Background Cuproptosis, a newly discovered mode of cell death, has been less studied in hepatocellular carcinoma (HCC). Exploring the molecular characteristics of different subtypes of HCC based on cuproptosis-related genes (CRGs) is meaningful to HCC. In addition, immunotherapy plays a pivotal role in treating HCC. Exploring the sensitivity of immunotherapy and building predictive models are critical for HCC. Methods The 357 HCC samples from the TCGA database were classified into three subtypes, Cluster 1, Cluster 2, and Cluster 3, based on the expression levels of ten CRGs genes using consensus clustering. Six machine learning algorithms were used to build models that identified the three subtypes. The molecular features of the three subtypes were analyzed and compared from some perspectives. Moreover, based on the differentially expressed genes (DEGs) between Cluster 1 and Cluster 3, a prognostic scoring model was constructed using LASSO regression and Cox regression, and the scoring model was used to predict the efficacy of immunotherapy in the IMvigor210 cohort. Results Cluster 3 had the worst overall survival compared to Cluster 1 and Cluster 2 (P = 0.0048). The AUC of the Catboost model used to identify Cluster 3 was 0.959. Cluster 3 was significantly different from the other two subtypes in gene mutation, tumor mutation burden, tumor microenvironment, the expression of immune checkpoint inhibitor genes and N6-methyladenosine regulatory genes, and the sensitivity to sorafenib. We believe Cluster 3 is more sensitive to immunotherapy from the above analysis results. Therefore, based on the DEGs between Cluster 1 and Cluster 3, we obtained a 7-gene scoring prognostic model, which achieved meaningful results in predicting immunotherapy efficacy in the IMvigor210 cohort (P = 0.013). Conclusions Our study provides new ideas for molecular characterization and immunotherapy of HCC from machine learning and bioinformatics. Moreover, we successfully constructed a prognostic model of immunotherapy.

Editorial on the Research Topic Molecular and cytogenetic research advances in human reproductionvolume IIInfertility is a prevalent disorder that affects over 15% of couples worldwide, with various causes such as meiotic arrest due to cytogenetic shuffling, toxins, and other physical factors (1-4). Among the genetic causes of male infertility, chromosomal abnormalities have been reported in approximately 6% of cases, and microdeletions in the Y chromosome account for spermatogenic failure in 5-20% of men with azoospermia (3, 5-8). The most common structural Y chromosome aberrations in infertile men with azoospermia have been reported to be an isodicentric or isochromosome Y, with duplications in the Yp region and deletions in the Yq region, or vice versa (9-12). The human X and Y chromosomes pair at their distal short arms during male meiosis, with the telomeres first approaching each other during the zygotene stage of meiotic prophase (13, 14). As pachytene progresses, a paired segment is formed, and a synaptonemal complex (SC) which, on average, extends to about one-third of the total length of the Y chromosome (15-17).Recently, pathogenic genetic mutations have been identified in individuals suffering from reproductive disorders; these mutations are generally detected in the genes mainly involved in germ cell development and other reproductive processes (18-21). Nevertheless, thousands of functionally relevant genes are expressed in human testes and ovaries, and malfunctioning of even a single gene can potentially cause infertility (22)(23)(24). Although the overall mechanistic contribution of specific genes has been studied in animal models, more attention is now being paid to clinically detected alterations in DNA, which include mutations potentially affecting gene regulatory sequences such as the 3'UTR (25, 26). However, the impact of mutations in gene 3'UTR sequences may not be adequately recognized in current sequencing analyses. This provides a potentially massive gap between Frontiers in Endocrinology frontiersin.org 01