Title :
Biomarker development for pancreatic ductal adenocarcinoma using integrated analysis of mRNA and miRNA expression
Author :
Min-Seok Kwon ; Yongkang Kim ; Seungyeoun Lee ; Junghyun Namkung ; Taegyun Yun ; Sung Gon Yi ; Sangjo Han ; Meejoo Kang ; Sun Whe Kim ; Jin-Young Jang ; Taesung Park
Author_Institution :
Interdiscipl. program in Bioinf., Seoul Nat. Univ., Seoul, South Korea
Abstract :
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, which has dismal prognosis because of its silent early symptoms, high metastatic potential, and resistance to conventional therapies. Although a PDAC patient who is diagnosed at an early stage would have a substantial increase in chance of survival, the survival rate is poor because there is no efficient non-invasive diagnostic test in the early stage. In this study, we developed an efficient prediction models to detect PDAC in its early stages. Our prediction models use both mRNA and miRNA expression data from 104 PDAC tissues and 17 normal pancreatic tissues using microarray technology. After quality control, we built prediction models based on support vector machine (SVM) from mRNA and miRNA expressions for detecting early PDAC. To prevent over-fitting effect, we conducted leave-one-out cross validation (LOOCV) and 5-fold cross validation (CV). For independent validation of prediction models, we performed evaluation on independent datasets from Gene Expression Omnibus (GEO). After the validation, we identified 28 single markers and 231 combinations of markers with powerful prediction performance. In addition, the marker candidates are annotated with cancer pathways using gene ontology analysis. Our prediction models for PDAC may have potential for early diagnosis of PDAC.
Keywords :
RNA; bioinformatics; biological organs; biological tissues; biomedical measurement; cancer; lab-on-a-chip; patient diagnosis; support vector machines; 5-fold cross validation; GEO; Gene Expression Omnibus; LOOCV; PDAC detection; PDAC diagnosis; PDAC metastatic potential; PDAC prediction model validation; PDAC symptoms; PDAC theraphy; PDAC tissues; SVM; biomarker development; cancer pathways; conventional therapy; dismal prognosis; gene ontology analysis; leave-one-out cross validation; mRNA expression data; mRNA integrated analysis; miRNA expression data; miRNA integrated analysis; microarray technology; noninvasive diagnostic test; over-fitting effect; pancreatic cancer; pancreatic ductal adenocarcinoma; pancreatic tissues; support vector machine; Barium; Blood; Cancer; Lungs; Ontologies; Predictive models; Reliability; Biomarker development; Pancreatic ductal adenocarcinoma (PDAC); mRNA expression; miRNA expression; prediction model;
Conference_Titel :
Bioinformatics and Biomedicine (BIBM), 2014 IEEE International Conference on
Conference_Location :
Belfast
DOI :
10.1109/BIBM.2014.6999167