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Analysis of institutional authors

Marin Menendez, AlejandroAuthorMarín-Aguilera, MAuthorMunoz, JAuthorCastellvi-Bel, SAuthorCastells, AAuthorGascon, PAuthorMaurel, JCorresponding Author

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May 5, 2014
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Co-expression of matrix metalloproteinase-7 (MMP-7) and phosphorylated insulin growth factor receptor I (pIGF-1R) correlates with poor prognosis in patients with wild-type KRAS treated with cetuximab or panitumumab A GEMCAD study

Publicated to:Cancer Biology & Therapy. 11 (2): 177-183 - 2011-01-15 11(2), DOI: 10.4161/cbt.11.2.13839

Authors: Hoerndler, Carlos; Gallego, Rosa; Garcia-Albeniz, Xabier; Alonso-Espinaco, Virginia; Alonso, Vicente; Escudero, Pilar; Jimeno, Mireya; Ortego, Javier; Codony-Servat, Jordi; Fernandez-Martos, Carlos; Calatrava, Ana; Marin-Aguilera, Mercedes; Munoz, Jenifer; Castellvi-Bel, Sergi; Castells, Antoni; Rubini, Michele; Gascon, Pere; Maurel, Joan

Affiliations

Hosp Clin Zaragoza, Dept Med Oncol, Zaragoza, Spain - Author
Hosp Clin Zaragoza, Dept Pathol, Zaragoza, Spain - Author
Hosp Miguel Servet, Dept Med Oncol, Zaragoza, Spain - Author
Hosp Miguel Servet, Dept Pathol, Zaragoza, Spain - Author
Hospital Miguel Servet - Author
IVO, Dept Med Oncol, Valencia, Spain - Author
IVO, Dept Pathol, Valencia, Spain - Author
Univ Barcelona, Hosp Clin Barcelona, IDIBAPS, CIBEREHD,Dept Gastroenterol, Barcelona, Spain - Author
Univ Barcelona, Hosp Clin Barcelona, IDIBAPS, CIBEREHD,Dept Med Oncol, Barcelona, Spain - Author
Univ Barcelona, Hosp Clin Barcelona, IDIBAPS, CIBEREHD,Dept Pathol, Barcelona, Spain - Author
Univ Ferrara, Med Genet Unit, I-44100 Ferrara, Italy - Author
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Abstract

By transactivacion, phosphorylated insulin growth factor receptor I (IGF-1R) can activate epidermal growth factor receptor (EGFR). MMP-7, produced by colorectal cancer cells, also can activate IGF-1R by degrading IGFBP-3 and releasing IGF-I.A cohort of patients (pts) with advanced colorectal cancer (CRC), under second- or third-line treatment with cetuximab or panitumumab, was tested using immunohistochemistry for expression of the activated form of IGF-1R (p-IGF-1R) and MMP-7. KRAS and BRAF mutation status was determined by sequencing and allelic discrimination analysis, respectively. Analyses were performed in primary CRC tumor samples or metastases, and the association of immunohistochemistry findings, mutational results, and treatment outcomes was investigated in both univariate and multivariate analyses.Expression of activated IGF-1R and MMP-7 was observed in 51 and 49% of pts, respectively. Co-expression of MMP-7 and pIGF-1R (double positivity, DP) was observed in 28 pts (25%). There was no association between KRAS or BRAF mutational status and DP (p=0.52). Pts with DP responded more poorly to first-line chemotherapy (p=0.005) and to anti-EGFR treatment (p=0.01) than non-DP pts. In wild type (WT) KRAS pts, those with DP have poorer PFS (2.7 months vs. 3.5m, p=0.036; HR 1.98, 95% CI 1.05-3.75) and OS (6.4 months vs. 8.6 m, p=0.010; HR 2.33, 95%CI 1.23-4.43) in the adjusted multivariate analysis.Our study suggests that concomitant expression of MMP-7 and activation of p-IGF-1R (DP) correlates with poor prognosis in WT KRAS pts treated with anti-EGFR.

Keywords

activationcetuximabcolorectal cancerexpressionfluorouraciligf-irinsulin growth factoririnotecankras statuspanitumumabprognostic factorsproteinase activitysystemtargettransactivationActivationAdultAgedAged, 80 and overAntibodies, monoclonalAntibodies, monoclonal, humanizedAntineoplastic agentsBraf protein, humanCetuximabCohort studiesColorectal cancerColorectal neoplasmsColorectal-cancerComplicationsDisease-free survivalErbb receptorsExpressionFemaleHumansInsulin growth factorInsulin-like growth factor binding protein 3Insulin-like growth factor iKras protein, humanKras statusMaleMatrilysinMatrix metalloproteinase 7Middle agedPanitumumabPhosphorylationPrognostic factorsProto-oncogene proteinsProto-oncogene proteins b-rafProto-oncogene proteins p21(ras)Ras proteinsReceptor, igf type 1TrialTyrosine kinase

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Cancer Biology & Therapy 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, 2011, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Pharmacology.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 1.15, which 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: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-04, the following number of citations:

  • WoS: 9
  • Scopus: 9
  • Europe PMC: 6
  • Google Scholar: 16

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 2025-07-04:

  • 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: 41 (PlumX).

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: AUSTIN; Italy.

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 (Maurel Santasusana, Joan).

the author responsible for correspondence tasks has been Maurel Santasusana, Joan.