Xiandong Lin

Preoperative metabolic syndrome and prognosis after radical resection for colorectal cancer: The Fujian prospective investigation of cancer (FIESTA) study.

This prospective study sought to investigate the prediction of preoperative metabolic syndrome and its components for the risk of colorectal cancer (CRC) mortality by analyzing a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. In total, 1,318 CRC patients who received radical resection were consecutively enrolled between January 2000 and December 2008. The median follow‐up time was 58.6 months, with 412 deaths from CRC. The CRC patients with metabolic syndrome had significantly shorter median survival time (MST) than those without (50.9 vs. 170.3 months, p < 0.001). Among four components of metabolic syndrome, hyperglycemia was the strongest predictor and its presence was associated with shorter MST than its absence (44.4 vs. 170.3 months, p < 0.001). Moreover, the complication of metabolic syndrome in CRC patients was associated with a 2.98‐fold increased risk of CRC mortality (hazard ratio [HR] = 2.98, 95% confidence interval [CI]: 2.40–3.69, p < 0.001) after adjusting for confounding factors. The magnitude of this association was especially potentiated in CRC patients with tumor‐node‐metastasis stage I/II (HR = 3.94, 95% CI: 2.65–5.85, p < 0.001), invasion depth T1/T2 (HR = 5.41, 95% CI: 2.54–11.50, p < 0.001), regional lymph node metastasis N0 (HR = 4.06, 95% CI: 2.85‐5.80, p < 0.001) and negative distant metastasis (HR = 3.23, 95% CI: 2.53–4.12, p < 0.001). Further survival tree analysis reinforced the prognostic capability of fasting blood glucose in CRC survival. Our findings convincingly demonstrated that preoperative metabolic syndrome, especially hyperglycemia, was a robust predictor for CRC mortality, and the protection was more obvious in patients with Stage I/II.

Preoperative blood-routine markers and prognosis of esophageal squamous cell carcinoma: The Fujian prospective investigation of cancer (FIESTA) study.

This prospective study was designed to investigate the prognosis of preoperative blood-routine markers for esophageal cancer mortality by using data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. Patients who received three-field lymphadenectomy for esophageal cancer between 2000 and 2010 were enrolled. Of 2535 patients with complete survival data, esophageal squamous cell carcinoma (ESCC) accounted for 94.5% (n = 2396). Here, only ESCC patients were analyzed, with the median follow-up time of 38.2 months (range: 0.5 to 180 months). Of 10 blood-routine markers evaluated, platelet count and red cell distribution width (RDW) were two significant predictors for ESCC mortality in men (adjusted hazard ratio or HR = 1.25 and 0.84, 95% confidence interval or CI: 1.08-1.22 and 0.75-0.93, P < 0.001 and P = 0.001, respectively), while in women only lymphocyte showed marginal significance. Based on individual results, a new derivate calculated as platelet count to RDW ratio (PRR) was created, and it was superior over other widely-evaluated derivates in men after adjustment (HR = 1.21, 95% CI: 1.13-1.30, P < 0.001), while there was no observable significance in women. In further stratified analyses, the prognosis of PRR for ESCC mortality was reinforced in men with tumor-node-metastasis stage III (HR, 95% CI, P: 1.18, 1.09-1.28, 0.001), invasion depth T3-T4 (1.17, 1.08-1.26, <0.001) or positive lymph node metastasis (1.37, 1.18-1.59, <0.001). Taken together, we created a new derivate PRR that was proven to be superior over other blood-routine markers and exhibited strong prognostic capability for ESCC mortality in Chinese men.

SNHG8 is identified as a key regulator of epstein-barr virus(EBV)-associated gastric cancer by an integrative analysis of lncRNA and mRNA expression

The Epstein–Barr virus (EBV) is associated with a variety of cancers, including gastric cancer, which has one of the highest mortality rates of all human cancers. Long non-coding RNAs (lncRNAs) have been suggested to have important causal roles in gastric cancer. However, the interaction between lncRNAs and EBV has not yet been studied. To this end, we sequenced 11,311 lncRNAs and 144,826 protein-coding transcripts from four types of tissue: one non-EBV-infected gastric carcinoma (EBVnGC) and its adjacent normal tissue, and one EBV-associated gastric carcinoma (EBVaGC) and its adjacent normal tissue. Five lncRNAs showed EBVaGC-specific expression; of those, one (SNHG8) was validated using real-time PCR in an independent cohort with 88 paired gastric cancer and adjacent tissue samples. To explore the functions of SNHG8, we identified its mRNA targets on the lncRNA–mRNA co-expression network of the Illumina Body Map, which contains the RNA sequencing data of mRNAs and lncRNAs from 16 normal human tissues. SNHG8 lncRNA was found to affect several gastric cancer-specific pathways and target genes of EBV. Our results reveal the intertwined tumorigenesis mechanisms of lncRNA and EBV and identify SNHG8 as a highly possible candidate biomarker and drug target of gastric cancer.

Elevated preoperative neutrophil-to-lymphocyte ratio can predict poor survival in early stage gastric cancer patients receiving radical gastrectomy: The Fujian prospective investigation of cancer (FIESTA) study

Aims: This cohort study was conducted to evaluate the prognostic impact of blood-routine parameters before radical gastrectomy on gastric cancer mortality. Methods: Total 3012 patients with gastric cancer were consecutively enrolled from a mono-center between 2000 and 2010, and the latest follow-up was completed in 2015. Results: The median follow-up time was 44.05 months. Finally, 1331 out of 3012 gastric cancer patients died from gastric cancer. Per standard deviation increment in neutrophil (hazard ratio or HR=1.08, P<0.001), white blood cell count (HR=1.07, P=0.001), neutrophil-to-lymphocyte ratio or NLR (HR=1.08, P<0.001) and platelet-to-lymphocyte ratio (HR=1.08, P<0.001) was significantly associated with an increased risk of gastric cancer mortality, while that in lymphocyte (HR=0.69, P<0.001), hemoglobin (HR=0.82, P<0.001) and lymphocyte-to-monocyte ratio (HR=0.68, P<0.001) was associated with a reduced risk. Survival tree analysis indicated that in patients with TNM stage I/II, the contrasts of NLR>2.61 with ≤2.61 and NLR>1.87 with ≤1.87 were respectively associated with a 5.21-fold (P=0.004) and 2.36-fold (P=0.001) increased risk of gastric cancer mortality. The effect-size magnitude of NLR was further potentiated in patients with invasion depth T1/T2 (HR=1.73, P=0.001), regional lymph node metastasis N0 (HR=1.60, P<0.001), TNM stage I/II (HR=1.36, P=0.009) and tumor size ≤ 4.5 cm (HR=1.17, P<0.001). Conclusions: Our findings consolidated the prognostic impact of preoperative NLR on gastric mortality, and demonstrated that elevated preoperative NLR was a robust indicator of poor survival in patients at early stage.

Preoperative Metabolic Syndrome Is Predictive of Significant Gastric Cancer Mortality after Gastrectomy: The Fujian Prospective Investigation of Cancer (FIESTA) Study

Metabolic syndrome (MetS) has been shown to be associated with an increased risk of gastric cancer. However, the impact of MetS on gastric cancer mortality remains largely unknown. Here, we prospectively examined the prediction of preoperative MetS for gastric cancer mortality by analyzing a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. This study was conducted among 3012 patients with gastric cancer who received radical gastrectomy between 2000 and 2010. The latest follow-up was completed in 2015. Blood/tissue specimens, demographic and clinicopathologic characteristics were collected at baseline. During 15-year follow-up, 1331 of 3012 patients died of gastric cancer. The median survival time (MST) of patients with MetS was 31.3 months, which was significantly shorter than that of MetS-free patients (157.1 months). The coexistence of MetS before surgery was associated with a 2.3-fold increased risk for gastric cancer mortality (P < 0.001). The multivariate-adjusted hazard ratios (HRs) were increased with invasion depth T1/T2 (HR = 2.78, P < 0.001), regional lymph node metastasis N0 (HR = 2.65, P < 0.001), positive distant metastasis (HR = 2.53, P < 0.001), TNM stage I/II (HR = 3.00, P < 0.001), intestinal type (HR = 2.96, P < 0.001), negative tumor embolus (HR = 2.34, P < 0.001), and tumor size ≤ 4.5 cm (HR = 2.49, P < 0.001). Further survival tree analysis confirmed the top splitting role of TNM stage, followed by MetS or hyperglycemia with remarkable discrimination ability. In this large cohort study, preoperative MetS, especially hyperglycemia, was predictive of significant gastric cancer mortality in patients with radical gastrectomy, especially for early stage of gastric cancer.

The elevated preoperative fasting blood glucose predicts a poor prognosis in patients with esophageal squamous cell carcinoma: The Fujian prospective investigation of cancer (FIESTA) study

Diabetes as a latent risk factor for cancer has been extensively investigated, while its postoperative prognosis for esophageal cancer is rarely reported. We therefore sought to assess whether the elevated fasting blood glucose before surgery was associated with poor survival in esophageal cancer patients by eliciting a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. Over 15-year follow-up, 2535 patients receiving three-field lymphadenectomy were assessable. Only patients with esophageal squamous cell carcinoma (ESCC) (n=2396) were analyzed due to the lower prevalence of the other histological types. In ESCC patients, the follow-up duration ranged from 0.5 to 180 months (median 38.2 months). The median survival time (MST) was remarkably shorter in males than in females (80.7 vs. 180+ months, Log-rank test: P<0.001). In males, the survival was worse in patients with diabetes than those without (MST: 27.9 vs. 111.1 months, Log-rank test: P<0.001). In females, the survivor was improved in patients with diabetes (MST: 71.5 months), but was still worse than patients without diabetes (MST: 180+ months, Log-rank test: P<0.001). The overall multivariate hazard ratio for per unit increment in fasting blood glucose was 1.11 (95% confidence interval or CI: 1.09-1.14, P<0.001) and 1.08 (95% CI: 1.03-1.13, P=0.002) in males and females, respectively. Further survival tree analysis consolidated the discrimination ability of fasting blood glucose for the survival of ESCC patients. Taken together, our findings convincingly demonstrated that the elevated preoperative fasting blood glucose can predict poor survival of ESCC patients, especially in males.

APEX Nuclease (Multifunctional DNA Repair Enzyme) 1 Gene Asp148Glu Polymorphism and Cancer Risk: A Meta-Analysis Involving 58 Articles and 48903 Participants

Background Polymorphisms in the APEX nuclease (multifunctional DNA repair enzyme) 1 gene (APEX1) may be involved in the carcinogenesis by affecting DNA repair. We aimed to summarize available data on the association of the APEX1 Asp148Glu (rs1130409) polymorphism with risk of multiple types of cancer via a meta-analysis. Methods and Results In total, 58 qualified articles including 22,398 cancer patients and 26,505 controls were analyzed, and the data were extracted independently by two investigators. Analyses of the full data set indicated a marginally significant association of the APEX1 Asp148Glu polymorphism with cancer risk under allelic (odds ratio (OR)=1.05; 95% confidence interval (95% CI): 0.99-1.11; P=0.071), dominant (OR=1.09; 95% CI: 1.01-1.17; P=0.028), and heterozygous genotypic (OR=1.08; 95% CI: 1.01-1.16; P=0.026) models, with significant heterogeneity and publication bias. In subgroup analyses by cancer type, with a Bonferroni corrected alpha of 0.05/6, significant association was observed for gastric cancer under both dominant (OR=1.74; 95% CI: 1.2-2.51; P=0.003) and heterozygous genotypic (OR=1.66; 95% CI: 1.2-2.31; P=0.002) models. In subgroup analysis by ethnicity, risk estimates were augmented in Caucasians, especially under dominant (OR=1.11; 95% CI: 1.0-1.24; P=0.049) and heterozygous genotypic (OR=1.11; 95% CI: 0.99-1.24; P=0.063) models. By study design, there were no significant differences between population-based and hospital-based studies. In subgroup analysis by sample size, risk estimates were remarkably overestimated in small studies, and no significance was reached in large studies except under the heterozygous genotypic model (OR=1.23; 95% CI: 1.06-1.43; P=0.006, significant at a Bonferroni corrected alpha of 0.05/2). By quality score, the risk estimates, albeit nonsignificant, were higher in low-quality studies than in high-quality studies. Further meta-regression analyses failed to identify any contributory confounders for the associated risk estimates. Conclusions Our findings suggest that APEX1 Asp148Glu polymorphism might be a genetic risk factor for the development of gastric cancer. Further investigations on large populations are warranted.

Transcriptome-wide piRNA profiling in human brains of Alzheimer's disease

Discovered in the brains of multiple animal species, piRNAs may contribute to the pathogenesis of neuropsychiatric illnesses. The present study aimed to identify brain piRNAs across transcriptome that are associated with Alzheimers disease (AD). Prefrontal cortical tissues of 6 AD cases and 6 controls were examined for piRNA expression levels using an Arraystar HG19 piRNA array (containing 23,677 piRNAs) and genotyped for 17 genome-wide significant and replicated risk SNPs. We examined whether piRNAs are expressed differently between AD cases and controls and explored the potential regulatory effects of risk SNPs on piRNA expression levels. We identified a total of 9453 piRNAs in human brains, with 103 nominally (p < 0.05) differentially (>1.5 fold) expressed in AD cases versus controls and most of the 103 piRNAs nominally correlated with genome-wide significant risk SNPs. We conclude that piRNAs are abundant in human brains and may represent risk biomarkers of AD.

The monocyte to red blood cell count ratio is a strong predictor of postoperative survival in colorectal cancer patients: The Fujian prospective investigation of cancer (FIESTA) study

Background and Aims: We sought to evaluate the prognosis of preoperative blood routine parameters for the mortality of colorectal cancer patients after surgery by eliciting a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. Methods: 1318 colorectal cancer patients with completed survival data were enrolled between 2000 and 2008. Effect-size estimates are expressed as hazard ratio (HR) and 95% confidence interval (CI). Results: The median follow-up time was 58.6 months. Elevated levels of neutrophil (adjusted HR, 95% CI, P: 1.22, 1.06-1.41, 0.006) and monocyte (1.32, 1.06-1.65, 0.013) were significantly associated with an increased risk of colorectal cancer mortality, whereas that of lymphocyte (0.60, 0.44-0.82, 0.001) and red blood cell count (0.20, 0.09-0.43, <0.001) were significantly associated with a reduced risk. Additionally, remarkable significance was reached for the neutrophil-to-lymphocyte ratio (1.12, 1.06-1.19, <0.001) and lymphocyte-to-monocyte ratio (0.60, 0.46-0.79, <0.001). Based on individual effect-estimates, a new derivate, monocyte to red blood cell count ratio namely MRR was created, and its association with colorectal cancer mortality was strikingly significant (1.48, 1.18-1.85, 0.001). Notably, elevated MRR was significantly associated with the mortality of early stage colorectal cancer, especially in patients with stage I-II (1.63, 1.04-2.56, 0.034), invasion depth T1-T2 (2.85, 1.45-5.61, 0.002), regional lymph node metastasis N0 (1.89, 1.29-2.77, 0.001) and tumor size ≤ 4.5 cm (1.84, 1.25-2.70, 0.002). Conclusions: We created a new derivate MRR, which was superior over classic blood routine derivates, and importantly the MRR exhibited a stronger ability in predicting poor prognosis of colorectal cancer, especially at the early stage.

Analysis of Preoperative Metabolic Risk Factors Affecting the Prognosis of Patients with Esophageal Squamous Cell Carcinoma: The Fujian Prospective Investigation of Cancer (FIESTA) Study

Some metabolic factors have been shown to be associated with an increased risk of esophageal cancer; however the association with its prognosis is rarely reported. Here, we assessed the prediction of preoperative metabolic syndrome and its single components for esophageal cancer mortality by analyzing a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. Between 2000 and 2010, patients who underwent three-field lymphadenectomy were eligible for inclusion. Blood/tissue specimens, demographic and clinicopathologic data were collected at baseline. Metabolic syndrome is defined by the criteria proposed by Chinese Diabetes Society. In this study, analysis was restricted to esophageal squamous cell carcinoma (ESCC) due to the limited number of other histological types. The median follow-up in 2396 ESCC patients (males/females: 1822/574) was 38.2 months (range, 0.5–180 months). The multivariate-adjusted hazard ratio (HR) of metabolic syndrome for ESCC mortality was statistically significant in males (HR, 95% confidence interval, P: 1.45, 1.14–1.83, 0.002), but not in females (1.46, 0.92–2.31, 0.107). For single metabolic components, the multivariate-adjusted HRs were significant for hyperglycemia (1.98, 1.68–2.33, < 0.001) and dyslipidemia (1.41, 1.20–1.65, < 0.001) in males and for hyperglycemia (1.76, 1.23–2.51, < 0.001) in females, independent of clinicopathologic characteristics and obesity. In tree-structured survival analysis, the top splitting factor in both genders was tumor-node-metastasis stage, followed by regional lymph node metastasis. Taken together, our findings demonstrate that preoperative metabolic syndrome was a significant independent predictor of ESCC mortality in males, and this effect was largely mediated by glyeolipid metabolism disorder.