Meta-Analysis of Gene Expressions in Testicular Germ Cell Tumor Histologies.

Finn Edler Von Eyben,Jorge Parraga-Alava

doi:10.3390/ijms21124487

Abstract

There is no consensus as to how a precursor lesion, germ cell neoplasia in situ (GCNIS), develops into the histologic types of testicular germ cell tumor type II (TGCT). The present meta-analysis examined RNA expressions of 24 candidate genes in three datasets. They included 203 samples of normal testis (NT) and histologic types of TGCT. The Fisher’s test for combined p values was used for meta-analysis of the RNA expressions in the three datasets. The histologic types differed in RNA expression of PRAME, KIT, SOX17, NANOG, KLF4, POU5F1, RB1, DNMT3B, and LIN28A (p < 0.01). The histologic types had concordant differences in RNA expression of the genes in the three datasets. Eight genes had overlap with a high RNA expression in at least two histologic types. In contrast, only seminoma (SE) had a high RNA expression of KLF4 and only embryonal carcinoma (EC) had a high RNA expression of DNMT3B. In conclusion, the meta-analysis showed that the development of the histologic types of TGCT was driven by changes in RNA expression of candidate genes. According to the RNA expressions of the ten genes, TGCT develops from NT over GCNIS, SE, EC, to the differentiated types of TGCT.

Highlights

Testicular germ cell tumor type II (TGCT) is the most frequent malignancy in young adult men
To further study how TGCT develops, we aimed to investigate whether the histologic types of TGCT differed significantly in RNA expression of candidate genes
Our meta-analysis examined RNA expression of 24 candidate genes in three datasets of TGCT

Summary

Introduction

Testicular germ cell tumor type II (TGCT) is the most frequent malignancy in young adult men. Oncologists follow the TNM (T for primary tumor, N for regional lymph node metastases, M for distant metastases) classification that separates TGCT into seminoma and nonseminomatous germ cell tumors (NSGCT) [1]. The WHO classification of tumors of the urogenital system and male genital organs 2016 [2] acknowledges that TGCT develops from a common precursor lesion, germ cell neoplasia in situ (GCNIS). The research started in 1896, in which Wilms reported that TGCT was derived from normal testicular germ cells [3]. In 1959, Teilum described a separate histologic type of NSGCT, YST ( called endodermal sinus tumor) [5]. In 1990, de Jong summarized studies that showed TGCT had a characteristic isochromosome of the short arm of chromosome 12, 12p, and i(12p) [6]

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