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Preprint WatchMildSeptember 26th, 2026

KLK5 overexpression predicts poor prognosis and promotes migration and adhesion in non-small cell lung cancer

Stuardo-Parada A, Figueroa CD, Turones L, Robles CM, Bascur P, Pavicic F, Torres-Farfán C, López R, Villarroel-Espindola F, Dreyer T, Magdolen V, Ehrenfeld P.

KLK5 overexpression in A549 lung adenocarcinoma cells increases migration and matrix adhesion and associates with shorter overall and progression-free survival, proposing KLK5 as a prognostic biomarker and candidate target in NSCLC.

Mild contradiction

1 prior failure

One documented clinical failure (Phase 1 or 2) overlaps with the claimed mechanism.

This preprint proposes KLK5 as a driver of migration and adhesion in non-small cell lung cancer, based on Kaplan-Meier Plotter survival associations and A549 overexpression experiments. Claidex holds one prior KLK5 failure, ds2325a-klk5-netherton-syndrome-business-decision, in which the DS-2325a Phase 1/2 program in Netherton syndrome ended on a business decision. The indications do not overlap and the modalities differ, so the prior record is context rather than contradiction. The relevant caution is that the preprint's evidence is correlative survival data plus a single cell line, which is the level of support that has repeatedly failed to survive translation, and that a clinical KLK5 inhibitor already reached the clinic and was dropped for non-scientific reasons. Severity is MILD because the single matching claim is a sponsor decision rather than an efficacy failure.

Abstract excerpt

Background Kallikrein-related peptidase 5 (KLK5) is a secreted serine protease involved in extracellular matrix remodeling and proteolytic signaling, but its role in non-small cell lung cancer (NSCLC) remains poorly understood. Methods The association between KLK5 expression and patient survival was first evaluated in silico in publicly available NSCLC datasets using the Kaplan–Meier Plotter platform, stratified by overall and progression-free survival and by histological subtype. Functional effects were then examined in vitro in the lung adenocarcinoma cell line A549, using stable KLK5-overexpressing clones, an empty-vector control, and stimulation with exogenous recombinant KLK5 (rKLK5). Migration was assessed by Transwell assays, adhesion to extracellular matrix components (including collagen I and fibronectin) by adhesion assays, and proliferation and cisplatin sensitivity by cell viability assays. Epithelial–mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, and vimentin) and the effect of cisplatin on KLK5 expression were evaluated by quantitative PCR, ELISA, Western blot, and immunofluorescence. Results High KLK5 expression was significantly associated with shorter overall and progression-free survival, particularly in lung adenocarcinoma, supporting its potential value as a prognostic biomarker. In A549 cells, both KLK5 overexpression and exogenous recombinan

Matching Claidex post-mortems

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This is an automated contradiction flag, not an editorial judgment on the preprint's quality. Flags identify where the preclinical literature and the clinical failure record diverge.