Shu-Qi Li

Identification of differential expressed PE exosomal miRNA in lung adenocarcinoma, tuberculosis, and other benign lesions.

Abstract Pleural effusion (PE) is a common clinical complication of many pulmonary and systemic diseases, including lung cancer and tuberculosis. Nevertheless, there is no clinical effective biomarker to identify the cause of PE. We attempted to investigate differential expressed exosomal miRNAs in PEs of lung adenocarcinoma (APE), tuberculous (TPE), and other benign lesions (NPE) by using deep sequencing and quantitative polymerase chain reaction (qRT-PCR). As a result, 171 differentiated miRNAs were observed in 3 groups of PEs, and 11 significantly differentiated exosomal miRNAs were validated by qRT-PCR. We identified 9 miRNAs, including miR-205-5p, miR-483-5p, miR-375, miR-200c-3p, miR-429, miR-200b-3p, miR-200a-3p, miR-203a-3p, and miR-141-3p which were preferentially represented in exosomes derived from APE when compared with TPE or NPE, while 3 miRNAs, including miR-148a-3p, miR-451a, and miR-150-5p, were differentially expressed between TPE and NPE. These different miRNAs profiles may hold promise as biomarkers for differential diagnosis of PEs with more validation based on larger cohorts.

Exosomes derived from imatinib-resistant chronic myeloid leukemia cells mediate a horizontal transfer of drug-resistant trait by delivering miR-365

&NA; Chronic myeloid leukemia (CML) is a malignant disorder of hematopoietic stem/progenitor cells. Majority of patients can be effectively treated with tyrosine kinase inhibitors (TKIs) such as imatinib, but a portion of patients will develop drug resistance. Accumulated evidences have identified exosomes in cancer as promoters of tumor progression. Herein, we found that exosomes derived from imatinib resistant CML cells can be internalized into sensitive CML cells and confer drug‐resistance traits. We also demonstrated a significant higher level of miR‐365 in exosomes derived from drug‐resistant CML cells compared with those from sensitive ones using microarray and qRT‐PCR. The imatinib sensitive CML cells transfected with pre‐miR‐365 displayed lower chemosensitivity and apoptosis rate compared with controls. We further confirmed that exosomal transfer of miR‐365 induced drug resistance by inhibiting expression of pro‐apoptosis protein in sensitive CML cells. In conclusion, our study reveals that exosomes mediate a horizontal transfer of drug‐resistant trait in chronic myeloid leukemia cell by delivering miR‐365.

Prognostic value of a novel FPR biomarker in patients with surgical stage II and III gastric cancer

Background Inflammation and nutrition are two main causes contributing to progression of gastric cancer (GC), and inflammatory biomarker may be presented as its valuable prognostic factor. Thus, this study was carried out to investigate the prognostic significance of preoperative circulating albumin/fibrinogen ratio (AFR), fibrinogen/pre-Albumin ratio (FPR), fibrinogen (Fib), albumin (Alb) and pre-Albumin (pAlb) in surgical GC. Materials and Methods Three hundred and sixty surgical stage II and III GC patients from June 2011 to December 2013 were enrolled in this retrospective study. X-tile software, Kaplan–Meier curve and Cox regression model were used to evaluate the prognostic role of them. A predictive nomogram was established to predict prognosis of overall survival (OS), and its accuracy was assessed by concordance index (c-index). Results Decreased Alb, pAlb, AFR and elevated FPR were significantly associated with shorter OS. FPR was identified as the most effective prognostic factor to predict 3-year’s OS by time-dependent ROC analysis. A long survival was observed in patients with low level of FPR and the prognosis of stage III FPR-low GC patients undergoing chemotherapy was significantly superior to the patients without the treatment (P=0.002). However, no difference of survival was examined in stage II subgroups stratified by FPR and high FRP of stage III patients with or not the treatment of chemotherapy. C-index of nomogram containing FPR (c-index=0.756) was high in comparison with the nomogram without FPR (c-index =0.748). Conclusion Preoperative FPR might be a feasible prognostic biomarker in surgical stage II and III GC and it could precisely distinguish stage III patients who appeared to obviously benefit from adjuvant chemotherapy. Meanwhile established nomogram based on clinical parameters and FPR could improve its predictive efficacy.

Differential expression of urinary exosomal microRNAs in IgA nephropathy

Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerulonephritis in the world. Reliable biomarkers are required for the non‐invasive diagnosis and monitoring of IgAN. This study aims to investigate the difference in urinary exosomal microRNA (miRNA) expression profiles between patients with IgA nephropathy (IgAN) and healthy controls, which may provide clues to identify novel potential non‐invasive miRNA biomarkers for renal diseases.

Association Between TNF-α -308G/A Polymorphism and Risk of Immune Thrombocytopenia: A Meta-Analysis

OBJECTIVE Previous studies have investigated the association between tumor necrosis factor-alpha (TNF-α) -308G/A polymorphism and risk of immune thrombocytopenia (ITP), but the reported results have been inconsistent. Thus, a systematic meta-analysis was performed to resolve this discrepancy. METHODS Electronic databases and the cited references of the obtained published articles were manually searched. Quality assessment of each study was conducted using the Newcastle-Ottawa Scale (NOS). All case-control studies were used to assess the strength of the association. Statistical analysis was performed using Stata version 12.0. RESULTS Eight high-quality studies, including 947 patients and 1911 controls, were selected for the final meta-analysis. There was no significant association between TNF-α -308G/A polymorphism and ITP in overall and Asian populations. However, a significant positive association was observed between them in the dominant genetic model (AA+AG versus GG) in the Caucasian population (OR = 1.35, 95% confidence interval [CI]: 1.07-1.71, PH = 0.173). CONCLUSIONS Our finding suggested that TNF-α -308G/A might be involved in development of ITP in the Caucasian population, but not in the Asian population. Among Caucasians the A allele (AA+AG) was associated with ITP. However, larger-scale studies are required to confirm our findings.

Circulating fibrinogen to pre-albumin ratio is a promising biomarker for diagnosis of colorectal cancer

Inflammation and nutrition are closely associated with initiation and progression of colorectal cancer (CRC). This study aimed to investigate the diagnostic value of the FAR (FAR = 100*Fibrinogen/Albumin) and FPR (FPR = Fibrinogen/pre‐Albumin) in CRC.

Preoperative circulating FPR and CCF score are promising biomarkers for predicting clinical outcome of stage II–III colorectal cancer patients

Introduction Inflammation and nutrition are considered as two important causes leading to the progression and poor survival of colorectal cancer (CRC). The objective of this study is to investigate the prognostic significance of preoperative albumin-to-fibrinogen ratio (AFR), fibrinogen-to-pre-albumin ratio (FPR), fibrinogen (Fib), albumin (Alb), and pre-albumin (pre-Alb) in CRC individuals. Materials and methods In this study, 3 years’ follow-up was carried out in 702 stage I–III resected CRC patients diagnosed between January 2008 and December 2013. The optimal cutoff points and prognostic values of AFR, FPR, Fib, Alb, pre-Alb, and a novel carcinoembryonic antigen (CEA)-carbohydrate antigen 19-9 (CA199)-FPR (CCF) score were assessed by X-tile software, Kaplan–Meier curve, and Cox regression model. We established the CRC prognostic nomogram, and its predictive efficacy was determined by Harrell’s concordance index (c-index). Results Our results showed that high FPR was obviously correlated with poor survival of CRC patients. The prognostic predictive efficacy of CCF score was superior to FPR, CEA, CA199, CEA-CA199 (CCI), and CEA-FPR (CFI) score. Moreover, stage II–III patients harboring high FPR or elevated CCF (score≥1) could benefit from adjuvant chemotherapy, rather than those with low FPR or CCF (score=0). Additionally, the c-index (0.728) of the nomogram containing CCF score was significantly higher than that (0.626) without it (p<0.01). Conclusion These findings illustrated that FPR and CCF score were promising biomarkers to predict the prognosis of CRC and to classify the stage II–III patients who could benefit from the adjuvant chemotherapy.

Albumin-to-fibrinogen ratio as a promising biomarker to predict clinical outcome of non-small cell lung cancer individuals.

Chronic inflammation is one of the critical causes to promote the initiation and metastasis of solid malignancies including lung cancer (LC). Here, we aimed to investigate the prognostic roles of albumin (Alb)‐to‐fibrinogen (Fib) ratio (AFR), Fib and Alb in LC and to establish a novel effective nomogram combined with AFR. Four hundred twelve LC patients diagnosed between February 2005 and December 2014 were recruited in this prospective study. The prognostic roles of AFR, Fib, Alb, neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR) and monocyte‐to‐lymphocyte ratio (MLR) were identified by X‐tile software, Kaplan–Meier curve, Cox regression model, and time‐dependent ROC. Pretreatment high circulating Fib, low AFR, and Alb were significantly associated with increased risk of death for LC patients, especially for non‐small cell lung cancer (NSCLC) patients in all stages. The area under curves (AUCs) of AFR, Fib, and NLR were higher than them within Alb and PLR for predicting the survival of NSCLC patients. Moreover, we found that clinical outcome of high AFR patient with chemo‐radiotherapy was superior to low AFR patient; overall survival rate of stage II‐III NSCLC patients undergoing chemo‐radiotherapy was significantly lower than the surgical patients with treatment of adjuvant chemo‐radiotherapy(P = 0.001) in low AFR subgroup. On the contrary, clinical outcome of the patients receiving chemo‐radiotherapy was the same to the patients undergoing surgery and adjuvant chemo‐radiotherapy (P = 0.405) in high AFR subgroup. In addition, c‐index of predicted nomogram including AFR (0.717) for NSCLC patients with treatment of chemo‐radiotherapy was higher than that without AFR (0.707). Our findings demonstrated that circulating pretreatment AFR might be a potential biomarker to predict clinical efficacy of surgical resection and adjuvant chemo‐radiotherapy and be a prognostic biomarker for NSCLC individuals.