Major histocompatibility complex (MHC) class I molecules have a crucial role in tumor immune evasion; however, the association of MHC class I molecules with outcomes in cancer patients remains controversial. Nucleotide-binding oligomerization-like receptor family caspase recruitment domain-containing 5 (NLRC5) has been reported to be a MHC class I transactivator. However, the expression and function of NLRC5 in cancer remains to be elucidated. The present study aimed to retrospectively examine NLRC5 expression in human tumor tissues and its association with clinical outcomes of non-small-cell lung cancer (NSCLC) stage III patients. The expression of MHC class I and NLRC5 in NSCLC were detected using immunohistochemistry (IHC). The association between their expression levels was assessed using the Pearson's χ2 test and their association with survival was assessed using Kaplan-Meier analysis and the log-rank test. In addition, the expression of NLRC5 and MHC class I were examined in 323 cases of seven other types of tumors and their correlations were studied. The results revealed that the expression of NLRC5 was correlated with that of MHC class I in NSCLC patients (P=0.008). MHC class I-positive and nuclear NLRC5-positive NSCLC patients were found to have shorter overall survival (OS) rates (log-rank, P=0.032 and P=0.039, respectively). In addition, in the seven different tumor types, there was a significant correlation between MHC class I and NLRC5 nuclear expression (P<0.001) as well as MHC class I and NLRC5 cytoplasmic expression (P=0.003). In conclusion, NLRC5 was demonstrated to be widely expressed in eight tumor tissues and its expression was correlated with that of MHC class I. Of note, nuclear NLRC5-negative and MHC class I-negative stage III NSCLC patients had improved OS rates compared to those with positive expression. Therefore, NLRC5 and MHC class I may be negative prognostic indicators in NSCLC stage III patients.

Varicocele (VC) is a vascular lesion characterized by dilatation and tortuosity of the spermatic veins. It is commonly found in adolescents and young adults and has an incidence of 4.4–22.6% in the general male population.¹ It is well known that VC is implicated as a cause of infertility in a high percentage of men.^{2, 3} It has been shown that 21–41% of men with primary infertility and 75–81% of those with secondary infertility suffer VC.^{4, 5, 6} Although the physiopathology of VC and its relationship with male infertility have been discussed for the last 50 years, the exact mechanism by which the VC affects spermatogenesis is still unclear.⁷

With the recent increase in the incidence of male infertility, greater attention is being paid to male reproductive health. The causes of male infertility are complex, and damage occurring during any process from spermatogenesis to fertilization can affect sperm quantity and quality of the sperm. Mitochondria are the power sources of cells and help regulate cellular homeostasis and physiological function. Mitochondria play a crucial role in male reproduction. Mitochondria undergo dynamic changes during spermatogenesis, sperm maturation, and fertilization. Mitochondrial dynamics and mitophagy help regulate the structure and function of mitochondria by meeting the cellular energy requirements of sperm during reproduction and reducing levels of damaged mitochondrial DNA (mtDNA); the elimination of excess mtDNA during fertilization prevents the spread of genetic mutations. Stable mitochondrial function ensures the smooth occurrence and maturation of sperm, maintaining male fertility. Externally induced mitochondrial dysfunction can lead to an inadequate energy supply, oxidative stress, cellular apoptosis, and abnormal sperm structure formation, which can lead to male infertility. In this article, the mechanism through which mitochondrial dysfunction affects the entire process of male reproduction, from spermatogonial stem cell division to final fertilization, and leads to infertility is discussed in chronological order. This article explores potential therapeutic targets for improving male fertility through therapies targeting mitochondrial function to provide a reference for subsequent research and more precise treatment directions.