An Expression-Based Site of Origin Diagnostic Method Designed for Clinical Application to Cancer of Unknown Origin
Open Access
- 15 May 2005
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 65 (10), 4031-4040
- https://doi.org/10.1158/0008-5472.can-04-3617
Abstract
Gene expression profiling offers a promising new technique for the diagnosis and prognosis of cancer. We have applied this technology to build a clinically robust site of origin classifier with the ultimate aim of applying it to determine the origin of cancer of unknown primary (CUP). A single cDNA microarray platform was used to profile 229 primary and metastatic tumors representing 14 tumor types and multiple histologic subtypes. This data set was subsequently used for training and validation of a support vector machine (SVM) classifier, demonstrating 89% accuracy using a 13-class model. Further, we show the translation of a five-class classifier to a quantitative PCR–based platform. Selecting 79 optimal gene markers, we generated a quantitative-PCR low-density array, allowing the assay of both fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissue. Data generated using both quantitative PCR and microarray were subsequently used to train and validate a cross-platform SVM model with high prediction accuracy. Finally, we applied our SVM classifiers to 13 cases of CUP. We show that the microarray SVM classifier was capable of making high confidence predictions in 11 of 13 cases. These predictions were supported by comprehensive review of the patients' clinical histories.Other Versions
This publication has 45 references indexed in Scilit:
- Diagnostic strategies for unknown primary cancerCancer, 2004
- Measurement of Gene Expression in Archival Paraffin-Embedded Tissues: Development and Performance of a 92-Gene Reverse Transcriptase-Polymerase Chain Reaction AssayThe American Journal of Pathology, 2004
- Accurate Molecular Classification of Human Cancers Based on Gene Expression Using a Simple Classifier with a Pathological Tree-Based FrameworkThe American Journal of Pathology, 2003
- Primary and Metastatic Mucinous Adenocarcinomas in the OvariesThe American Journal of Surgical Pathology, 2003
- Towards Quantitative mRNA Analysis in Paraffin-Embedded Tissues Using Real-Time Reverse Transcriptase-Polymerase Chain Reaction: A Methodological Study on Lymph Nodes from Melanoma PatientsThe Journal of Molecular Diagnostics, 2003
- Organ-Specific Molecular Classification of Primary Lung, Colon, and Ovarian Adenocarcinomas Using Gene Expression ProfilesThe American Journal of Pathology, 2001
- Identification of genes differentially over-expressed in lung squamous cell carcinoma using combination of cDNA subtraction and microarray analysisOncogene, 2000
- Systematic variation in gene expression patterns in human cancer cell linesNature Genetics, 2000
- Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancerThe Lancet, 1998
- Early metastatic cancer of unknown primary origin at presentation. A clinical study of 302 consecutive autopsied patientsArchives of Internal Medicine, 1988