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Cancer is one of the most concerning public health issues and breast cancer is one of the most common cancers in the world. The immune cells within the tumor microenvironment regulate cancer development. In this study, single immune cell data sets were used to identify marker gene sets for exhausted CD8 + T cells (CD8Tex) in breast cancer. Machine learning methods were used to cluster subtypes and establish the prognostic models with breast cancer bulk data using the gene sets to evaluate the impacts of CD8Tex. We analyzed breast cancer overexpressing and survival-associated marker genes and identified CD8Tex hub genes in the protein-protein-interaction network. The relevance of the hub genes for CD8 + T-cells in breast cancer was evaluated. The clinical associations of the hub genes were analyzed using bulk sequencing data and spatial sequencing data. The pan-cancer expression, survival, and immune association of the hub genes were analyzed. We identified biomarker gene sets for CD8Tex in breast cancer. CD8Tex-based subtyping systems and prognostic models performed well in the separation of patients with different immune relevance and survival. CRTAM, CLEC2D, and KLRB1 were identified as CD8Tex hub genes and were demonstrated to have potential clinical relevance and immune therapy impact. This study provides a unique view of the critical CD8Tex hub genes for cancer immune therapy., (© 2024. The Author(s).)

Acral melanoma (AM) is a subtype of melanoma with high prevalence in East Asians. AM is characterized by greater aggressiveness and lower survival rates. However, there are still fewer studies on immune mechanisms of AM especially subungual melanoma (SM) versus non-subungual melanoma (NSM). In order to explore tumor heterogeneity and immune microenvironment in different subtypes of AM, we applied single-cell RNA sequencing to 24,789 single cells isolated from the SM and plantar melanoma (PM) patients. Aspects of tumor heterogeneity, melanocytes from PM and SM had significant differences in gene expression, CNV and pathways in which tumor-associated such as NF-kb and Wnt were involved. Regarding the immune microenvironment, PM contained more fibroblasts and T/NK cells. The EPHA3-EFNA1 axis was expressed only in cancer-associated fibroblast (CAF) and melanocytes of PM, and the TIGIT-NECTIN2 axis was expressed in both AM subtypes of T/NK cells and melanocytes. Altogether, our study helps to elucidate the tumor heterogeneity in AM subpopulations and provides potential therapeutic targets for clinical research., (© 2024. The Author(s).)

A hospital-based case-control study was conducted to investigate potential association between mitochondrial DNA and Type 2 diabetes mellitus (T2DM) in Chinese Uyghur population. We sequenced mitochondrial DNA from 210 Uyghur individuals including 88 T2DM patients and 122 controls. Using haplogroup classification and association test, we found that haplogroup H (odds ratio [OR] = 1.40; 95% confidence interval [CI]: 1.20-1.64; P = 0.0005138) and D4 (odds ratio = 1.47; 95% CI: 1.22-1.77; P = 0.001064) were associated with an increased risk of T2DM in Chinese Uyghur population. Two markers of haplogroup D4 and H, MT-ATP8 m.8414 T > G (p.Leu17Phe) and m.2706 G > A encoding 16S rRNA in mitochondria, were predicted to affect the structure of MT-ATP8 and 16S RNA, respectively, and may be involved in the pathogenesis of T2DM. Our study provides a new clue for mitochondrial DNA in the etiology of T2DM in Chinese Uyghur population.

The purpose was to explore the effects of resting heart rate (RHR) and pulse pressure (PP) independently as well as their cumulative effects on the risk of type 2 diabetes mellitus (T2DM) through cross-sectional study plus meta-analysis. A total of 8276 subjects aged 35-74 years from the Rural Diabetes, Obesity and Lifestyle (RuralDiab) study were included in the study. Meanwhile, two meta-analyses were conducted to validate the results of the epidemiological research. The results showed that RHR and PP were associated with higher risk of T2DM, and the corresponding adjusted OR(95%CI) for each quartiles were 1.00, 0.99(0.68-1.42), 1.58(1.13-2.20), 2.93(2.15-3.98) and 1.00, 1.06(0.75-1.48), 1.11(0.79-1.56), 1.45(1.03-2.03), respectively. The cumulative effect analysis indicated that the adjusted OR(95%CI) in the fast RHR-high PP were 3.36(2.26-4.99), 2.60(1.47-4.59), and 3.60(2.09-6.20) compared with the slow RHR-low PP for total population, male and female, respectively. Meta-analysis showed that the pooled effect values for RHR and PP were 1.94(1.64-2.31) and 1.25(1.04-1.51), respectively. This study demonstrated that elevated RHR and PP are independently associated with the risk of T2DM as well as the influences of conventional confounders, and fast RHR with high PP might cumulatively increase the risk of T2DM. However, the potential clinical application remains to be determined.