Cellular Relationships of Testicular Germ Cell Tumors Determined by Partial Canonical Correlation Analysis of Gene Expression Signatures

Tingting      Yu; Akiko      Toshimori; Xia      Jinrong; Shigeru      Saito; Xingrong      Zhou; Katsuhisa      Horimoto; Zhining      Fan; Kunio      Shimizu; Huarong      Zhou

Abstract

We designed a procedure to explore cellular relationships from sets of characteristic genes in distinctive cell types, by using a partial canonical correlation analysis. The present procedure was then applied to the characteristic gene sets of seven subtypes of testicular germ cell tumors, reported previously. The cellular relationships were reconstructed well, and were consistent with the general histologic lineage model. New implications for the subtype differentiation were found. In particular, the correspondence between the inferred relationships and the functional characterizations of constituent genes suggested a hypothesis for the classification between seminoma and embryonal carcinoma. The partial canonical correlation analysis is also appropriate for revealing new features of cellular relationships, based on the transcriptional programs. Thus, the present procedure facilitates the creation of a macroscopic view of the cellular relationships, by following the detection of characteristically expressed genes.

Keywords: Cellular relationship, gene expression, graphical model, histologic lineage model, partial canonical correlation analysis, testicular germ cell tumors, Lineage Model, Germ Cell Tumorigenesis, Functional Interpretation, intratubular germ cell neoplasia