Background: Outcome prediction for patients with sepsis may be conductive to early aggressive interventions. Numerous biomarkers and multiple scoring systems have been utilized in predicting outcomes, however, these tools were either expensive or inconvenient. We performed a meta-analysis to evaluate the prognostic role of red blood cell distribution width (RDW) in patients with sepsis. Methods: The online databases of Embase, Web of science, Pubmed, Corchrane library, Chinese Wanfang database, CNKI database were systematically searched from the inception dates to June, 24th, 2020, using the keywords red cell distribution width and sepsis. The odds ratio (OR) or Hazards ratio (HR) with corresponding 95% confidence intervals (95%CI) were pooled to evaluate the association between baseline RDW and sepsis. A random-effects model was used to pool the data, and statistical heterogeneity between studies was evaluated using the I2 statistic. Sensitivity and subgroup analyses were performed to detect the publication bias and origin of heterogeneity. Results: Eleven studies with 17,961 patients with sepsis were included in the meta-analysis. The pooled analyses indicated that increased baseline RDW was associated with mortality (HR = 1.14, 95%CI 1.09–1.20, Z = 5.78, P < 0.001) with significant heterogeneity (I2 = 80%, Pheterogeneity < 0.001). Similar results were found in the subgroup analysis stratified by site of infection, comorbidity, Newcastle-Ottawa Scale (NOS) score, study design, patients’ country. The predefined subgroup analysis showed that NOS score may be the origin of heterogeneity. Conclusions: For patients with sepsis, baseline RDW may be a useful predictor of mortality, patients with increased RDW are more likely to have higher mortality.
Background and objective Gastric cancer (GC) remains a prevalent and preventable disease, yet accurate early diagnostic methods are lacking. Exosome non-coding RNAs (ncRNAs), a type of liquid biopsy, have emerged as promising diagnostic biomarkers for various tumours. This study aimed to identify a serum exosome ncRNA feature for enhancing GC diagnosis. Designs Serum exosomes from patients with GC (n=37) and healthy donors (n=20) were characterised using RNA sequencing, and potential biomarkers for GC were validated through quantitative reverse transcription PCR (qRT-PCR) in both serum exosomes and tissues. A combined diagnostic model was developed using LASSO-logistic regression based on a cohort of 518 GC patients and 460 healthy donors, and its diagnostic performance was evaluated via receiver operating characteristic curves. Results RNA sequencing identified 182 candidate biomarkers for GC, of which 31 were validated as potential biomarkers by qRT-PCR. The combined diagnostic score (cd-score), derived from the expression levels of four long ncRNAs (RP11.443C10.1, CTD-2339L15.3, LINC00567 and DiGeorge syndrome critical region gene (DGCR9)), was found to surpass commonly used biomarkers, such as carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9) and CA72-4, in distinguishing GC patients from healthy donors across training, testing and external validation cohorts, with AUC values of 0.959, 0.942 and 0.949, respectively. Additionally, the cd-score could effectively identify GC patients with negative gastrointestinal tumour biomarkers and those in early-stage. Furthermore, molecular biological assays revealed that knockdown of DGCR9 inhibited GC tumour growth. Conclusions Our proposed serum exosome ncRNA feature provides a promising liquid biopsy approach for enhancing the early diagnosis of GC.
Tumor-derived cytokines and their receptors usually take important roles in the disease progression and prognosis of cancer patients. In this survey, we aimed to detect the expression levels of MIF and CXCR4 in different cell populations of tumor microenvironments and their association with survivals of patients with esophageal squamous cell carcinoma (ESCC).
The levels of liver function tests (LFTs) are often used to assess liver injury and non-liver disease-related mortality. In our study, the relationship between pretreatment serum LFTs and overall survival (OS) was evaluated in esophageal squamous cell carcinoma (ESCC) patients. Our purpose was to investigate the prognostic value of the preoperative alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and gamma glutamyltransferase (GGT) in ESCC patients. A retrospective study was performed in 447 patients with ESCC, and follow-up period was at least 60 months until death. The prognostic significance of serum LFTs were determined by univariate and multivariate Cox hazard models. LFTs including ALT, AST, LSR, GGT, TBA and LDH were analyzed. Serum LSR (HR: 0.592, 95% CI = 0.457–0.768, p < 0.001 and GGT (HR: 1.507, 95% CI = 1.163–1.953, p = 0.002) levels were indicated as significant predictors of OS. The 5-year OS among patients with higher LSR levels was longer compared with those patients with decreased LSR levels, not only in the whole cohort but also in the subgroups stratified by pathological stage (T1–T2 subgroup, T3–T4 subgroup, N0 subgroup and M0 subgroup). We also found that patients with a higher GGT might predict worse OS than patients with a normal GGT, not only in the whole cohort but also in the subgroups stratified by pathological stage (T3–T4 subgroup and N1-N2 subgroup). Both increased levels of LSR and decreased levels of GGT might predict shorter overall survival in ESCC patients. Our findings suggest that serum LSR and GGT levels could be used as a key predictor of survival in patients with ESCC.
Background: To investigate the role of miR-182-5p in the proliferation and invasion of triple-negative breast cancer (TNBC) cells, as well as the underlying mechanism. Methods: qRT-PCR was used to detect the level of miR-182-5p in tissues and cells. CCK-8 assay, flow cytometry, and Transwell assay were performed to detect cell proliferation, apoptosis rate, and invasion, respectively. Pearson correlation analysis was used to determine the correlation between miR-182-5p and its predicted target gene FBXW7, and the target of miR-182-5p was identified by dual-luciferase reporter gene assay. ELISA assay was used to examine the levels of cytokines in the culture supernatant of tumor cells. Western blot analysis was used to detect the expressions of FBXW7, TLR4, and NF-κB) pathways in tumor cells. Results: In MDA-MB-231 and BT-549 cells, downregulation of miR-182-5p significantly inhibited cell proliferation and invasion and promoted tumor cell apoptosis. Pearson correlation analysis showed that miR-182-5p had a negative correlation with FBXW7. Dual-luciferase reporter gene assay showed that miR-182-5p could directly target FBXW7. Further studies showed that FBXW7 overexpression significantly inhibited cell proliferation and invasion and increased the apoptosis rate. Downregulation of miR-182-5p significantly reduced the levels of TNF-α, IL-1 β, IL-6, and IL-18 in the culture supernatant, and decreased the activity of TLR4/NF-κB pathway in tumor cells, while downregulation of FBXW7 significantly inhibited the effect of miR-182-5p on tumor cells. Conclusions: Downregulation of miR-182-5p inhibits TLR4/NF-κB pathway activity by increasing FBXW7 expression, thereby suppressing the proliferation and invasion of TNBC cells.
21 September 2012 in Journal of Translational Medicine
Background: The purpose of this study is to evaluate the predictive significance of preoperative serum level of cytokeratin 19 fragments (Cyfra21-1) and squamous cell carcinoma antigen (SCC-Ag) after complete resection in patients with stage II esophageal squamous cell carcinoma (ESCC).Methods: Between 1995 and 2006, a total of 379 patients in stage II ESCC who underwent complete resection were consecutively recruited. Statistical analyses were applied to test the associations between preoperative serum titers of Cyfra21-1 and SCC-Ag, clinicopathological factors and prognoses.Results: Preoperative high and normal serum level of Cyfra21-1 and SCC-Ag were found in 47.8%, 52.2% and 72.8%, 27.2%, respectively. The 1-, 3-, 5-year overall survival rate for the entire cohort of patients was 95%, 78%, and 56%, respectively. Median overall survival (OS) was 45.3 months longer in patients with low preoperative serum level of Cyfra21-1 (91.9 months) than those with high preoperative serum level of Cyfra21-1 (46.6 months) (P < 0.001). Median OS among patients with SCC-Ag-low level was also longer than those with SCC-Ag-high level (89.7 vs. 63.7 months, P < 0.001), especially for those with stage IIB (P < 0.001). After multivariate analysis, along with pTNM stage, preoperative serum level of Cyfra21-1 and SCC-Ag were independently and significantly predictive factors (P < 0.001, P < 0.001). Furthermore, the five-year survival rate in double-low subset, either-low subset and double-high subset was 100%, 83% and 27%, respectively (P < 0.001).Conclusions: The preoperative serum level of Cyfra21-1 and SCC-Ag are independently significant predictors which negatively affected the survivals of patients with stage II ESCC.