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

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.

Teratoma Growth Retardation by HDACi Treatment of the Tumor Embryonal Source

“…Testicular tumors are the most common malignancy in men of European ancestry aged between 15 and 44 years [ 1 , 2 ]. In 2018, more than 71,000 cases of testicular cancer were diagnosed, with over one-third being in Europe.…”

“…This rarely appears as a pure form—only in about 5% of all TGCT cases, and more often as a component of mixed TGCT. The diagnosis of teratoma still relies primarily on classical histopathological and immunohistochemical (IHC) methods of detection [ 1 , 2 , 12 ].…”

Testicular germ cell tumors type 2 have high RNA expression of LDHB, the gene for lactate dehydrogenase subunit B

“…In the previous meta-analysis of the three datasets, EC relatively highly expressed RNA of LIN28A , CCND2 , and NANOG . 16 Nevertheless in the TCGA dataset in our present study, EC expressed RNA of LDHB higher than RNA of ten significant comparative genes ( Figure 4 ).…”

“…The previous meta-analysis of the 24 candidate genes for TGCT type 2 in the three datasets considered CCND2 and NANOG to be driver genes for TGCT type 2. 16 Hence, due to the relatively high RNA expression, our study indicates that also LDHB is a driver gene for TGCT type 2.…”

“…A recent meta-analysis reported how the histologic types of TGCT type 2 expressed RNA of 24 candidate genes for TGCT type 2 in three datasets. 16 Complementarily, our present study aimed to elucidate whether the histologic types of TGCT type 2 differ in RNA expressions of AFP , CGB5 , LDHA , LDHB and LDHC , and to compare RNA expressions of genes for the serum tumor markers with RNA expressions of the 19 previously evaluated candidate genes.…”