High expression of the long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) in whole blood has been reported in colorectal cancer patients; however, its’ clinical significance and origin are unclear. We evaluated the diagnostic and prognostic value, and origin of whole blood NEAT1 in colorectal cancer. Expression of NEAT1 variants, NEAT1_v1 and NEAT1_v2 were determined using real-time quantitative PCR. The diagnostic value of whole blood NEAT1 expression was evaluated in test (n = 60) and validation (n = 200) cohorts of colorectal cancer patients and normal controls (NCs). To identify the origin of NEAT1, its expression was analyzed in blood, matched primary tumor tissues, para-tumor tissues, metastatic tissues, and also immune cells from patients or NCs. Function of NEAT1 in colorectal cell lines was also assessed. The correlation of NEAT1 expression with clinical outcomes was assessed in 191 patients. Whole blood NEAT1 expression was significantly higher in colorectal cancer patients than in NCs. NEAT1_v1 and NEAT1_v2 expression were highly accurate in distinguishing colorectal cancer patients from NCs (area under the curve: 0.787 and 0.871, respectively). Knockdown of NEAT1_v1 in vitro could inhibit cell invasion and proliferation, while knockdown of NEAT1_v2 promoted cell growth. However, whole blood expression was not correlated with matched tissues. An elevated expression was seen in neutrophils from CRC patients. Furthermore, high expression of NEAT1_v1 was correlated with worse overall survival. In contrast, high expression of NEAT1_v2 alone was correlated with better overall survival. Whole blood NEAT1 expression is a novel diagnostic and prognostic biomarker of overall survival in colorectal cancer. Elevated NEAT1 may derive from neutrophils.

Recent evidence indicates that inflammatory parameters could be useful to predict metastasis from colorectal cancer. However, their roles in predicting chemotherapy response and prognosis in patients with synchronous colorectal liver metastasis (CLM) are unknown. The clinical data and baseline laboratory parameters of 55 patients with synchronous CLM were retrospectively reviewed. All patients underwent palliative resection of the primary tumor and oxaliplatin-based chemotherapy. Two indices of systemic inflammation were reviewed—neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR)—preoperatively and before the second cycle of chemotherapy. Associations between prognostic variables and tumor response, progression, and survival were investigated. NLR < 4 and PLR < 150 were correlated with better disease control (p = 0.024 and 0.026, respectively). In univariate analysis, elevated NLR and PLR were significant prognostic factors for poor overall survival (OS) and progression-free survival (PFS). In multivariate analysis, PLR (p = 0.027), age (p = 0.018), resection of liver metastases (p = 0.017), and lactate dehydrogenase level (p = 0.011) were independent predictors of PFS, while resection of liver metastases was the only independent predictor of OS (p = 0.002). In addition, when patients were divided into groups according to changes in NLR and/or PLR, reduced NLR and PLR were associated with improved disease control (p = 0.038 and 0.025, respectively). Normalization of NLR also was associated with improved PFS. NLR and PLR are potentially useful clinical biomarkers to predict chemotherapy response in patients with synchronous CLM. PLR also may be useful to predict PFS in these patients.

Temporary diverting stoma might be a protective factor for the prevention of anastomotic leakage (AL) after anterior resection. Its role in leakage recovery is unknown. This study aimed to evaluate the effect of temporary diverting stoma on anastomotic leakage severity and recovery. We analyzed 323 patients who underwent anterior resection for rectal cancer and developed anastomotic leakage, in which 44 had temporary diverting stoma. Association between diverting stoma and occurrence of anastomotic leakage, recovery time, length of hospital stay, overall costs, local and distant relapse-free survival were further studied. In non-severe AL group, temporary diverting stoma improved leakage recovery by 4 days (mean: 20.7 days vs. 16.1 days, p = 0.031), especially in patients who did not receive neoadjuvant treatment (mean time: 20.9 days vs. 14.4 days, p = 0.016). However, it did not delay the occurrence of anastomotic leakage. Moreover, no significant difference was found in the overall length of hospital stay and costs among patients with versus without a diverting stoma. In severe AL group, however, no difference was detected. The advantage of shortened leakage recovery did not reduce the local and distant relapse-free survival. In conclusion, our findings indicated the recovery benefit from diverting stoma in patients with anterior resection.

Circular RNA (circRNA) plays an essential role in the development and progression of various cancers. However, the functions and mechanisms of circRNA in colorectal liver metastasis have not been fully elucidated. We performed circRNA microarray analysis to screen differentially expressed circRNA in the pathology of colorectal liver metastasis. Quantitative real‐time PCR was used to detect the expression of hsa_circ_102049 (circ102049) in colorectal cancer (CRC) samples. CRC cells were transfected with circ102049 overexpression vector or small interfering (si)RNA to assess the effects of circ102049 in vitro. Bioinformatics analysis, fluorescence in situ hybridization, RNA immunoprecipitation, RNA pull‐down and luciferase reporter assays were conducted to confirm the relationship of circ102049, miR‐761, miR‐192‐3p and FRAS1. The mechanism by which circ102049 recruits and distributes DGCR8 protein in the cytoplasm was also investigated. We found that circ102049 was highly expressed in primary CRC tumors with liver metastasis and closely correlated with the prognosis of patients with CRC. Circ102049 significantly enhanced the adhesion, migration and invasion abilities of CRC cells, and promoted CRC progression via a micro (mi)R‐761/miR‐192‐3p‐FRAS1‐dependent mechanism. Notably, due to the distribution of DGCR8 protein, circ102049 may also indirectly reduce the levels of mature miR‐761 and miR‐192‐3p in the cytoplasm. In addition, the role of circ102049 in promoting colorectal liver metastasis was confirmed in vivo. Our findings provide new evidence that circ102049 may be a potential prognostic factor in CRC, and that the circ102049‐miR‐761/miR‐192‐3p–FRAS1 axis may be an anti‐metastatic target for CRC patients.

Innate immunity provides first line of defense against viral infections. The interactions between hosts and influenza A virus and the response of host innate immunity to viral infection are critical determinants for the pathogenicity or virulence of influenza A viruses. This study was designed to investigate global changes of gene expression and detailed responses of innate immune systems in human and avian hosts during the course of infection with various subtypes of influenza A viruses, using collected and self-generated transcriptome sequencing data from human bronchial epithelial (HBE), human tracheobronchial epithelial (HTBE), and A549 cells infected with influenza A virus subtypes, namely H1N1, H3N2, H5N1 HALo mutant, and H7N9, and from ileum and lung of chicken and quail infected with H5N1, or H5N2. We examined the induction of various cytokines and chemokines in human hosts infected with different subtypes of influenza A viruses. Type I and III interferons were found to be differentially induced with each subtype. H3N2 caused abrupt and the strongest response of IFN-β and IFN-λ, followed by H1N1 (though much weaker), whereas H5N1 HALo mutant and H7N9 induced very minor change in expression of type I and III interferons. Similarly, differential responses of other innate immunity-related genes were observed, including TMEM173, MX1, OASL, IFI6, IFITs, IFITMs, and various chemokine genes like CCL5, CX3CL1, and chemokine (C-X-C motif) ligands, SOCS (suppressors of cytokine signaling) genes. Third, the replication kinetics of H1N1, H3N2, H5N1 HALo mutant and H7N9 subtypes were analyzed, H5N1 HALo mutant was found to have the highest viral replication rate, followed by H3N2, and H1N1, while H7N9 had a rate similar to that of H1N1 or H3N2 though in different host cell type. Our study illustrated the differential responses of innate immunity to infections of different subtypes of influenza A viruses. We found the influenza viruses which induced stronger innate immune responses replicate slower than those induces weaker innate immune responses. Our study provides important insight into links between the differential innate immune responses from hosts and the pathogenicity/ virulence of different subtypes of influenza A viruses.

Colon cancer is a frequently occurring primary malignant tumor. Chemotherapy can reduce the risk of local and distant relapse. Therefore, it is very important to find new biomarkers that can predict chemoresistance and help in individuate treatment decision. Retrospective analysis of 126 patients, who were treated at our department between June 2010 and December 2014. In this study, we examined the expression levels of 1200 human miRNAs in colon cancer tissues, using laser capture microdissection and microRNA profiling arrays. A validation study was done to corroborate a subset of the results, including expression levels of miR-4299, miR-196b, miR-324-5p, miR-455-3p and miR-939, through analyzing stage IV colon adenocarcinoma tissues (not responding and responding to the chemotherapy) with laser capture microdissection and quantitative real-time PCR. We analyze the relationship between the expression levels of these miRNAs and the survival rate of colon cancer patients by Kaplan–Meier method. We found that miR-4299 and -196b have significant diagnostic value in chemoresistant colon cancer. MiR-4299 yielded an AUC (the areas under the ROC curve) of 0.810 and miR-196b yielded an AUC of 0.726 in discriminating chemoresistant colon cancer from controls. Combined with ROC analyses of these 2 miRNAs revealed an elevated AUC of 0.877 with 71.4 % sensitivity and 95.5 % specificity in discriminating chemoresistant colon cancer. The low level of miR-4299 expression and the high level of -196b expression are significantly correlated with better survival of colon cancer patients. These data suggest that miR-4299 and -196b have strong potential as novel biomarkers for chemoresistance detection of colon cancer.