Objective
To evaluate the ability of Epithelial-to-mesenchymal transition (EMT)-related microRNAs (miRNAs) as serum biomarkers for prognosis and prediction of metastasis in colorectal cancer (CRC) patients.
Background
EMT-related miRNAs drive CRC progression and metastasis. However, their potential as serum biomarkers in CRC has not been studied.
Methods
This was a three-phase study using 446 colorectal specimens. In the first phase, we selected candidate miRNAs associated with metastasis by analyzing the expression of four miR-200 family members (miR-200b, -200c, -141 and -429) in serum samples from 12 stage I and IV CRC patients. The second phase involved independent validation of candidate miRNAs in serum from 182 CRC patients and 24 controls. Lastly, we analyzed expression in matched 156 tumor tissues from 182 CRC patients, as well as an independent set of 20 matched primary CRC and corresponding liver metastases to identify source of circulating miRNAs.
RESULTS
Following initial screening, miR-200c was selected as the candidate serum miRNA best associated with metastasis. Validation analysis revealed that serum miR-200c levels were significantly higher in stage IV compared with stage I–III CRCs. High serum miR-200c demonstrated a significant positive correlation with lymph node, distant metastasis and prognosis (P=0.0026, P=0.0023 and P=0.0064, respectively). More importantly, serum miR-200c was an independent predictor for lymph node metastasis (OR=4.81, 95% CI=1.98–11.7 P=0.0005), tumor recurrence (HR=4.51, 95% CI=1.56–13.01 P=0.005) and emerged as an independent prognostic marker for CRC (HR: 2.67, 95%CI: 1.28–5.67, P=0.01).
CONCLUSION
Serum miR-200c has a strong potential to serve as a noninvasive biomarker for CRC prognosis and predicting metastasis.
OBJECTIVE To use the concept of benchmarking to establish robust and standardized outcome references after pancreatico-duodenectomy (PD). BACKGROUND Best achievable results after PD are unknown. Consequently, outcome comparisons among different cohorts, centers or with novel surgical techniques remain speculative. METHODS This multicenter study analyzes consecutive patients (2012-2015) undergoing PD in 23 international expert centers in pancreas surgery. Outcomes in patients without significant comorbidities and major vascular resection (benchmark cases) were analyzed to establish 20 outcome benchmarks for PD. These benchmarks were tested in a cohort with a poorer preoperative physical status (ASA class 3) and a cohort treated by minimally invasive approaches. RESULTS Two thousand three hundred seventy-five (38%) low-risk cases out of a total of 6186 PDs were analyzed, disclosing low in-hospital mortality (1.6%) but high morbidity, with a 73% benchmark morbidity rate cumulated within 6 months following surgery. Benchmark cutoffs for pancreatic fistulas (B-C), severe complications (grade 3), and failure-to-rescue rate were 19%, 30%, and 9%, respectively. The ASA 3 cohort showed comparable morbidity but a higher in hospital-mortality (3% vs 1.6%) and failure-to-rescue rate (16% vs 9%) than the benchmarks. The proportion of benchmark cases performed varied greatly across centers and continents for both open (9%-93%) and minimally invasive (11%-62%) PD. Centers operating mostly on complex PD cases disclosed better results than those with a majority of low-risk cases. CONCLUSION The proposed outcome benchmarks for PD, established in a large-scale international patient cohort and tested in 2 different cohorts, may allow for meaningful comparisons between different patient cohorts, centers, countries, and surgical techniques.
The plant-pathogenic prokaryote Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight, one of the most important diseases of rice. The bacterium is a model organism for the analysis of plant-pathogen interaction, because more than 30 races differing in virulence and 25 resistance genes in rice have been reported to date. We present here the complete genome sequence of Xoo strain MAFF 311018. The size of the genome was 4,940,217 bp, in a single circular chromosome. The genome structure of Xoo MAFF 311018 was characterized by large numbers of effector (avr) genes of the avrBs3/pth family and insertion sequences (ISs). RFLP analysis of diverse strains using ISXo1 as a probe suggests that the prevalence of mobile elements in this species, which can bring about genome inversions and rearrangement, may have played a major role in generating the high degree of genetic diversity and race differentiation characteristic of this pathogen. The Xoo MAFF 311018 sequence was also highly similar to those of X. axonopodis pv. citri and X. campestris pv. campestris with the exception of the large number of effectors and IS elements, and numerous inversions and rearrangements.
The prognosis of gastric cancer (GC) patients with peritoneal dissemination remains poor, and a better understanding of the underlying mechanisms is critical for the development of new treatments that will improve survival in these patients. This study aimed to clarify the clinical and biological role of two key metastasis-associated long non-coding RNAs (lncRNAs) in GC. We analyzed the expression levels of two lncRNAs-Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) and HOX-Antisense Intergenic RNA (HOTAIR)-by real-time reverse transcription PCR in 300 gastric tissues (150 GC and 150 adjacent normal mucosa), and in seven GC cell lines. Functional characterization for the role of HOTAIR in GC was performed by small interfering RNA (siRNA) knockdown, followed by series of in-vitro and in-vivo experiments. Expression of both lncRNAs was significantly higher in cancerous tissues than in corresponding normal mucosa, and higher expression of these lncRNAs significantly correlated with peritoneal metastasis in GC patients. In addition, elevated HOTAIR expression emerged both as an independent prognostic and risk factor for peritoneal dissemination. SiRNA knockdown of HOTAIR in GC cells significantly inhibited cell proliferation, migration and invasion, but concurrently enhanced the anoikis rate in transfected cells. In an in vivo assay, HOTAIR siRNA-transfected MKN45 cells injected into nude mice inhibited the growth of xenograft tumors and peritoneal metastasis compared with controls. Our data provide novel evidence for the biological and clinical significance of HOTAIR expression as a potential biomarker for identifying patients with peritoneal metastasis, and as a novel therapeutic target in patients with gastric neoplasia.
Although the organization of KRWs is in flux as the system of hospitals grows, results over the past 8 years suggest that changes in national insurance policies are affecting the quantity and organization of rehabilitation interventions and improvement in patient outcomes.
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