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Ramos-Triguero, AnnaAuthor
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Overexpression of KMT9α Is Associated with Aggressive Basal-like Muscle-Invasive Bladder Cancer

Publicated to:Cells. 12 (4): 589- - 2023-02-01 12(4), DOI: 10.3390/cells12040589

Authors: Koll, Florestan J; Metzger, Eric; Hamann, Jana; Ramos-Triguero, Anna; Bankov, Katrin; Koellermann, Jens; Doering, Claudia; Chune, Felix K H; Schuele, Roland; Wild, Peter J; Reis, Henning

Affiliations

Deutsch Konsortium Translationale Krebsforschung D, D-79106 Freiburg, Germany - Author
Frankfurt Inst Adv Studies, D-60438 Frankfurt, Germany - Author
Univ Canc Ctr UCT Frankfurt, Univ Hosp, Goethe Univ, Theodor Stern Kai 7, D-60590 Frankfurt, Germany - Author
Univ Freiburg, Klinikum Albert Ludwigs, Klin Urol & Zentrale Klin Forsch, D-79106 Freiburg, Germany - Author
Univ Hosp Frankfurt, Dr Senckenberg Inst Pathol, D-60590 Frankfurt, Germany - Author
Univ Hosp Frankfurt, Goethe Univ, Dept Urol, Theodor Stern Kai 7, D-60590 Frankfurt, Germany - Author
Univ Hosp, Goethe Univ, Frankfurt Canc Inst FCI, Theodor Stern Kai 7, D-60590 Frankfurt, Germany - Author
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Abstract

Muscle-invasive bladder cancer (MIBC) is associated with limited response rates to systemic therapy leading to a significant risk of recurrence and death. A recently discovered histone methyltransferase KMT9, acts as an epigenetic regulator of carcinogenesis in different tumor entities. In this study, we investigated the presence and association of histological and molecular subtypes and their impact on the survival of KMT9 alpha in MIBC. We performed an immunohistochemical (IHC) analysis of KMT9 alpha in 135 MIBC patients undergoing radical cystectomy. KMT9 alpha was significantly overexpressed in the nucleus in MIBC compared to normal urothelium and low-grade urothelial cancer. Using the HTG transcriptome panel, we assessed mRNA expression profiles to determine molecular subtypes and identify differentially expressed genes. Patients with higher nuclear and nucleolar KMT9 alpha expression showed basal/squamous urothelial cancer characteristics confirmed by IHC and differentially upregulated KRT14 expression. We identified a subset of patients with nucleolar expression of KMT9 alpha, which was associated with an increased risk of death in uni- and multivariate analyses (HR 2.28, 95%CI 1.28-4.03, p = 0.005). In conclusion, basal-like MIBC and the squamous histological subtype are associated with high nuclear KMT9 alpha expression. The association with poor survival makes it a potential target for the treatment of bladder cancer.

Keywords
ChemotherapyHistoneHistone methyltransferaseLanguageMibcMolecular subtypeMolecular subtypesMulticenterNivolumabP53TherapUrothelial carcinoma

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Cells 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, 2023, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Biochemistry, Genetics and Molecular Biology (Miscellaneous).

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: 5.1, 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 May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-09, the following number of citations:

  • WoS: 3
  • Scopus: 5
  • OpenCitations: 7
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 2025-05-09:

  • 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: 8.
  • 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: 8 (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.
  • 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: Germany.