Testicular cancers are considered a relatively rare type of cancer. It accounts for approximately 1% of all cancers in both pediatric and adult men [18]. Although it mainly affects young adults, it can also be seen in children and the elderly. However, despite its importance, research on testicular cancer, especially in pediatric cases, has been relatively limited compared to other types of cancer [19].
Collagen, the primary constituent of the extracellular matrix, exists in various tissues, including the testis. Prolidase, functioning as an iminodipeptidase enzyme, operates as a homodimer, releasing carboxy-terminal proline or hydroxyproline from oligopeptides. Its well-established role encompasses involvement in the collagen cycle, matrix remodeling, and cellular growth [20]. In the realm of humans, the prolidase enzyme seems to predominantly engage in metabolizing products resulting from collagen breakdown, while simultaneously repurposing proline from dipeptides, all to contribute to the subsequent synthesis of collagen. [21]. Moreover, there has been a suggestion that the enzymatic activity of prolidase might function as a constraining element in overseeing the regulation of collagen synthesis [22].
The facilitated breakdown of tissue barriers by proteolytic enzymes released from primary tumors is widely accepted [23]. Consequently, the tumor's progression relies heavily on the degradation of collagen and other extracellular matrix (ECM) proteins [24]. Among the essential enzymes responsible for ECM protein degradation, Matrix metalloproteinases (MMPs) play a pivotal role. While serum prolidase activity has been extensively studied in specific cancers, the precise underlying cause remains unknown [25, 26]. Some researchers have reported heightened prolidase activities in lung cancer, gastric cancer, and ovarian cancer [27, 28]. Conversely, a divergent perspective emerges from the study by Palka and colleagues, wherein they observed a reduction in the activity of the prolidase enzyme specifically within the context of pancreatic cancer [29]. As a result of these studies that have been going on for about 30 years, it is obvious that more studies should be done.
Within our current investigation, a distinct observation emerged as we identified substantially elevated serum prolidase activities within individuals afflicted by testicular cancer, surpassing those of the healthy control group. Interestingly, our exploration marks uncharted territory, as the evaluation of serum prolidase activity in the context of testicular cancer has not previously been undertaken. As such, this undertaking stands as the inaugural endeavor delving into the assessment of serum prolidase activity among patients grappling with testicular cancer.
While there exists a certain grasp upon potential mechanisms that orchestrate the regulatory role of oxidative stress in tumor growth and progression—encompassing aspects like genomic instability, activation of oncogenes, and the intricacies of angiogenesis—there persists an array of pressing inquiries that await comprehensive answers. It is not clearly known whether oxidative stress and tumor development result from increased oxidant production or from a failure of antioxidant systems [30, 31]. While experimental models have showcased considerable shifts in the equilibrium of cellular redox status throughout the trajectory of tumor development, comparable occurrences of such transformations have yet to be verified within the human context. The complexities of the biochemical pathways regulating cellular redox balance pose considerable challenges in these investigations. Various oxidizing molecules, including reactive oxygen species (ROS) and depleting agents, can modify the state of glutathione redox. The equilibrium is commonly under the influence of glutathione-consuming enzymes (like glutathione peroxidase) and restoring enzymes (such as glutathione reductase). The exploration into glutathione (GSH) and associated enzymes, along with their potential variances in the context of tumors, has yet to receive comprehensive scrutiny [32].
As a result of this study, we examined measurements including SOD activity and MDA levels in addition to GSH levels and activities of GSH-dependent enzymes (GSH-Px and GST). These analyzes were conducted to provide a comprehensive assessment of the concurrent mechanisms of oxidative stress and antioxidants in individuals diagnosed with testicular cancer. Findings from this research revealed a compelling narrative. MDA levels witnessed a notable increase in the testicular cancer context, in stark contrast to their counterparts in the control group. Conversely, a different pattern emerged, indicating significantly reduced levels of SOD, GSH-Px, and GST among people diagnosed with testicular cancer.
Elevated lipid peroxidation (LP) arises from aberrant cellular proliferation within the serum of individuals grappling with cancer. This surge in LP levels could, in part, be attributed to the compromised antioxidant system, an aspect documented in earlier research endeavors. Notably, the compound malondialdehyde (MDA) has been implicated as a potential catalyst for tumor progression and cocarcinogenesis, given its substantial cytotoxicity and its propensity to hamper protective enzyme functions. However, there exists an ongoing debate within the literature regarding the precise levels of MDA across diverse human cancer variants.
On another front, MDA, which emerges as the principal aldehyde end product stemming from LP involving membrane polyunsaturated fatty acids and triggered by free radicals, serves as an emblematic sign of oxidative stress. A novel dimension unfolds within the scope of this present study, wherein a profound elevation in serum MDA levels became evident among patients who have been diagnosed with testicular cancer, setting them apart from their healthy counterparts [33, 34, 35].
The discourse surrounding the information cataloged within existing literature regarding oxidant, antioxidant molecules, and enzyme dynamics across distinct human cancer classifications remains entwined with controversy. This intricate landscape is exemplified by instances such as a particular investigation, where the activities of enzymes SOD and GSH-Px were disclosed to be notably subdued within malignant liver tissues during the course of rat hepatocarcinogenesis. In another illuminating study, the pioneering work of Corrocher et al. uncovered a stark revelation: within human hepatoma scenarios, the enzymatic antioxidant network faced severe impediments, primarily stemming from a palpable diminution in GSH-Px activities. A parallel narrative emerges through the study undertaken by Aceto et al., where diminished GSH-Px activity resonated in the testicular tissues of prostate cancer patients. Expanding the scope, Van Balgooy and Roberts' exploration unearthed a decline in SOD activities within disparate malignant tissue types. It remains noteworthy, however, that the domain of testicular carcinomas has, until this juncture, received comparatively lesser attention in these realms of inquiry [36, 37, 38].
In our study investigating testicular tumors in both pediatric and adult populations, we obtained similar results regarding peroxidase activity and oxidative stress markers, as reported in previous similar studies. Given the lack of previous investigations specifically focused on testicular tumors, we considered the obtained results to be significant. It should be noted that the limited number of cases is attributed to the rarity of testicular cancers in both adult and pediatric populations. Histopathological analysis revealed that, in line with the literature, seminoma was the most commonly observed subtype. Additionally, we did not encounter cases of gonadoblastoma, as no conditions such as streak gonad or undescended testis were observed.
Based on the results obtained from our study, it has been observed that there is a likelihood of an increase in the process of collagen turnover in patients who have been diagnosed with testicular cancer. Additionally, our findings suggest a possible link between elevated levels of prolidase and an elevated state of oxidative stress, which is accompanied by a decrease in the levels of antioxidants in cases involving testicular cancer.
In conclusion, it can be said that increased prolidase activity potentially contributes to the development of testicular cancer, albeit partially. Considering these findings in our study, it can be thought that the use of antioxidant vitamins for testicular cancer may be beneficial in both preventive measures and treatment approaches. The fact that the number of patients was not high should be attributed to the fact that the study was evaluated within the limitations and that testicular cancer was not observed very often. It should also be considered that all age groups are evaluated together.