Breast cancer is the most common malignancy and the leading cause of cancer deaths in women worldwide. While specific genetic mutations have been linked to 5–10% of breast cancer cases, other environmental and epigenetic factors influence the development and progression of the cancer. Since unique mutations patterns have been observed in individual cancer samples, identification and characterization of the distinctive breast cancer molecular profile is needed to develop more effective target therapies. Until recently, identifying genetic cancer mutations via personalized DNA sequencing was impractical and expensive. The recent technological advancements in next-generation DNA sequencing, such as the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing cost and time effective with more reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in 105 human breast cancer samples. The sequencing analysis revealed missense mutations in PIK3CA, and TP53 genes in the breast cancer samples of various histologic types. Thus, this study demonstrates the necessity of sequencing individual human cancers in order to develop personalized drugs or combination therapies to effectively target individual, breast cancer-specific mutations.
Colorectal cancer (CRC) is widespread with significant mortality. Both inherited and sporadic mutations in various signaling pathways influence the development and progression of the cancer. Identifying genetic mutations in CRC is important for optimal patient treatment and many approaches currently exist to uncover these mutations, including next-generation sequencing (NGS) and commercially available kits. In the present study, we used a semiconductor-based targeted DNA-sequencing approach to sequence and identify genetic mutations in 91 human rectal cancer samples. Analysis revealed frequent mutations in KRAS (58.2%), TP53 (28.6%), APC (16.5%), FBXW7 (9.9%) and PIK3CA (9.9%), and additional mutations in BRAF, CTNNB1, ERBB2 and SMAD4 were also detected at lesser frequencies. Thirty-eight samples (41.8%) also contained two or more mutations, with common combination mutations occurring between KRAS and TP53 (42.1%), and KRAS and APC (31.6%). DNA sequencing for individual cancers is of clinical importance for targeted drug therapy and the advantages of such targeted gene sequencing over other NGS platforms or commercially available kits in sensitivity, cost and time effectiveness may aid clinicians in treating CRC patients in the near future.
ObjectivesGenome-wide association studies (GWAS) have demonstrated that the single nucleotide polymorphism (SNP) MAP3K1 rs889312 is a genetic susceptibility marker significantly associated with a risk of hormone-related tumors such as breast cancer. Considering steroid hormone-mediated signaling pathways have an important role in the progression of gastric cancer, we hypothesized that MAP3K1 rs889312 may be associated with survival outcomes in gastric cancer. The purpose of this study was to test this hypothesis.MethodsWe genotyped MAP3K1 rs889312 using TaqMan in 884 gastric cancer patients who received subtotal or total gastrectomy. Kaplan-Meier survival analysis and Cox proportional hazard regression were used to analyze the association between MAP3K1 rs889312 genotypes and survival outcomes of gastric cancer.ResultsOur findings reveal that the rs889312 heterozygous AC genotype was significantly associated with an increased rate of mortality among patients with diffuse-type gastric cancer (log-rank P = 0.028 for AC versus AA/CC, hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 1.03–1.69), compared to those carrying the homozygous variant genotypes (AA/CC). Additionally, univariate and multivariate Cox regression analysis demonstrate that rs889312 polymorphism was an independent risk factor for poor survival in these patients.ConclusionsIn conclusion, we demonstrate that MAP3K1 rs889312 is closely correlated with outcome among diffuse-type gastric cancer. This raises the possibility for rs889312 polymorphisms to be used as an independent indicator for predicting the prognosis of diffuse-type gastric cancer within the Chinese population.
Lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) are the two major subtypes of non-small-cell lung cancer (NSCLC). This study aimed to compare mRNA and circRNA expression patterns between LUSC and LUAD. Cancer tissues from 8 LUSC patients and 12 LUAD patients were collected to obtain mRNA and circRNA expression profiles. The differentially expressed mRNAs (DEmRNAs) and circRNAs (DE-circRNAs) between LUSC and LUAD were screened. Afterwards, miRNA-DEcircRNA pairs and miRNA-DEmRNA pairs were predicted to construct a competing endogenous RNAs (ceRNAs) network, followed by functional enrichment analysis and survival analysis. In total, 635 DEmRNAs and 245 DEcircRNAs were obtained. The ceRNA analysis revealed that genes, such as EPHA2, EPHA7, NTRK2, CDK6, hsa_circ_027570, hsa_circ_006089, and hsa-circ_035997, had distinct expression patterns between LUSC and LUAD. Also, functional enrichment analysis indicated that DEmRNAs were mainly enriched in ERK1 and ERK2 cascade. Survival analyses suggested that STXBP1 and PMEPA1 were associated the prognosis of with both LUAD and LUSC, whereas EPHA2 and CDK6 might serve as prognostic factors for LUSC and LUAD, respectively. In conclusion, genes such as EPHA2, EPHA7, NTRK2, and CDK6 had different patterns in the two major histological subtypes of NSCLC. Notably, EPHA2 and CDK6 might be considered as potential therapeutic targets for LUSC and LUAD, respectively.
Malnutrition is a state of altered body composition and body cell mass due to inadequate intake or utilization of energy or nutrients, leading to physical and mental dysfunction and impaired clinical outcomes. As one of the most common geriatric syndromes, malnutrition in the elderly is a significant risk factor for poor clinical outcomes, causing a massive burden on medical resources and society. The risk factors for malnutrition in the elderly are diverse and include demographics, chronic diseases, and psychosocial factors. Presently, recommendations for the prevention and intervention of malnutrition in the elderly are not clear or consistent in China. This consensus is based on the latest global evidence and multiregional clinical experience in China, which aims to standardize the prevention and intervention of malnutrition in the elderly in China and improve the efficacy of clinical practice and the prognosis of elderly patients.
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