Testicular germ cell tumors (TGCTs) are the most common malignancies affecting young men between the ages of 14 and 44, accounting for about 95% of all testicular cancers. Despite being relatively rare compared to other cancers (~3.0 cases per 100,000 population, with high worldwide variability), TGCTs’ incidence is increasing, particularly in industrialized countries. The initial phase of TGCT diagnosis is performed by detecting in the blood the presence of three proteins, i.e., alpha-fetoprotein (AFP), lactate dehydrogenase (LDH), and human chorionic gonadotropin (hCG). Despite these proteins being defined as markers of TGCTs, they present limitations in specificity. Indeed, AFP is not elevated in pure seminomas; LDH serum levels can be elevated in other conditions, such as liver disease or tissue damage, and hCG can be elevated in both seminomas and non-seminomas, reducing its ability to differentiate between tumor types. However, the existence of hCG variants, characterized by distinct glycosylation profiles that are differentially expressed in TGCT types and subtypes, may increase the diagnostic and prognostic potential of this hormone. Furthermore, emerging molecular biomarkers, including miRNAs and tumor cells-related epigenetic status, may offer new promising alternatives to improve diagnostic accuracy. Nonetheless, standardized diagnostic protocols still need to be implemented. Finally, understanding the biological roles of hCG isoforms and their “canonical” (e.g., LHCGR) and “non-canonical” (e.g., TGF-βR) receptor interactions may help in understanding tumor biology and therapeutic targeting.
睾丸生殖细胞肿瘤是影响14至44岁年轻男性最常见的恶性肿瘤，约占所有睾丸癌的95%。尽管与其他癌症相比相对罕见（约每10万人中3.0例，全球差异显著），但其发病率正在上升，尤其在工业化国家。TGCT的初步诊断主要通过检测血液中三种蛋白质的存在来实现，即甲胎蛋白、乳酸脱氢酶和人绒毛膜促性腺激素。尽管这些蛋白质被定义为TGCT的标志物，但其特异性存在局限：AFP在纯精原细胞瘤中并不升高；LDH血清水平可能因肝脏疾病或组织损伤等其他情况而升高；hCG在精原细胞瘤和非精原细胞瘤中均可升高，降低了其区分肿瘤类型的能力。然而，hCG变体因其在TGCT不同类型和亚型中差异表达的糖基化特征，可能提升该激素的诊断和预后潜力。此外，包括miRNA和肿瘤细胞相关表观遗传状态在内的新兴分子生物标志物，可能为提高诊断准确性提供新的有前景的替代方案。尽管如此，标准化诊断方案仍需建立。最后，理解hCG亚型的生物学功能及其与“经典”（如LHCGR）和“非经典”（如TGF-βR）受体的相互作用，可能有助于深入认识肿瘤生物学机制并指导靶向治疗。
肿瘤(癌症)患者之家