelona,CIBERES, Barcelona, Spain - Author
Univ Barcelona, IDIBAPS August Pi & Sunyer Biomed Res Inst, CIBER Resp Dis CIBERES, Dept Pneumol,Thorax Clin Inst,Hosp Clin Barcelona, Barcelona, Spain - Author
Univ Barcelona, IDIBAPS August Pi & Sunyer Biomed Res Inst, Clin Inst Haematol & Oncol Dis, Dept Med Oncol,Hosp Clin Barcelona, Barcelona, Spain - Author
Univ Barcelona, Mol Oncol & Embryol Lab, Human Anat Unit, Sch Med,IDIBAPS, Barcelona, Spain - Author
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Abstract

Long intergenic noncoding RNA-p21 (lincRNA-p21) is a long noncoding RNA transcriptionally activated by tumor protein p53 (TP53) and hypoxia inducible factor 1 alpha subunit (HIF1A). It is involved in the regulation of TP53-dependent apoptosis and the Warburg effect. We have investigated the role of lincRNA-p21 in NSCLC.LincRNA-p21 expression was assessed in tumor and normal tissue from 128 patients with NSCLC and correlated with time to relapse and cancer-specific survival (CSS). H23, H1299, and HCC-44 cell lines were cultured in hypoxic conditions after silencing of lincRNA-p21. The TaqMan human angiogenesis array was used to explore angiogenesis-related gene expression. Levels of the protein vascular endothelial growth factor A were measured by enzyme-linked immunosorbent assay in the cell supernatants. Angiogenic capability was measured by human umbilical vein endothelial cell tube formation assay. Microvascular density in tumor samples was analyzed by immunohistochemistry.LincRNA-p21 was down-regulated in tumor tissue, but no association was observed with TP53 mutational status. High lincRNA-p21 levels were associated with poor CSS in all patients (p = 0.032). When patients were classified according to histological subtypes, the impact of lincRNA-p21 was confined to patients with adenocarcinoma in both time to relapse (p = 0.006) and CSS (p < 0.001). To explain the poor outcome of patients with high lincRNA-p21 expression, we studied the role of lincRNA-p21 in angiogenesis in vitro and observed a global downregulation in the expression of angiogenesis-related genes when lincRNA-p21 was inhibited. Moreover, supernatants from lincRNA-p21-inhibited cells were significantly less angiogenic and had lower levels of secreted vascular endothelial growth factor A than controls did. Finally, tumor samples with high lincRNA-p21 levels had higher microvascular density.Our findings suggest that lincRNA-p21 affects outcome in patients with NSCLC adenocarcinoma through the regulation of angiogenesis.Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Keywords

angiogenesisapoptosisendothelial-cellsexpressionhypoxiail-12innatelincrna-p21lncrnaslong non coding rnaslong noncoding rnasmediatornsclcstatisticsvegfAdultAgedAged, 80 and overAngiogenesisApoptosisBiomarkersCarcinomaCarcinoma, non-small-cell lungCell line, tumorEndothelial-cellsExpressionFemaleGene expression profilingHumansHypoxiaLincrna-p21LncrnasLong non coding rnasLong noncoding rnaLong noncoding rnasLung neoplasmsMaleMediatorMetastasisMiddle agedNsclcPrognosisProto-oncogene proteins p21(ras)Rna, long noncodingStatisticsTransfection

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of Thoracic Oncology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2016, it was in position 23/217, thus managing to position itself as a Q1 (Primer Cuartil), in the category Oncology.

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. 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: 2 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 14.13 (source consulted: Dimensions Aug 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-08-02, the following number of citations:

  • WoS: 70
  • Scopus: 56
  • Europe PMC: 52

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 2025-08-02:

  • 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: 40.
  • 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: 43 (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: 1.6.
  • The number of mentions on the social network X (formerly Twitter): 3 (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

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

the author responsible for correspondence tasks has been Navarro López, Alba.