Cancer diagnosis marker extraction for soft tissue sarcomas based on gene expression profiling data by using projective adaptive resonance theory (PART) filtering method.
BACKGROUND
Recent advances in genome technologies have provided an excellent opportunity to determine the complete biological characteristics of neoplastic tissues, resulting in improved diagnosis and selection of treatment. To accomplish this objective, it is important to establish a sophisticated algorithm that can deal with large quantities of data such as gene expression profiles obtained by DNA microarray analysis.


RESULTS
Previously, we developed the projective adaptive resonance theory (PART) filtering method as a gene filtering method. This is one of the clustering methods that can select specific genes for each subtype. In this study, we applied the PART filtering method to analyze microarray data that were obtained from soft tissue sarcoma (STS) patients for the extraction of subtype-specific genes. The performance of the filtering method was evaluated by comparison with other widely used methods, such as signal-to-noise, significance analysis of microarrays, and nearest shrunken centroids. In addition, various combinations of filtering and modeling methods were used to extract essential subtype-specific genes. The combination of the PART filtering method and boosting--the PART-BFCS method--showed the highest accuracy. Seven genes among the 15 genes that are frequently selected by this method--MIF, CYFIP2, HSPCB, TIMP3, LDHA, ABR, and RGS3--are known prognostic marker genes for other tumors. These genes are candidate marker genes for the diagnosis of STS. Correlation analysis was performed to extract marker genes that were not selected by PART-BFCS. Sixteen genes among those extracted are also known prognostic marker genes for other tumors, and they could be candidate marker genes for the diagnosis of STS.


CONCLUSIONS
The procedure that consisted of two steps, such as the PART-BFCS and the correlation analysis, was proposed. The results suggest that novel diagnostic and therapeutic targets for STS can be extracted by a procedure that includes the PART filtering method.
Takahashi
Hiro
H
Department of Biotechnology, School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan. hirtakah@gan2.res.ncc.go.jp
Nemoto
Takeshi
T
Yoshida
Teruhiko
T
Honda
Hiroyuki
H
Hasegawa
Tadashi
T
D000465:Algorithms; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D012509:Sarcoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D012983:Soft Tissue Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism
D014408:Biomarkers, Tumor