Circulating tumor cells (CTCs) are known to be heterogeneous and clustered with tumor-associated cells, such as macrophages, neutrophils, fibroblasts, and platelets. However, their molecular profile and clinical significance remain largely unknown. Thus, we aimed to perform a comprehensive gene expression analysis of single CTCs and CTC clusters in patients with pancreatic cancer and to identify their potential clinical relevance to provide personalized medicine. Epitope-independent, rapid (>3 mL of whole blood/min) isolation of single CTCs and CTC clusters was achieved from a prospective cohort of 16 patients with unresectable pancreatic cancer using a centrifugal microfluidic device. Forty-eight mRNA expressions of individual CTCs and CTC clusters were analyzed to identify pancreatic CTC phenotype. CTC clusters had a larger proportion of mesenchymal expression than single CTCs (p = 0.0004). The presence of CTC clusters positively correlated with poor prognosis (progression-free survival, p = 0.0159; overall survival, p = 0.0186). Furthermore, we found that most CTCs in these patients (90.7%) were cloaked with platelets and found the presence of a positive correlation between the increase in CTC clusters and rapid disease progression during follow-ups. Efficient CTC cluster isolation and analysis techniques will enhance the understanding of complex tumor metastasis processes and can facilitate personalized disease management.
Although physical activity (PA) is beneficial for prolonging lifespan, evidence for the protective role of PA against the development of gastric cancer (GC) is not yet well established. This study assessed the association between PA and GC risk in patients with and without Helicobacter pylori (H. pylori) infection in a Korean population. In total, 415 GC patients and 830 controls were enrolled at the National Cancer Center, Korea. The International Physical Activity Questionnaire-Short Form was used to collect PA data. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. In the H. pylori-positive group, subjects who engaged in regular exercise showed a significantly reduced risk of GC in the entire population (OR = 0.52, 95% CI = 0.38–0.70) and in females (OR = 0.60, 95% CI = 0.21–0.64). Subjects who engaged in a high level of total PA showed a significantly reduced risk of GC relative to subjects in the lowest tertile in the fully adjusted model (OR = 0.46, 95% CI = 0.32–0.65, p-trend < 0.001). There was an inverse association between PA and GC risk in the entire population, and in the H. pylori-positive subgroup. Our data indicate the need for the promotion of all domains of PA, especially for Korean populations.
Postprandial hypotension (PPH) is common among the elderly. However, it is unknown whether the presence of PPH can predict the development of new cardiovascular disease (CVD) in the elderly during the long-term period. This study aimed to prospectively evaluate the presence of PPH and the development of new CVD within a 36 month period in 94 community-dwelling elderly people without a history of CVD. PPH was diagnosed in 47 (50.0%) participants at baseline and in 7 (7.4%) during the follow-up period. Thirty participants (31.9%) developed new CVD within 36 months. We performed a time-dependent Cox regression analysis with PPH, hypertension, diabetes, and body mass index (BMI) as time-varying covariates. In the univariate analyses, the presence of PPH, higher BMI, hypertension, diabetes mellitus, and higher systolic and diastolic blood pressure were associated with the development of new CVD. The multivariate analysis indicated that the relationship between PPH and the development of new CVD remained (adjusted hazard ratio 11.18, 95% confidence interval 2.43–51.38, p = 0.002) even after controlling for other variables as covariates. In conclusion, the presence of PPH can predict the development of new CVD. Elderly people with PPH may require close surveillance to prevent CVD.
Gastric cancer (GC) is one of the most common cancers and a leading cause of cancer deaths around the world. Chemotherapy is one of the most effective treatments for cancer patients, and has remarkably enhanced survival rates. However, it has many side effects. Recently, microRNAs (miRNAs) have been intensively studied as potential biomarkers for cancer diagnosis and treatment monitoring. However, definitive biomarkers in chemotherapy-induced peripheral neuropathy (CIPN) are still lacking. The aim of this study was to identify the factors significant for neurological adverse events in GC patients receiving XELOX (oxaliplatin and capecitabine) chemotherapy. The results show that XELOX chemotherapy induces changes in the expression of hsa-miR-200c-3p, hsa-miR-885-5p, and hsa-miR-378f. Validation by qRT-PCR demonstrated that hsa-miR-378f was significantly downregulated in CIPN. Hsa-miR-378f was identified as showing a statistically significant correlation in GC patients receiving XELOX chemotherapy according to the analysis of differentially expressed (DE) miRNAs. Furthermore, 34 potential target genes were predicted using a web-based database for miRNA target prognostication and functional annotations. The identified genes are related to the peptidyl-serine phosphorylation and regulation of alternative mRNA splicing with enrichment in the gastric cancer, neurotrophin, MAPK, and AMPK signaling pathways. Collectively, these results provide information useful for developing promising strategies for the treatment of XELOX-chemotherapy-induced peripheral neuropathy.
Background: Gastric cancer (GC) is among the most common types of gastrointestinal cancers and has a high incidence and mortality around the world. To suppress the progression of GC, it is essential to develop diagnostic markers. MicroRNAs regulate GC development, but a clearer insight into their role is needed before they can be applied as a molecular markers and targets.Methods: In this study, we assessed the diagnostic value of differentially expressed microRNAs as potential diagnostic biomarkers for GC using data for 389 tissue samples from the Cancer Genome Atlas (TCGA) and 21 plasma samples from GC patients.Results: The expression of hsa-miR-143-3p (also known as hsa-miR-143) was significantly downregulated in GC according to the TCGA data and plasma samples. The 228 potential target genes of hsa-miR-143-3p were analyzed using a bioinformatics tool for miRNA target prediction. The target genes correlated with extracellular matrix organization, the cytoplasm, and identical protein binding. Furthermore, the pathway enrichment analysis of target genes showed that they were involved in pathways in cancer, the phosphoinositide 3-kinase (PI3K)–protein kinase B (Akt) signaling pathway, and proteoglycans in cancer. The hub genes in the protein–protein interaction (PPI) network, were matrix metallopeptidase 2 (MMP2), CD44 molecule (CD44), and SMAD family member 3 (SMAD3).Conclusions: This study suggests that hsa-miR-143-3p may be used as a diagnostic marker for GC, contributing via the pathways involved in the development of GC.