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Molecular Characterization of Neuroendocrine-like Bladder Cancer
- Source :
- Clinical Cancer Research, 25(13), 3908-3920. American Association for Cancer Research Inc.
- Publication Year :
- 2019
-
Abstract
- Purpose: Neuroendocrine (NE) bladder carcinoma is a rare and aggressive variant. Molecular subtyping studies have found that 5% to 15% of muscle-invasive bladder cancer (MIBC) have transcriptomic patterns consistent with NE bladder cancer in the absence of NE histology. The clinical implications of this NE-like subtype have not been explored in depth. Experimental Design: Transcriptome-wide expression profiles were generated for MIBC collected from 7 institutions and clinical-use of Decipher Bladder. Using unsupervised clustering, we generated a clustering solution on a prospective training cohort (PTC; n = 175), developed single-sample classifiers to predict NE tumors, and evaluated the resultant models on a testing radical cystectomy (RC) cohort (n = 225). A random forest model was finalized and applied to 5 validation cohorts (n = 1302). Uni- and multivariable survival analyses were used to characterize clinical outcomes. Results: In the training cohort (PTC), hierarchical clustering using an 84-gene panel showed a cluster of 8 patients (4.6%) with highly heterogeneous expression of NE markers in the absence of basal or luminal marker expression. NE-like tumors were identified in 1% to 6.6% of cases in validation cohorts. Patients with NE-like tumors had significantly worse 1-year progression-free survival (65% NE-like vs. 82% overall; P = 0.046) and, after adjusting for clinical and pathologic factors, had a 6.4-fold increased risk of all-cause mortality (P = 0.001). IHC confirmed the neuronal character of these tumors. Conclusions: A single-patient classifier was developed that identifies patients with histologic urothelial cancer harboring a NE transcriptomic profile. These tumors represent a high-risk subgroup of MIBC, which may require different treatment.
- Subjects :
- 0301 basic medicine
Oncology
Male
Cancer Research
medicine.medical_specialty
medicine.medical_treatment
Cystectomy
03 medical and health sciences
0302 clinical medicine
SDG 3 - Good Health and Well-being
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
Carcinoma
Biomarkers, Tumor
Medicine
Humans
Progression-free survival
Neoplasm Metastasis
610 Medicine & health
Pathological
Aged
Neoplasm Staging
Aged, 80 and over
Bladder cancer
business.industry
Gene Expression Profiling
Computational Biology
Reproducibility of Results
Histology
Middle Aged
medicine.disease
Prognosis
Immunohistochemistry
Carcinoma, Neuroendocrine
030104 developmental biology
Treatment Outcome
Urinary Bladder Neoplasms
030220 oncology & carcinogenesis
Cohort
Female
business
Transcriptome
Subjects
Details
- ISSN :
- 10780432
- Volume :
- 25
- Issue :
- 13
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....f5f0906242ca261db98f010d3fdc1661