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SLPI (secreted leukocyte protease inhibitor) has recently emerged as a promising biomarker in breast cancer, with several independent studies demonstrating its association with aggressive disease. The initial study employed a xenograft model of human breast cancer metastasis and identified SLPI as one of three markers that correlated with decreased survival and increased lymph node involvement (PMID:15994930). In this model, differential expression between poorly metastatic and highly metastatic variants underscored the potential utility of SLPI in prognostication.
Subsequent multi-patient investigations further reinforced the link between SLPI expression and breast cancer outcome. In one study, gene expression profiling of archival breast cancer tissues revealed that elevated SLPI expression was significantly associated with both disease-free and overall survival in a cohort comprising 30 relapse cases versus 30 non‐relapse cases, with additional validation in a set of 127 tumors (PMID:18561318). This evaluation highlights the reproducibility of SLPI as a marker in diverse patient populations.
Genetic evidence, as captured through comparative gene expression analysis, supports the notion that SLPI upregulation is a common feature among tumors with clinically aggressive behavior. Although no specific pathogenic coding variant was reported in these studies, the consistent overexpression across independent datasets serves as surrogate genetic evidence. The observations were generated by robust methodologies including microarray analysis and quantitative RT‑PCR, providing moderate genetic evidence for the role of SLPI in breast cancer progression.
Functional studies add further weight to the association by demonstrating that elevated SLPI levels can mediate biological processes contributing to metastasis. In the xenograft model, increased SLPI expression appeared to drive enhanced tumor invasiveness and survival, a finding that aligns with tissue array analyses where high SLPI expression correlated with lymph node metastasis. The convergence of these experimental findings with clinical correlations provides a moderate level of functional evidence supporting this gene–disease relationship.
While the experimental evidence from functional assessments in cystic fibrosis (which involved engineered SLPI variants) provides insights into the protein’s stability and anti‐inflammatory properties, the direct translational relevance to breast cancer is supported by the independent clinical observations. No conflicting evidence has been reported regarding SLPI’s prognostic role in breast cancer. In aggregate, the genetic and functional data coalesce into a strong association between SLPI and breast cancer as a prognostic marker.
Key take‑home: Integration of multi‑cohort gene expression data with functional xenograft studies demonstrates that SLPI is a robust prognostic biomarker in breast cancer, underscoring its potential utility in diagnostic decision‑making, commercial assay development, and future publication efforts.
Gene–Disease AssociationStrongTwo independent studies, including a xenograft assay (PMID:15994930) and a gene expression analysis of 60 to 127 cases (PMID:18561318), demonstrate significant correlations between SLPI expression and aggressive breast cancer features. Genetic EvidenceModerateRobust gene expression analyses across multiple cohorts consistently demonstrate SLPI upregulation in aggressive breast cancer, despite the absence of discrete pathogenic coding variants. Functional EvidenceModerateFunctional assays using a xenograft model and tissue microarrays show that high SLPI levels promote metastatic potential and correlate with poor clinical outcomes, supporting its role in disease progression. |