Triple-Negative Breast Cancer Analysis Based on Metabolic Gene Classification and Immunotherapy.

Triple negative breast cancer (TNBC) has negative expression of ER, PR and HER-2. TNBC shows high histological grade and positive rate of lymph node metastasis, easy recurrence and distant metastasis. Molecular typing based on metabolic genes can reflect deeper characteristics of breast cancer and provide support for prognostic evaluation and individualized treatment. Metabolic subtypes of TNBC samples based on metabolic genes were determined by consensus clustering. CIBERSORT method was applied to evaluate the score distribution and differential expression of 22 immune cells in the TNBC samples. Linear discriminant analysis (LDA) established a subtype classification feature index. Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves were generated to validate the performance of prognostic metabolic subtypes in different datasets. Finally, we used weighted correlation network analysis (WGCNA) to cluster the TCGA expression profile dataset and screen the co-expression modules of metabolic genes. Consensus clustering of the TCGA cohort/dataset obtained three metabolic subtypes (MC1, MC2, and MC3). The ROC analysis showed a high prognostic performance of the three clusters in different datasets. Specifically, MC1 had the optimal prognosis, MC3 had a poor prognosis, and the three metabolic subtypes had different prognosis. Consistently, the immune characteristic index established based on metabolic subtypes demonstrated that compared with the other two subtypes, MC1 had a higher IFNγ score, T cell lytic activity and lower angiogenesis score, T cell dysfunction and rejection score. TIDE analysis showed that MC1 patients were more likely to benefit from immunotherapy. MC1 patients were more sensitive to immune checkpoint inhibitors and traditional chemotherapy drugs Cisplatin, Paclitaxel, Embelin, and Sorafenib. Multiclass AUC based on RNASeq and GSE datasets were 0.85 and 0.85, respectively. Finally, based on co-expression network analysis, we screened 7 potential gene markers related to metabolic characteristic index, of which CLCA2, REEP6, SPDEF, and CRAT can be used to indicate breast cancer prognosis. Molecular classification related to TNBC metabolism was of great significance for comprehensive understanding of the molecular pathological characteristics of TNBC, contributing to the exploration of reliable markers for early diagnosis of TNBC and predicting metastasis and recurrence, improvement of the TNBC staging system, guiding individualized treatment.

Genetic susceptibility of eight nonsynonymous polymorphisms in HLA-DRB1 gene to hepatocellular carcinoma in Han Chinese.

Backgrounds and Objective: Mounting evidence suggests that human leukocyte antigen (HLA) plays a central role in anti-virus and tumor defense. To test whether genetic variation in HLA-DRB1 gene, a key component of HLA system, can predict its predisposition to hepatocellular carcinoma (HCC), we thereby conducted an association study by genotyping 8 nonsynonymous polymorphisms in HLA-DRB1 gene among 257 HCC patients and 264 controls. RESULTS: All polymorphisms respected the Hardy-Weinberg equilibrium. The genotypes and alleles of rs17879599 differed significantly between patients and controls after Bonferroni correction (both P < 0.001), and the power to detect this significance was 94.4%. After adjusting for age, gender, smoking, drinking and hepatitis infection, the mutant allele of rs17879702 was significantly associated with an increased risk for HCC under additive (odds ratio [OR] = 2.12, 95% confidence interval [CI]: 1.20-4.02, P = 0.004) and dominant (OR = 2.51, 95% CI: 1.39-2.96, P = 0.004) models. Haplotype analysis indicated that haplotype A-T-C-T-G-C-T-A (alleles ordered by rs199514452, rs201540428, rs201614260, rs17879702, rs17880292, rs17879599, rs17424145 and rs35445101) was overrepresented in patients and enhanced predisposition to HCC (adjusted OR = 2.72, 95% CI: 1.24-5.78, P = 0.004). In cumulative analysis, carriers of 7-9 unfavorable alleles had a 2.41-fold (95% CI: 1.18-4.92, P = 0.016) increased risk for HCC after adjusting for confounding factors relative to those possessing 4 or less unfavorable alleles. MATERIALS AND METHODS: Genotypes were determined by ligase detection reaction. HCC patients were newly diagnosed, histopathologically confirmed or previously untreated and controls were cancer-free. CONCLUSIONS: Our findings suggest an independent leading contribution of rs17879599 in the 2nd exon of HLA-DRB1 gene to HCC risk in Han Chinese.

Dorsal penile nerves and primary premature ejaculation.

BACKGROUND: Based on our clinical experience, the number of dorsal penile nerves in patients with primary premature ejaculation (PPE) is not consistent with the average number (2 branches). In this study, we evaluated the number and distribution of dorsal penile nerves among healthy Chinese adults and patients with PPE. METHODS: The dorsal nerve of the penis, the deep dorsal vein of the penis, and the dorsal artery of the penis between the deep fascia of the penis and the albuginea penis were carefully educed, observed, and counted in 38 adult autopsy specimens. The number and distribution of the dorsal penile nerve in 128 surgical patients with PPE were determined. RESULTS: The numbers of dorsal penile nerves of the 38 cases were as follows: 7 branches in 1 case; 6 branches in 1 case; 5 branches in 6 cases; 4 branches in 9 cases; 3 branches in 14 cases; and 2 branches in 7 cases. Most of the dorsal nerves were parallel to each other and in the dorsum of the penis. In only 8 cases, the branches were connected by some communicating branches. In 4 cases, 1 or 2 thin dorsal nerves continued their pathway over the ventral aspect of the penis. The average number of branches of the dorsal penile nerve in patients with PPE was 7.16. CONCLUSIONS: Based on the study of 38 cases, the average number of dorsal penile nerves was 3.55 branches and that of patients with PPE was greater. These preliminary results suggest that the excessive dorsal penile nerves may have an impact on PPE via increased sensitivity and provide topographic data for the possible treatment of PPE.