Evidence map›Paper›PMID 33260070›Full record

ArticleTranslational oncology2021

Relative expression of KLK5 to LEKTI is associated with aggressiveness of oral squamous cell carcinoma.

Márcia Gaião Alves, Márcio Hideki Kodama, Elaine Zayas Marcelino da Silva, Bruno Belmonte Martinelli Gomes, Rodrigo Alberto Alves da Silva, Gabriel Viliod Vieira, Vani Maria Alves, Carol Kobori da Fonseca, Ana Carolina Santana, Nerry Tatiana Cecílio and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.5field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 20 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 2 institutions in 2 countries.

Márcia Gaião AlvesDepartment of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
Márcio Hideki KodamaDepartment of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
Elaine Zayas Marcelino da SilvaDepartment of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil; Proteases and Tissue Remodeling Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Bruno Belmonte Martinelli GomesDepartment of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
Rodrigo Alberto Alves da SilvaDepartment of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
Gabriel Viliod VieiraDepartment of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
Vani Maria AlvesDepartment of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
Carol Kobori da FonsecaDepartment of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
Ana Carolina SantanaDepartment of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
Nerry Tatiana CecílioDepartment of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
Mara Silvia Alexandre CostaDepartment of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
Maria Célia JamurDepartment of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
Constance OliverDepartment of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
Thiago Mattar CunhaDepartment of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
Thomas H BuggeProteases and Tissue Remodeling Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Paulo Henrique Braz-SilvaDepartment of Stomatology, School of Dentistry, University of Sao Paulo, Sao Paulo, SP - Brazil; Laboratory of Virology, Institute of Tropical Medicine of Sao Paulo, School of Medicine, University of Sao Paulo, Sao Paulo, SP - Brazil.
Leandro M ColliDepartment of Image Science, Hematology and Medical Oncology, Ribeirao Preto Medical School, University of Sao Paulo, SP - Brazil.
Katiuchia Uzzun SalesDepartment of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil. Electronic address: salesk@fmrp.usp.br.
Universidade de São Paulo · BRNational Institutes of Health · US

Funding

Cell surface serine proteases in development, tissue repair, and malignancyZIADE000699 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI BUGGE, THOMAS H · 2009 to 2025
$34.1M
6 · The paper itself

Abstract

backgroundOral squamous cell carcinoma (OSCC) remains a challenging cancer to treat despite all the advances of the last 50 years. Kallikrein 5 (KLK5) is among the serine proteases implicated in OSCC development. However, whether the activity of KLK5 promotes carcinogenesis is still controversial. Moreover, knowledge regarding the role of the KLK5 cognate inhibitor, Lympho-Epithelial Kazal-Type related Inhibitor (LEKTI), in OSCC is scarce. We have, thus, sought to investigate the importance of KLK5 and LEKTI expression in premalignant and malignant lesions of the oral cavity.

methodsKLK5 and LEKTI protein expression was evaluated in 301 human samples, which were comprised of non-malignant and malignant lesions of the oral cavity. Moreover, a bioinformatic analysis of the overall survival rate from 517 head and neck squamous cell carcinoma (HNSCC) samples was performed. Additionally, to mimic the uncovered KLK5 to serine peptidase inhibitor (SPINK5) imbalance, the KLK5 gene was abrogated in an OSCC cell line using CRISPR-Cas9 technology. The generated cell line was then used for in vivo and in vitro carcinogenesis related experiments.

resultsLEKTI was found to be statistically downregulated in OSCCs, with increased KLK5/SPINK5 mRNA ratio being associated with a shorter overall survival (p = 0.091). Indeed, disruption of KLK5 to SPINK5 balance through the generation of KLK5 null OSCC cells led to smaller xenografted tumors and statistically decreased proliferation rates following multiple time points of BrdU treatment in vitro.

conclusionThe association of increased enzyme/inhibitor ratio with poor prognosis indicates KLK5 to SPINK5 relative expression as an important prognostic marker in OSCC.

Indexed as

Kallikrein 5LEKTIbOSCCPrognostic markerSPINK5

Identifiers

PMID33260070
PMCPMC7708696
OpenAlexW3109674246

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.