Prostate cancer (PCa) is the most commonly diagnosed neoplasm among men. Since it often resembles benign prostate hyperplasia (BPH), biomarkers with a higher differential value than PSA are required. Epigenetic biomarkers in liquid biopsies, especially miRNA, could address this challenge. The absolute expression of miR-375-3p, miR-182-5p, miR-21-5p, and miR-148a-3p were quantified in blood plasma and seminal plasma of 65 PCa and 58 BPH patients by digital droplet PCR. The sensitivity and specificity of these microRNAs were determined using ROC curve analysis. The higher expression of miR-182-5p and miR-375-3p in the blood plasma of PCa patients was statistically significant as compared to BPH (p = 0.0363 and 0.0226, respectively). Their combination achieved a specificity of 90.2% for predicting positive or negative biopsy results, while PSA cut-off of 4 µg/L performed with only 1.7% specificity. In seminal plasma, miR-375-3p, miR-182-5p, and miR-21-5p showed a statistically significantly higher expression in PCa patients with PSA >10 µg/L compared to ones with PSA ≤10 µg/L. MiR-182-5p and miR-375-3p in blood plasma show higher performance than PSA in discriminating PCa from BPH. Seminal plasma requires further investigation as it represents an obvious source for PCa biomarker identification.

RASSF1A represents one of the eight isoforms of the RASSF1 gene. RASSF1A is a tumor suppressor gene whose inactivation influences tumor initiation and development. In cancer, RASSF1A is frequently inactivated by mutations, loss of heterozygosity and, most commonly, by promoter hypermethylation. As epigenetic inactivation of RASSF1A was detected in various cancer types, it was extensively investigated and nowadays, the research on RASSF1A promoter methylation proceeds in the light of an epigenetic tumor biomarker. Analyses of DNA methylation of genes involved in carcinogenesis such as RASSF1A are currently done mostly on genomic DNA (gDNA). Simultaneously, cell-free DNA (cfDNA) from liquid biopsies has lately been developed as an early cancer diagnostic tool. This review discusses the evidence on aberrantly methylated RASSF1A in gDNA and cfDNA from different cancer types and its utility for early cancer diagnosis, prognosis, and surveillance. Furthermore, methylation frequencies of RASSF1A in gDNA and cfDNA were compared in various cancer types. The weaknesses and strengths of the investigations mentioned above are discussed. In conclusion, although the importance of RASSSF1A methylation in relation to cancer was established, and it became included in several diagnostic panels, the evidence of its diagnostic utility is still experimental and not yet implemented in standard clinical health care.

Male reproductive development starts early in the embryogenesis with somatic and germ cell differentiation in the testis. The LIN28 family of RNA-binding proteins promoting pluripotency has two members—LIN28A and LIN28B. Their function in the testis has been investigated but many questions about their exact role based on the expression patterns remain unclear. LIN28 expression is detected in the gonocytes and the migrating, mitotically active germ cells of the fetal testis. Postnatal expression of LIN28 A and B showed differential expression, with LIN28A expressed in the undifferentiated spermatogonia and LIN28B in the elongating spermatids and Leydig cells. LIN28 interferes with many signaling pathways, leading to cell proliferation, and it is involved in important testicular physiological processes, such as cell renewal, maturation, fertility, and aging. In addition, aberrant LIN28 expression is associated with testicular cancer and testicular disorders, such as hypogonadotropic hypogonadism and Klinefelter’s syndrome. This comprehensive review encompasses current knowledge of the function of LIN28 paralogs in testis and other tissues and cells because many studies suggest LIN28AB as a promising target for developing novel therapeutic agents.

Testicular germ cell tumors (TGCTs) are ever more affecting the young male population. Germ cell neoplasia in situ (GCNIS) is the origin of TGCTs, namely, seminomas (SE) and a heterogeneous group of nonseminomas (NS) comprising embryonal carcinoma, teratoma, yolk sac tumor, and choriocarcinoma. Response to the treatment and prognosis, especially of NS, depend on precise diagnosis with a necessity for discovery of new biomarkers. We aimed to perform comprehensive in silico analysis at the DNA, RNA, and protein levels of six prospective (HOXA9, MGMT, CFC1, PRSS21, RASSF1A, and MAGEC2) and six known TGCT biomarkers (OCT4, SOX17, SOX2, SALL4, NANOG, and KIT) and assess its congruence with histopathological analysis in all forms of TGCTs. Cancer Hallmarks Analytics Tool, the Search Tool for the Retrieval of Interacting Genes/Proteins database, and UALCAN, an interactive web resource for analyzing cancer OMICS data, were used. In 108 TGCT and 48 tumor-free testicular samples, the immunoreactivity score (IRS) was calculated. SE showed higher frequency in DNA alteration, while DNA methylation was significantly higher for all prospective biomarkers in NS. In GCNIS, we assessed the clinical positivity of RASSF1 and PRSS21 in 52 and 62 of samples, respectively, in contrast to low or nil positivity in healthy seminiferous tubules, TGTCs as a group, SE, NS, or all NS components. Although present in approximately 80 of healthy seminiferous tubules (HT) and GCNIS, HOXA9 was diagnostically positive in 64 of TGCTs, while it was positive in 82 of NS versus 29 of SE. Results at the DNA, mRNA, and protein levels on putative and already known biomarkers were included in the suggested panels that may prove to be important for better diagnostics of various forms of TGCTs.