Effects of vascular endothelial growth factor expression on pathological characteristics and prognosis of osteosarcoma

Vascular endothelial growth factor (VEGF) has been linked with tumor invasion and metastasis. However, the role of VEGF expression in osteosarcoma remains controversial. By searching the PubMed, Embase, and Google Scholar databases, we conducted a meta-analysis to evaluate the pathological and prognostic significance of VEGF in osteosarcoma. Studies were pooled, and the odds ratio (OR) and its corresponding 95 % confidence interval (CI) were calculated. Nine relevant articles were included in this meta-analysis study. We performed pooled analysis with available data on the association between VEGF expression and age, gender, tumor stages IIB–III versus I–IIA, tumor recurrence, response to chemotherapy, and tumor metastasis. Our results revealed that VEGF expression might be closely associated with metastasis of osteosarcoma (OR 4.74, 95 % CI 2.53–8.87, P < 0.001). Furthermore, our findings also demonstrated that patients with grade IIB–III osteosarcoma showed a higher frequency of VEGF expression than those with grade I–IIA osteosarcoma (OR 5.33, 95 % CI 2.03–13.98, P = 0.001). We failed to find the association between VEGF expression and age (OR 0.82, 95 % CI 0.44–1.53, P = 0.539), gender (OR 1.33, 95 % CI 0.52–3.42, P = 0.553), tumor recurrence (OR 1.47, 95 % CI 0.56–3.86, P = 0.429), and response to chemotherapy (OR 1.26, 95 % CI 0.14–11.72, P = 0.839). In conclusion, VEGF is related to the grade and metastasis of osteosarcoma. It may play a significant role in clinical guidelines for the treatment and prognostic evaluation.     

Pathological and prognostic significance of matrix metalloproteinase-2 expression in ovarian cancer: a meta-analysis

Matrix metalloproteinase-2 (MMP-2) has been linked with tumor invasion and metastasis. However, the role of MMP-2 expression in ovarian cancer remains controversial. By searching the PubMed, Embase, Wanfang, and China National Knowledge Infrastructure databases, we conducted a meta-analysis to evaluate the pathological and prognostic significance of MMP-2 in ovarian cancer. Studies were pooled, and the odds ratio (OR) and its corresponding 95 % confidence interval (CI) were calculated. Version 11.0 STATA software was used for statistical analysis. Twenty-seven relevant articles were included for this meta-analysis study. The expression of MMP-2 in cancer tissue was significantly higher than that in benign or normal ovarian tissue [cancer vs. benign, OR 10.09 (95 % CI 6.95–14.64); P < 0.001; cancer vs. normal, OR 30.48 (95 % CI 17.19–54.05); P < 0.001; benign vs. normal, OR 1.88 (95 % CI 1.08–3.29); P = 0.025]. The expression of MMP-2 in stage III–IV or lymph node metastasis was significantly higher than that in stage I–II or that without metastasis, respectively [OR 5.83 (95 % CI 4.32–7.85); P < 0.001; OR 7.20 (95 % CI 4.75–10.91); P < 0.001]. MMP-2 was associated with histological types and grade of ovarian cancer [serous vs. mucinous, OR 1.67 (95 % CI 1.17–2.39); P = 0.004; grade 3 vs. 1, 2, OR 3.23 (95 % CI 2.29–4.55); P < 0.001]. However, the age of patients was not associated with MMP-2 expression [OR 1.25 (95 % CI 0.61–2.58); P = 0.546]. In conclusion, MMP-2 is related to the malignant degree, FIGO stage, histological types and grade, and lymph node metastasis of ovarian cancer. It may play a significant role in clinical guidelines for the treatment and prognostic evaluation.     

Interleukin-28B TT genotype is frequently found in patients with hepatitis C virus cirrhosis but does not influence hepatocarcinogenesis

Persistent hepatitis C virus (HCV) infection is associated with progressive hepatic fibrosis and ultimately hepatocellular carcinoma. The interleukin-28B (IL28B) rs12979860 polymorphism is associated with fibrosis progression in chronic HCV infection. IL28B encodes interferon-λ, which has both antiviral and anti-proliferative properties. This study aimed to determine whether IL28B rs12979860 polymorphism is also associated with development of hepatocellular carcinoma both in chronic HCV infection and in non-viral-related cirrhosis. Real-time polymerase chain reaction and melting curve analyses were used to genotype 311 patients who underwent liver transplantation for HCV cirrhosis (n = 202) or alcoholic cirrhosis (n = 109). HCV patients were older (p = 0.012) and less likely males (p < 0.001) than patients with alcoholic cirrhosis. IL28B rs12979860 TT genotype [OR 6.08, 95 % CI 2.11–17.53; p < 0.001] and T allele carriage (CT + TT; OR 2.3, CI 95 % 1.42–3.72; p = 0.001) were more frequent among HCV patients and, among them, more common in patients infected with HCV genotype 1 (CT + TT; OR 1.79, CI 95 % 1.03–3.09; p = 0.009). Incidence of hepatocellular carcinoma was higher in HCV cirrhosis (OR 2.7, CI 95 % 1.5–4.7; p < 0.001), with no differences according to HCV genotype. IL28B genotype distribution was similar among patients with or without hepatocellular carcinoma, in both HCV patients regardless viral genotype (p = 0.84) and alcoholic patients (p = 0.91). Multivariate analysis showed that older age (OR 1.06, CI 95 % 1.02–1.1; p = 0.003) and male gender (OR 2.49, CI 95 % 1.24–5; p = 0.01) were independent risk factors for hepatocellular carcinoma in HCV patients. In summary, the current study did not find a significant association between IL28B rs12979860 polymorphism and hepatocarcinogenesis.     

Clinicopathological and prognostic significance of Nestin expression in patients with non-small cell lung cancer: a systematic review and meta-analysis

Latest evidence indicates that Nestin expression may be associated with the high malignancy and poor prognosis of non-small cell lung cancer (NSCLC), but a relevant consensus has not been reached until now. Therefore, we conducted this meta-analysis to evaluate the clinicopathological and prognostic significance of Nestin expression in patients with NSCLC. We searched PubMed, EMBASE and the Web of Science for eligible full-text articles. Odds ratio (OR) and hazard ratio (HR) with 95 % confidence interval (95 % CI) severed as the summarized statistics. Q-test and I ²-statistic were applied to evaluate the heterogeneity, and sensitivity analysis was conducted for adjustments. Publication bias was detected by Begg’s test and Egger’s test. Finally, eight eligible articles with 834 NSCLC cases were included. Nestin expression was found to be significantly associated with the unfavorable outcomes of differentiation degree (OR: 2.47; 95 % CI 1.61–3.79; P < 0.001), lymphatic metastasis (OR: 2.45; 95 % CI 1.41–4.25; P = 0.001), TNM stage (OR: 1.73; 95 % CI 1.07–2.79; P = 0.025) and tumor size (OR: 2.68; 95 % CI 1.20–5.98; P = 0.016), but not associated with gender, age, smoking status and NSCLC subtypes. Nestin expression could significantly predict the lower overall survival of NSCLC (HR: 2.41; 95 % CI 1.72–3.38; P < 0.001). The prognostic value of Nestin remained statistically reliable in the subgroups stratified by statistical analysis, patients’ origins and follow-up periods, but not significant in patients with squamous cell carcinoma. In conclusion, Nestin expression may be an independent predictor for the poor prognosis and clinicopathological characteristics of NSCLC. Further studies are necessary to validate our discoveries.     

The effects of <Emphasis Type="Italic">SP110</Emphasis>’s associated genes on fresh cavitary pulmonary tuberculosis in Han Chinese population

SP110 is a promising anti-Mycobacterium tuberculosis (MTB) gene. To investigate the effects of SP110 and its associated genes, i.e., MYBBP1A and RELA, on pathological progression of MTB infection, an association study with 424 patients of fresh pulmonary tuberculosis (PTB) and 424 healthy controls was performed. Moreover, classification and regression tree and multifactor dimensionality reduction were employed to explore the effects of gene–gene interactions on cavitary PTB. The results indicated that both the heterozygous genotype GC and homozygous genotype CC in rs3809849 had significant effects on the risk of PTB (OR 1.42, 95 % CI 1.06–1.92, p 0.019; OR 1.55, 95 % CI 1.04–2.33, p = 0.033, respectively), and heterozygous genotype CT in rs9061 also had similar effects (OR 1.43, 95 % CI 1.07–1.90, p = 0.014). The rs3809849 and rs9905742 in MYBBP1A were also significantly associated with cavitary PTB (p = 0.00046 and 0.039, respectively), while rs9061 in SP110 had no such association (p = 0.06931) except its significant association with non-cavitary PTB (p = 0.0093). The interaction of MYBBP1A and RELA had significant effect on cavitary PTB (OR 4.24, 95 % CI 1.44–12.49, p = 0.005). These suggest that MYBBP1A instead of SP110 may be a genetic risk factor for cavitary PTB and play important effects on its whole progress.     

Evaluation of glycemic control in patients with type 2 diabetes mellitus in Chinese communities: a cross-sectional study

This study aimed to evaluate the glycemic levels in Chinese patients with type 2 diabetes mellitus (T2DM) and to explore the factors related to the results of glycemic control. A total of 2454 T2DM patients from 11 communities were examined for glycosylated hemoglobin levels and glycemic control options. Potential factors related to the results of glycemic control were analyzed using logistic regression. Of all the patients, 55.3 % achieved the glycemic control target of HbA1c < 7 %. Multivariate analysis showed that male sex (OR 1.345, 95 % CI 1.022–1.769; P = 0.034), higher levels of fasting blood glucose (OR 1.954, 95 % CI 1.778–2.147; P < 0.001), and low-density lipoprotein cholesterol (OR 1.181, 95 % CI 1.020–1.367; P = 0.026) were significantly associated with poor glycemic control. The complexity of antidiabetics was also associated with poor glycemic control (P < 0.05). Compared to diet and exercise, insulin injection was most strongly associated with poor glycemic control (OR 6.210, 95 % CI 4.054–9.514; P < 0.001). Male patients with higher levels of total cholesterol, lower levels of high-density lipoprotein cholesterol, or longer diabetic durations showed poor glycemic control, which was not found in female patients. Glycemic control was not satisfactory in T2DM patients of Nanjing communities. Various factors are associated with poor results of glycemic control.     

The <Emphasis Type="Italic">NLRP3</Emphasis> and <Emphasis Type="Italic">CASP1</Emphasis> gene polymorphisms are associated with developing of acute coronary syndrome: a case-control study

The protein products of NLRP3 and CASP1 genes are involved in the cleavage of pro-IL-1B and pro-IL-18 leading to the active cytokines, which play an important role in the development of the acute coronary syndrome (ACS). The aim of the present study was to evaluate whether NLRP3 and CASP1 gene polymorphisms are biomarkers of ACS susceptibility in Mexican population. Two polymorphisms of the CASP1 gene [G+7/in6A (rs501192) and A10370-G Exon-6 (rs580253)] and one of the NLRP3 gene [UTR′3 G37562-C (rs10754558)] were genotyped by 5′ exonuclease TaqMan assays in a group of 617 patients with ACS and 609 control individuals. Under recessive model, the CASP1 G+7/in6A polymorphism was associated with an increased risk of developing ACS when compared to healthy controls (OR = 1.76, 95% CI 1.08–2.86, P _Res  = 0.022). In the same way, under recessive model, the CASP1 A10370-G was associated with increased risk of ACS (OR = 1.75, 95% CI 1.07–2.85, P _Res  = 0.025). Moreover, under co-dominant, dominant, over-dominant, and additive models, the NLRP3 UTR′3 G37562-C was associated with a decreased risk of ACS (OR = 0.45, 95%CI 0.22–0.92, P _Co-dom  = 0.006; OR = 0.61, 95%CI 0.44–0.84, P _Dom  = 0.002; OR = 0.67, 95%CI 0.48–0.94, P _Over-dom  = 0.02; and OR = 0.65, 95%CI 0.50–0.94, P _Add  = 0.02, respectively). In summary, this study demonstrates that the G+7/in6A and A10370-G polymorphisms of the CASP1 gene are associated with increased risk of developing ACS, whereas the UTR′3 G37562-C polymorphism of the NLRP3 gene is associated with a decreased risk of developing ACS in Mexican population.     

Prognostic and clinicopathological significance of PD-L1 in patients with renal cell carcinoma: a meta-analysis based on 1863 individuals

The prognostic significance of PD-L1 in renal cell carcinoma (RCC) had been investigated in previous studies; however, the results remain controversial. The primary aim of this meta-analysis was to investigate the prognostic and clinicopathological significance of the PD-L1 expression in patients with RCC. Relevant literature was identified form PubMed, Embase, Web of Science and Cochrane library, which compared the prognostic significance between PD-L1 expression and RCC. Hazard ratios (HRs) for survival outcomes and odds ratios (ORs) for clinical parameters associated with PD-L1 were extracted from eligible studies. Heterogeneity was assessed using the I² value. The fixed-effects model was used if there was no evidence of heterogeneity; otherwise, the random-effects model was used. Publication bias was evaluated using Begg’s funnel plots and Egger’s regression test. A total of 1863 patients from ten eligible studies were analyzed. The results showed that PD-L1 expression is associated with poor overall survival in clear cell RCC (ccRCC) (HR = 2.76, 95%CI: 2.25–3.38, I² = 14.4%, P < 0.001) and non-clear cell RCC (non-ccRCC) (HR = 2.77, 95%CI: 1.62–4.72, I² = 28.8%, P < 0.001). In addition, PD-L1 expression was found to be significantly associated with primary tumor stage (OR = 1.76, 95%CI: 1.39–2.23; I² = 56.3%), regional lymph node involvement (OR = 2.10, 95%CI: 1.48–2.98; I² = 14.9%), distant metastases (OR = 2.69, 95%CI: 2.05–3.54; I² = 0.0%), nuclear grade (OR = 1.72, 95%CI: 1.32–2.23; I² = 79.4%) and histologic tumor necrosis (OR = 2.25, 95%CI: 1.59–3.18; I² = 66.1%) in patients with RCC. The outcome stability was confirmed by sensitivity analysis. Both the Begg’s funnel plot test (P = 0.276) and the Egger’s (P = 0.388) verified that there was no publication bias within the included studies. This study suggests that PD-L1 expression is correlated with poor prognosis and advanced clinicopathological features in RCC patients.     

The tumor necrosis factor-α-238 polymorphism and digestive system cancer risk: a meta-analysis

Many studies have reported the association between tumor necrosis factor-α (TNF-α)-238 polymorphism and digestive system cancer susceptibility, but the results were inconclusive. We performed a meta-analysis to derive a more precise estimation of the relationship between TNF-α-238 G/A polymorphism and digestive system cancer risk. Pooled analysis for the TNF-α-238 G/A polymorphism contained 26 studies with a total of 4849 cases and 8567 controls. The meta-analysis observed a significant association between TNF-α-238 G/A polymorphism and digestive system cancer risk in the overall population (GA vs GG: OR 1.19, 95 % CI 1.00–1.40, P _{heterpgeneity} = 0.016; A vs G: OR 1.19, 95 % CI 1.03–1.39, P _{heterpgeneity} = 0.015; dominant model: OR 1.20, 95 % CI 1.02–1.41, P _{heterpgeneity} = 0.012). In the analysis of the ethnic subgroups, however, similar results were observed only in the Asian population, but not in the Caucasian population. Therefore, this meta-analysis suggests that TNF-α-238 G/A polymorphism is associated with a significantly increased risk of digestive system cancer. Further large and well-designed studies are needed to confirm these findings.     

Significance of decreased serum interleukin-10 levels in the progression of cerebral infarction

Anti-inflammatory cytokine and its serological detection may have an important role in the process of cardiovascular and cerebrovascular diseases. We investigated whether serum interleukin-10 (IL-10) is associated with cerebral infarction or not in the general population. Identified comprehensive searching was performed covering PubMed, EMBASE, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine, and China National Knowledge Infrastructure databases. Two reviewers extracted data and assessed studies independently. Information was extracted separately and classed into Asians and Caucasians. Summary standardized mean differences (SMDs) with 95 % confidence intervals (CI) were used with the utilization of Z test. Nine studies ranged from 2003 to 2014 were collected for meta-analysis. Results identified a negative association between serum IL-10 levels and cerebral infarction (SMD = 1.80, 95 % CI 0.79–2.81, P < 0.001). Country-subgroup analysis showed that low IL-10 level may be the main risk factor for cerebral infarction in India (SMD = 1.44, 95 % CI 1.13–1.75, P < 0.001) and Croatia (SMD = 2.96, 95 % CI 2.48–3.44, P < 0.001). In the ethnicity-stratified subgroup analysis, serum IL-10 levels were negatively correlated with cerebral infarction in Asians (SMD = 2.52, 95 % CI 0.47–4.57, P = 0.016), while not in Caucasians (P > 0.05). The lower serum IL-10 concentration was significantly associated with an increased likelihood of cerebral infarction in this meta-analysis. More prospective studies should be conducted to provide stronger evidence justifying the use of IL-10 as new biomarker to identify a predisposition toward cerebral infarction.     

Are EGFR tyrosine kinase inhibitors effective in elderly patients with EGFR-mutated non-small cell lung cancer?

EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib, gefitinib, and afatinib changed dramatically the history of metastatic non-small cell lung cancer (NSCLC) harbouring EGFR mutations. However, not enough data are available on the efficacy of these targeted drugs in elderly patients. The aim of this study is to analyse the available clinical data evaluating the efficacy of anti-EGFR therapies in elderly patients with advanced NSCLC carrying EGFR mutations. A literature-based meta-analysis of the results of randomized clinical trials was undertaken. Relevant publications from PubMed, the Cochrane Library, and abstracts from American Society of Clinical Oncology meetings were searched. Progression-free survival (PFS), as a measure of the efficacy of treatment, was the primary outcome investigated. The pooled analysis revealed an overall significant improvement in PFS (HR = 0.44, 95% CI 0.28–0.69; p = 0.0004) with the use of EGFR TKIs in EGFR-mutated NSCLC. The data stratification per age subgroups showed that EGFR TKIs were more effective in prolonging PFS in elderly patients, with HR 0.39 (p = 0.008), in comparison with young patients (HR = 0.48; p = 0.04). The results of this study suggest that EGFR TKIs have a significant effect in slowing down diseases progression in elderly patients with advanced NSCLC, therefore representing a valid therapeutic option in this age group.     

The relevance of Tim-3 polymorphisms and F protein to the outcomes of HCV infection

Hepatitis C virus (HCV) is one of the major causes of liver inflammation. The aim of this study was to investigate the associations of T-cell immunoglobulin and mucin domain-3 (Tim-3) polymorphisms and the alternate reading frame protein (F protein) with the outcomes of HCV infection. Three single-nucleotide polymorphisms (SNPs; rs10053538, rs12186731, and rs13170556) of Tim-3 were genotyped in this study, which included 203 healthy controls, 558 hepatitis C anti-F-positive patients, and 163 hepatitis C anti-F-negative patients. The results revealed that the rs12186731 CT and rs13170556 TC and CC genotypes were significantly less frequent in the anti-F-positive patients [odds ratio (OR)?=?0.54, 95 % confidence interval (CI)?=?0.35–0.83, p?=?0.005; OR?=?0.26, 95 % CI?=?0.18–0.39, p?<?0.001; and OR?=?0.19, 95 % CI?=?0.10–0.35, p?<?0.001, respectively), and the rs13170556 TC genotype was more frequent in the chronic HCV (CHC) patients (OR?=?1.70, 95 % CI?=?1.20–2.40, p?=?0.002). The combined analysis of the rs12186731 CT and rs13170556 TC/CC genotypes revealed a locus-dosage protective effect in the anti-F-positive patients (OR?=?0.22, 95 % CI?=?0.14–0.33, p _trend?<?0.001). Stratified analyses revealed that the frequencies of the rs12186731 (CT?+?TT) genotypes were significantly lower in the older (OR?=?0.31, 95 % CI?=?0.15–0.65, p?=?0.002) and female (OR?=?0.30, 95 % CI?=?0.17–0.52, p?<?0.001) subgroups, and rs13170556 (TC?+?CC) genotypes exhibited the same effect in all subgroups (all p?<?0.001) in the anti-F antibody generations. Moreover, the rs13170556 (TC?+?CC) genotypes were significantly more frequent in the younger (OR?=?1.86, 95 % CI?=?1.18–2.94, p?=?0.007) and female (OR?=?2.38, 95 % CI?=?1.48–3.83, p?<?0.001) subgroups of CHC patients. These findings suggest that the rs12186731 CT and rs13170556 TC/CC genotypes of Tim-3 provide potential protective effects with the F protein in the outcomes of HCV infection and that these effects are related to sex and age.     

Polymorphisms in DNA repair genes and breast cancer risk in Russian population: a case–control study

Genetic variation in DNA repair genes can alter an individual’s capacity to repair damaged DNA and influence the risk of cancer. We tested seven polymorphisms in DNA repair genes XRCC1, ERCC2, XRCC3, XRCC2, EXOI and TP53 for a possible association with breast cancer risk in a sample of 672 case and 672 control Russian women. An association was observed for allele A of the polymorphism XRCC1 (R399Q) rs25487 (co-dominant model AA vs. GG: OR 1.76, P = 0.003; additive model OR 1.28, P = 0.005; dominant model: OR 1.29, P = 0.03; recessive model OR 1.63, P = 0.008). Allele T of the polymorphism ERCC2 (D312N) rs1799793 was also associated with breast cancer risk (co-dominant model TT vs. CC: OR 1.43, P = 0.04; additive model OR 1.21, P = 0.02; dominant model: OR 1.30, P = 0.02), but the association became insignificant after applying Bonferroni correction. No association with breast cancer was found for the remaining SNPs. In summary, our study provides evidence that polymorphisms in DNA repair genes may play a role in susceptibility to breast cancer in the population of ethnical Russians.     

Genetic association between TAP1 and TAP2 polymorphisms and ankylosing spondylitis: a systematic review and meta-analysis

Objectives

Ankylosing spondylitis (AS) is a chronic inflammatory joint disease. The transporter associated with antigen processing (TAP) has been identified to play an important role in immune response as well as the HLA-associated diseases. The aim of our meta-analysis was to investigate the contribution of TAP (TAP1 and TAP2) polymorphisms to the risk of AS.

Methods

Meta-analyses were performed between 2 polymorphisms in TAP1 (TAP1-333, -637) and 3 polymorphisms in TAP2 (TAP2-379, -565, and -665) and AS.

Results

The meta-analyses were involved with 6 studies with 415 cases and 659 controls. Significant association was found between TAP1-333Val, TAP1-637Gly, and TAP2-565Thr and AS compared with combined control group (TAP1-333Val: p = 0.009, OR = 1.40, 95% CI 1.09–1.80; TAP1-637Gly: p = 0.002, OR = 1.48, 95% CI 1.15–1.91; p = 0.03, OR = 1.38, 95% CI 1.04–1.84). Subgroup analysis shown that significant association was only found in AS when compared with HLA-B27-negative controls (TAP1-333Val: p = 0.004, OR = 1.53, 95% CI 1.14–2.06; TAP1-637Gly: p = 0.004, OR = 1.52, 95% CI 1.15–2.02; p = 0.02, OR = 1.56, 95% CI 1.09–2.24), but not in AS when compared with HLA-B27-positive controls (p > 0.05). Moreover, no significant associations were found between haplotypes in TAP1 and TAP2 in both the combined and the subgroup analyses (p > 0.05).

Conclusions

TAP1-333Val, TAP1-637Gly, and TAP2-565Thr were likely to be associated with AS.

     

Differential role of Wnt signaling and base excision repair pathways in gastric adenocarcinoma aggressiveness

Aberrant activation of Wnt and base excision repair (BER) signaling pathways are implicated in tumor progression and chemotherapy resistance in gastric adenocarcinoma. This study was conducted to clarify the role of E2F6 and RhoA, components of the Wnt signaling pathway, and SMUG1, a component of the BER pathway in gastric adenocarcinoma. Expression levels and clinicopathological significance of three biomarkers, namely E2F6, RhoA, and SMUG1, as potential signaling molecules involved in tumorigenesis and aggressive behavior, were examined using tissue microarray. Our analysis showed a relative increase in the expression of E2F6 in gastric adenocarcinoma with no lymph node metastasis (χ ², P = 0.04 and OR, P = 0.08), while overexpression of RhoA and SMUG1 was found more often in the diffuse subtype of gastric adenocarcinoma as compared to the intestinal subtype (χ ², P = 0.05, OR, P = 0.08 and χ ², P = 0.001, OR, P = 0.009, respectively). Higher expression of RhoA was frequently seen in tumors with vascular invasion (χ ², P = 0.01 and OR, P = 0.01). In addition, increased expression of SMUG1 was found more often in poorly differentiated tumors (χ ², P = 0.01 and OR, P = 0.01). The distinct phenotype of E2F6^Low/SMUG1^High was more common in poorly differentiated tumors (P = 0.04) and with omental involvement (P = 0.01). The RhoA^High/SMUG1^High expression pattern was significantly more often found in diffuse subtype compared to the intestinal subtype (P = 0.001) as well as in poorly differentiated tumors (P = 0.004). The E2F6^Low/SMUG1^High and RhoA^High/SMUG1^High phenotypes can be considered as aggressive phenotypes of gastric adenocarcinoma. Our findings also demonstrated the synergistic effect of RhoA and SMUG1 in conferring tumor aggressiveness in diffuse subtype of gastric adenocarcinoma.     

Quantitative Volumetric K-Means Cluster Segmentation of Fibroglandular Tissue and Skin in Breast MRI

Mammographic breast density (MBD) is the most commonly used method to assess the volume of fibroglandular tissue (FGT). However, MRI could provide a clinically feasible and more accurate alternative. There were three aims in this study: (1) to evaluate a clinically feasible method to quantify FGT with MRI, (2) to assess the inter-rater agreement of MRI-based volumetric measurements and (3) to compare them to measurements acquired using digital mammography and 3D tomosynthesis. This retrospective study examined 72 women (mean age 52.4 ± 12.3 years) with 105 disease-free breasts undergoing diagnostic 3.0-T breast MRI and either digital mammography or tomosynthesis. Two observers analyzed MRI images for breast and FGT volumes and FGT-% from T1-weighted images (0.7-, 2.0-, and 4.0-mm-thick slices) using K-means clustering, data from histogram, and active contour algorithms. Reference values were obtained with Quantra software. Inter-rater agreement for MRI measurements made with 2-mm-thick slices was excellent: for FGT-%, r = 0.994 (95% CI 0.990–0.997); for breast volume, r = 0.985 (95% CI 0.934–0.994); and for FGT volume, r = 0.979 (95% CI 0.958–0.989). MRI-based FGT-% correlated strongly with MBD in mammography (r = 0.819–0.904, P < 0.001) and moderately to high with MBD in tomosynthesis (r = 0.630–0.738, P < 0.001). K-means clustering-based assessments of the proportion of the fibroglandular tissue in the breast at MRI are highly reproducible. In the future, quantitative assessment of FGT-% to complement visual estimation of FGT should be performed on a more regular basis as it provides a component which can be incorporated into the individual’s breast cancer risk stratification.     

Postoperative carcinoembryonic antigen level has a prognostic value for distant metastasis and survival in rectal cancer patients who receive preoperative chemoradiotherapy and curative surgery: a retrospective multi-institutional analysis

The cut-off value and prognostic significance of postoperative carcinoembryonic antigen (CEA) level in rectal cancer after preoperative chemoradiotherapy (CRT) and curative surgery are still unclear. 1559 rectal cancer patients staged with cT3-4N0-2M0 received preoperative CRT and total mesorectal excision (TME). CEA levels were measured before CRT and 3–4 weeks after surgery. Clinicopathologic factors that could be associated with tumor recurrence and patient survival were analyzed. The cumulative probability of tumor recurrence showed a steep increase with a cutoff value of 2.5 ng/mL for postoperative CEA level, and the gradient decreased as the CEA levels increased above 2.5 ng/mL. After a median follow-up time of 46.7 months, patients with postoperative CEA level >2.5 ng/mL had significantly lower relapse-free survival (RFS) (65.2 vs. 75.6 %, P < 0.001) and overall survival (OS) (78.1 vs. 88.3 %, P < 0.001) at 5 years than patients with postoperative CEA level ≤2.5 ng/mL. On the multivariate analysis, postoperative CEA level was a significant prognostic factor for RFS (HR 1.561; 95 % CI 1.221–1.996; P < 0.001) and OS (HR 2.073; 95 % CI 1.498–2.869; P < 0.001). Postoperative CEA level independently affected RFS irrespective of pre-CRT CEA level. Postoperative CEA level was a significant predictor for distant recurrence (P = 0.004), but not for locoregional recurrence (P = 0.472). Postoperative CEA level >2.5 ng/ml is a predictor of distant metastasis and a negative prognostic factor for survival in rectal cancer patients who receive preoperative CRT and curative surgery.     

Erratum to: Seasonal trend and clinical presentation of <Emphasis Type="Italic">Bacillus cereus</Emphasis> bloodstream infection: association with summer and indwelling catheter

Bacillus cereus, an opportunistic pathogen, can cause fatal infection. However, B. cereus bloodstream infections (BSIs) have not been well characterised. From 2008 to 2013, B. cereus isolates from all of the specimens and patients with B. cereus BSIs were identified. Environmental samples were collected to detect B. cereus contamination. We also characterised the clinical presentation of B. cereus BSI through analyses of risk factors for BSI and mortality. A total of 143 clinical B. cereus isolates was detected. Fifty-one patients with nosocomial infections were diagnosed as B. cereus BSI, and 37 had contaminated blood cultures. The number of B. cereus isolates and BSI patients was significantly greater from June to September than from January to April (3.4 vs. 1.0 per month and 1.4 vs. 0.2, respectively). All BSIs were nosocomial and related to central or peripheral vascular catheter. Urinary catheter [odds ratio (OR) 6.93, 95 % confidence interval (CI) 2.40–20.0] was the independent risk factor associated with BSI patients when compared to patients regarded as contaminated. In-hospital mortality among BSI patients was 20 % and was associated with urinary catheter (OR 12.3, 95 % CI 0.67–225, p=0.045) and higher Charlson index (OR 1.99, 95 % CI 1.26–3.12). The number of B. cereus isolates and BSI increased during summer. Inpatients with indwelling vascular or urinary catheters should be carefully monitored for potential B. cereus BSIs.     

Methylation status of <Emphasis Type="Italic">IGF2</Emphasis> DMR and <Emphasis Type="Italic">LINE1</Emphasis> in leukocyte DNA provides distinct clinicopathological features of gastric cancer patients

DNA methylation of leukocyte DNA has been proposed to be a biomarker for cancer that can be used to target patients for appropriate clinical implementation. We investigated IGF2 DMR and LINE1 methylation in the leukocyte DNA and their association with clinicopathological features and prognosis of gastric cancer (GC) patients. Methylation status of IGF2 DMR and LINE1 in the leukocyte DNA was quantified using bisulfite pyrosequencing in 207 GC patients. Methylation of both IGF2 DMR and the LINE1 was significantly higher in the undifferentiated histologic type compared to the differentiated histologic type (both P = 0.0002). Hypermethylation of both the IGF2 DMR and the LINE1 was associated with more aggressive features of GC such as advanced stage (IGF2 DMR, P = 0.0002; LINE1, P < 0.0001), lymphatic invasion positive (IGF2 DMR, P = 0.004; LINE1, P = 0.002), venous invasion positive (IGF2 DMR, LINE1, both P = 0.03), lymph node metastasis positive (IGF2 DMR, P = 0.01; LINE1, P = 0.001), peritoneal dissemination positive (IGF2 DMR, P = 0.04; LINE1, P = 0.002), liver metastasis positive (IGF2 DMR, P = 0.008; LINE1, P = 0.001), and other distant metastasis positive (IGF2 DMR, P = 0.04). Our data suggest that high LINE1 and IGF2 DMR methylation status would be a phenomenon that is observed with the progression of GC, supporting their potential utility as a biomarker in GC patients.     

Clinicopathological and prognostic significance of chemokine receptor CXCR4 in patients with bone and soft tissue sarcoma: a meta-analysis

The prognostic significance of CXC chemokine receptor 4 (CXCR4) in patients with bone and soft tissue sarcomas remains controversial. To investigate the impact of its expression on survival and clinicopathological features, we performed a meta-analysis. Comprehensive literature searches were conducted in PubMed, Web of Science, Embase and Cochrane Library for relevant studies. In total, 12 studies with 997 sarcoma patients were included. CXCR4 expression was found to be significantly associated with poor overall survival (HR 2.37, 95 % CI 1.86–3.01; P < 0.001). Further, when the analysis was stratified by histological subtypes (bony sarcoma including osteosarcoma and Ewing sarcoma and soft tissue sarcoma including synovial sarcoma and rhabdomyosarcoma), statistical analysis method (multivariate analysis and univariate analysis) and CXCR4 measuring method (IHC or RT-PCR), the significant correlation to poor overall survival was also observed except for that in Ewing sarcoma and RT-PCR groups. As for clinicopathological features, CXCR4 expression was significantly associated with higher rate of metastasis (OR 6.97, 95 % CI 2.28–21.31; P = 0.001) and higher tumor stage (OR 7.55, 95 % CI 1.25–45.47; P = 0.027), but not associated with gender, age and tumor site. In conclusion, CXCR4 expression may be an effective predictive factor of poor prognosis and clinicopathological features for bone and soft tissue sarcomas. Further studies are needed to validate our findings.