Expression and Prognostic Value of miR-486-5p in Patients with Gastric Adenocarcinoma

MicroRNA (miR)-486-5p expression is often reduced in human cancers. However, its expression in gastric carcinoma and its relation to clinicopathological features and prognosis are unclear. Tissue microarrays were constructed from 84 patients with gastric adenocarcinoma (GC) who were undergoing radical resection. miR-486-5p expression was detected by miRNA-locked nucleic acid in situ hybridization, and its correlations with clinicopathological features and overall survival were analyzed. Bioinformatic studies predict that fibroblast growth factor 9 (FGF9) is a potential target gene of miR-486-5p. miR-486-5p was mainly located in the cytoplasm of GC cells and neighboring normal tissues. Compared with paracancerous normal tissue, miR-486-5p expression was decreased in 63.1% (53/84) of the GC samples, increased in 32.1% (27/84) and unchanged in 4.8% (4/84). FGF9 expression was decreased in 69.0% (58/84) of GC samples and increased in 31.0% (26/84) compared with normal paracancerous tissues using immunohistochemical analysis. Low or unchanged miR-486-5p expression (P = 0.002), tumor stage (P = 0.001), tumor status (P = 0.001), node status (P = 0.001), tumor size (P = 0.004), and depth of tumor invasion (P = 0.013) were significant negative prognostic predictors for overall survival in patients with GC. After stratification according to American Joint Committee on Cancer (AJCC) stage, low/unchanged miR-486-5p expression remained a significant predictor of poor survival in stage II (P = 0.024) and stage III (P = 0.003). Cox regression analysis identified the following predictors of poor prognosis: tumor status (hazard ratio [HR], 7.19; 95% confidence interval [CI], 1.75–29.6; P = 0.006), stage (HR, 2.62; 95%CI, 1.50–4.59; P = 0.001), lymph node metastasis (HR, 2.52; 95% CI, 1.27–4.99; P = 0.008), low/unchanged miR-486-5p (HR, 2.47; 95% CI, 1.35–4.52; P = 0.003), high level of FGF9 (HR, 2.41; 95% CI, 1.42–4.09; P = 0.001) and tumor size (HR, 2.50; 95% CI, 1.30–4.82; P = 0.006). Low or unchanged expression of miR-486-5p compared with neighboring normal tissues was associated with a poor prognosis, while high expression was associated with a good prognosis in GC. miR-486-5p may thus be useful for evaluating prognosis and may provide a novel target treatment in patients with GC.     

PRR11 Is a Prognostic Marker and Potential Oncogene in Patients with Gastric Cancer

PRR11 is a potential candidate oncogene that has been implicated in the pathogenesis of lung cancer, however the role of PRR11 in gastric cancer is currently unclear. In the present study, we investigated the role of PRR11 in gastric cancer by evaluating its expression status in samples from a cohort of 216 patients with gastric cancer. PRR11 was found to be overexpressed in 107 (49.5%) patients by immunohistochemistry of tissue microarrays generated using the patient samples. Furthermore, PRR11 overexpression was found to correlate significantly with clinicopathologic features such as tumor invasion, tumor differentiation, and disease stage. Survival analysis of the cohort revealed that PRR11 is an independent prognostic factor for gastric cancer patients. PRR11 was stably silenced in a gastric carcinoma cell line using an shRNA-based approach, and treated cells showed decreased cellular proliferation and colony formation in vitro and cell growth in vivo, companied by decreased expression of CTHRC1 and increased expression of LXN, proteins involved in tumor progression. Evaluation of human gastric cancer samples demonstrated that PRR11 expression was also associated with increased CTHRC1 and decreased LXN expression. These data indicate that PRR11 may be widely activated in human gastric cancer and are consistent with the hypothesis that PRR11 functions as an oncogene in the development and progression of gastric cancer.     

High Diversity of vacA and cagA Helicobacter pylori Genotypes in Patients with and without Gastric Cancer

Background

Helicobacter pylori is associated with chronic gastritis, peptic ulcers, and gastric cancer. The aim of this study was to assess the topographical distribution of H. pylori in the stomach as well as the vacA and cagA genotypes in patients with and without gastric cancer.

Methodology/Principal Findings

Three gastric biopsies, from predetermined regions, were evaluated in 16 patients with gastric cancer and 14 patients with dyspeptic symptoms. From cancer patients, additional biopsy specimens were obtained from tumor centers and margins; among these samples, the presence of H. pylori vacA and cagA genotypes was evaluated. Positive H. pylori was 38% and 26% in biopsies obtained from the gastric cancer and non-cancer groups, respectively (p = 0.008), and 36% in tumor sites. In cancer patients, we found a preferential distribution of H. pylori in the fundus and corpus, whereas, in the non-cancer group, the distribution was uniform (p = 0.003). A majority of the biopsies were simultaneously cagA gene-positive and -negative. The fundus and corpus demonstrated a higher positivity rate for the cagA gene in the non-cancer group (p = 0.036). A mixture of cagA gene sizes was also significantly more frequent in this group (p = 0.003). Ninety-two percent of all the subjects showed more than one vacA gene genotype; s1b and m1 vacA genotypes were predominantly found in the gastric cancer group. The highest vacA-genotype signal-sequence diversity was found in the corpus and 5 cm from tumor margins.

Conclusion/Significance

High H. pylori colonization diversity, along with the cagA gene, was found predominantly in the fundus and corpus of patients with gastric cancer. The genotype diversity observed across systematic whole-organ and tumor sampling was remarkable. We find that there is insufficient evidence to support the association of one isolate with a specific disease, due to the multistrain nature of H. pylori infection shown in this work.     

淋巴结转移阴性的胃癌患者临床病理特征及生存探讨

目的:探讨淋巴结转移阴性胃癌患者的临床病理特征以及预后影响因素。方法:收集2000年1月至2009年1月我院收治的胃癌患者325例,其中经病理检查显示淋巴结转移阴性的105例患者作为阴性组(LN-组),另229例阳性患者作为阳性组(LN+组),比较两组的临床病理特征及临床预后。结果:LN-组的肿瘤直径、浸润深度及术后化疗与LN+组比较差异显著(P0.05);LN-组的5年生存率为76.2%,显著高于LN+组的43.2%(P0.05)。未透浆膜的LN-患者3年、5年生存率显著高于浸透浆膜者,术后化疗的LN-患者5年生存率显著高于未化疗者(P0.05),肿瘤直径5 cm的LN-患者3、5年生存率显著高于≥5 cm者(P0.05)。单因素分析显示浸润深度、肿瘤大小及术后化疗与LN-胃癌患者的预后具有密切关系(P0.05)。COX多因素分析显示浸润深度是影响LN-胃癌患者临床预后的独立因素(P0.05)。结论:淋巴结转移阴性胃癌患者的病灶多位于中下部,男性多于女性,发病年龄多在60岁以内,肿瘤直径多不超过5 cm,浸润深度多未浸透浆膜,临床预后优于淋巴结转移阳性胃癌患者,浸润深度是影响淋巴结转移阴性胃癌患者临床预后的独立因素。     

Stage-Stratified Analysis of Prognostic Significance of Tumor Size in Patients with Gastric Cancer

Background

The prognostic significance of tumor size in gastric cancer is not well defined. The objective of this study was to identify the prognostic value of tumor size in patients with gastric cancer.

Methods

We retrospectively reviewed a total of 1800 patients with gastric cancer admitted to our hospital between 1997 and 2007. These patients were divided into two groups according to tumor size: small size group (SSG, tumor ≤5 cm) and large size group (LSG, tumor >5 cm). We compared clinico-pathologic features of the two groups and investigated the prognostic factors by performing univariate, multivariate, and stage- stratified analyses according to tumor size.

Results

LSG had more aggressive clinico-pathologic features than SSG. Tumor size was an independent prognostic indicator in patients with gastric cancer. In a stratified-pT, pN, and pTNM analysis, survival of patients with LSG was significantly worse than that of patients with SSG and advanced stage. Tumor size was not a significant predictor of survival in patients with early stage tumors. Large tumor size was associated with shorter survival in patients with stages N0, N1, N2, and N3, and stages I, II, III, and IV.

Conclusions

Tumor size is a simple and practical prognostic factor in patients with gastric cancer. Tumor size could supplement clinical staging in the future.     

Prognostic Value of Survivin in Patients with Gastric Cancer: A Systematic Review with Meta-Analysis

Objective

The prognostic significance of survivin for the survival of patients with gastric cancer remains controversial. Thus, the objective of this study was to conduct a systematic review of the literature evaluating survivin expression in gastric cancer as a prognostic indicator.

Methods

Relevant literature was searched using PubMed, EMBASE, and Chinese biomedicine databases. A meta-analysis of the association between survivin expression and overall survival in patients with gastric cancer was performed. Studies were pooled and summary hazard ratios (HRs) were calculated. Subgroup analyses were also conducted.

Results

Final analysis of 1365 patients from 16 eligible studies was performed. Combined HR suggested that survivin expression had an unfavorable impact on survival of gastric cancer patients (HR=1.39, 95% CI: 1.16-1.68). The unfavorable impact also appeared significant when stratified according to the studies categorized by patients’ ethnicity, detection methods, type of sample, and HR estimate. The combined HR in the English literature showed an inverse effect on survival (HR=1.40, 95% CI: 1.13-1.75), while HR in the non-English literature did not (HR=1.38, 95% CI: 0.93-2.05). When stratified according to the location of survivin expression, combined HR showed that expression in cytoplasm was significantly associated with poor prognosis of gastric cancer patients (HR=1.46, 95% CI: 1.12-1.90). While expression in nucleus was not significantly associated with poor prognosis (HR=1.29, 95% CI: 0.72-2.31), the heterogeneity was highly significant (chi-squared=11.5, I²=74%, p=0.009).

Conclusions

This study showed that survivin expression was associated with a poor prognosis in patients with gastric cancer. Cytoplasmic expression of survivin may be regarded as a prognostic factor for gastric cancer patients. In contrast, survivin expression in nucleus did not have a significant impact on patients’ overall survival.     

Evaluation of Uric Acid as a Prognostic Blood-Based Marker in a Large Cohort of Pancreatic Cancer Patients

Background

Recently, chemical blood parameters gain more attraction as potential prognostic parameters in pancreatic cancer (PC). In the present study we investigated the prognostic relevance of the uric acid (UA) level in blood plasma at the time of diagnosis for overall survival (OS) in a large cohort of patients with PC.

Patients and Methods

Data from 466 consecutive patients with ductal adenocarcinoma of the pancreas were evaluated retrospectively. Overall survival (OS) was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of the UA level, univariate and multivariate Cox regression models were calculated.

Results

None of the clinicopathological parameters (tumour grade, clinical stage, age, CA19-9 level, Karnofski Index (KI) or surgical resection) except gender was associated with UA level. In univariate analysis we observed the elevated UA level (<5.1 versus ≥5.1 mg/dl, p = 0.017) as poor prognostic factor for OS. In the multivariate analysis that included age, gender, tumour grade, tumour stage, surgical resection, CA19-9 level, the KI and UA level we confirmed the UA level as independent prognostic factor for OS (HR = 1.373%; CI = 1.077–1.751; p = 0.011).

Conclusion

In conclusion, we identified the UA level at time of diagnosis as an independent prognostic factor in PC patients. Our results indicate that the UA level might represent a novel and useful marker for patient stratification in PC management.     

Expression and Prognostic Significance of Human Epidermal Growth Factor Receptors 1 and 3 in Gastric and Esophageal Adenocarcinoma

Background

Gastric and esophageal adenocarcinomas are major global cancer burdens. These cancer forms are characterized by a poor prognosis and a modest response to chemo- radio- and targeted treatment. Hence there is an obvious need for further enhanced diagnostic and treatment strategies. The aim of this study was to examine the expression and prognostic impact of human epidermal growth factor receptor 1 (HER1/EGFR) and 3 (HER3), as well as the occurrence of EGFR and KRAS mutations in gastric and esophageal adenocarcinoma.

Methods

Immunohistochemical expression of EGFR and HER3 was analysed in all primary tumours and a subset of lymph node metastases in a consecutive cohort of 174 patients with adenocarcinoma of the stomach, cardia and esophagus. The anti-HER3 antibody used was validated by siRNA-mediated knockdown, immunohistochemistry and quantitative real-time PCR. EGFR and KRAS mutation status was analysed by pyrosequencing tecchnology.

Results and Discussion

High EGFR expression was an independent risk factor for shorter overall survival (OS), whereas high HER3 expression was associated with a borderline significant trend towards a longer OS. KRAS mutations were present in only 4% of the tumours and had no prognostic impact. All tumours were EGFR wild-type. These findings contribute to the ongoing efforts to decide on the potential clinical value of different HERs and druggable mutations in gastric and esophageal adenocarcinomas, and attention is drawn to the need for more standardised investigational methods.     

Prognostic Significance of Neutrophil Lymphocyte Ratio in Patients with Gastric Cancer: A Meta-Analysis

Background

Several studies have shown that neutrophil lymphocyte ratio (NLR) may be associated with the prognosis of gastric cancer (GC), but the results are controversial.

Methods

This study was performed to evaluate the prognostic implications of neutrophil lymphocyte ratio of GC in all available studies. We surveyed 2 medical databases, PubMed and EMBASE, to identifyall relevant studies. Data were collected from studies comparing overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS) in patients with GC.

Results

Ten studies (n = 2,952) evaluated the role of NLR as a predictor of outcome were involved for this meta-analysis (10 for OS, 3 for DFS, and 2 for PFS). Overall and disease-free survival were significantly better in patients with low NLR value and the pooled HRs was significant at 1.83 ([95% CI], 1.62–2.07) and 1.58 ([95% CI], 1.12–2.21), respectively. For progression-free survival, the pooled hazard ratio of NLR was significant at 1.54 ([95% CI], 1.22–1.95). No evidence of significant heterogeneity or publication bias for OS and DFS was seen in any of the included studies.

Conclusion

This meta-analysis indicated that elevated NLR may be associated with a worse prognosis for patients with GC.     

Clinicopathological and Prognostic Significance of CD24 Overexpression in Patients with Gastric Cancer: A Meta-Analysis

Objective

The prognostic significance of CD24 expression for survival in patients with gastric cancer remains controversial. We conducted a meta-analysis to investigate the impact of CD24 expression on clinicopathological features and survival outcomes in gastric cancer.

Methods

A comprehensive literature search of the electronic databases PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI; up to April 8, 2014) was performed for relevant studies using multiple search strategies. Correlations between CD24 expression and clinicopathological features and overall survival (OS) were analyzed.

Results

A total of 1,041 patients with gastric cancer from 9 studies were included. The pooled odds ratios (ORs) indicated CD24 expression was associated with tumor depth (OR = 0.45, 95% confidence interval [CI]  = 0.32–0.63; P<0.00001), status of lymph nodes (OR = 0.40, 95% CI = 0.25–0.64; P = 0.0001) and tumor node metastasis (TNM) stage (OR = 0.56, 95% CI = 0.41–0.77; P = 0.0003). The pooled hazard ratio (HR) for OS showed overexpression of CD24 reduced OS in gastric cancer (HR = 1.99, 95% CI = 1.29–3.07, P = 0.002). Whereas, combined ORs showed that CD24 expression had no correlation with tumor differentiation or Lauren classifications.

Conclusion

CD24 overexpression in patients with gastric cancer indicated worse survival outcomes and was associated with common clinicopathological poor prognostic factors.     

Host Specificity and Source of Enterocytozoon bieneusi Genotypes in a Drinking Source Watershed

To assess the host specificity of Enterocytozoon bieneusi and to track the sources of E. bieneusi contamination, we genotyped E. bieneusi in wildlife and stormwater from the watershed of New York City''s source water, using ribosomal internal transcribed spacer (ITS)-based PCR and sequence analyses. A total of 255 specimens from 23 species of wild mammals and 67 samples from stormwater were analyzed. Seventy-four (29.0%) of the wildlife specimens and 39 (58.2%) of the stormwater samples from streams were PCR positive. Altogether, 20 E. bieneusi genotypes were found, including 8 known genotypes and 12 new ones. Sixteen and five of the genotypes were seen in animals and stormwater from the watershed, respectively, with WL4 being the most common genotype in both animals (35 samples) and stormwater (23 samples). The 20 E. bieneusi genotypes belonged to five genogroups (groups 1, 3, 4, and 7 and an outlier), with only 23/113 (20.4%) E. bieneusi-positive samples belonging to zoonotic genogroup 1 and 3/20 genotypes ever being detected in humans. The two genogroups previously considered host specific, groups 3 and 4, were both detected in multiple groups of mammals. Thus, with the exception of the type IV, Peru11, and D genotypes, which were detected in only 7, 5, and 2 animals, respectively, most E. bieneusi strains in most wildlife samples and all stormwater samples in the watershed had no known public health significance, as these types have not previously been detected in humans. The role of different species of wild mammals in the contribution of E. bieneusi contamination in stormwater was supported by determinations of host-adapted Cryptosporidium species/genotypes in the same water samples. Data from this study indicate that the host specificity of E. bieneusi group 3 is broader than originally thought, and wildlife is the main source of E. bieneusi in stormwater in the watershed.     

Prognostic Significance of Systemic Inflammation-Based Lymphocyte- Monocyte Ratio in Patients with Lung Cancer: Based on a Large Cohort Study

Increasing evidence indicates cancer-related inflammatory biomarkers show great promise for predicting the outcome of cancer patients. The lymphocyte- monocyte ratio (LMR) was demonstrated to be independent prognostic factor mainly in hematologic tumor. The aim of the present study was to investigate the prognostic value of LMR in operable lung cancer. We retrospectively enrolled a large cohort of patients with primary lung cancer who underwent complete resection at our institution from 2006 to 2011. Inflammatory biomarkers including lymphocyte count and monocyte count were collected from routinely performed preoperative blood tests and the LMR was calculated. Survival analyses were calculated for overall survival (OS) and disease-free survival (DFS). A total of 1453 patients were enrolled in the study. The LMR was significantly associated with OS and DFS in multivariate analyses of the whole cohort (HR = 1.522, 95% CI: 1.275–1.816 for OS, and HR = 1.338, 95% CI: 1.152–1.556 for DFS). Univariate subgroup analyses disclosed that the prognostic value was limited to patients with non-small-cell lung cancer (NSCLC) (HR: 1.824, 95% CI: 1.520–2.190), in contrast to patients with small cell lung cancer (HR: 1.718, 95% CI: 0.946–3.122). Multivariate analyses demonstrated that LMR was still an independent prognostic factor in NSCLC. LMR can be considered as a useful independent prognostic marker in patients with NSCLC after complete resection. This will provide a reliable and convenient biomarker to stratify high risk of death in patients with operable NSCLC.     

Preoperative Plasma Fibrinogen Level Represents an Independent Prognostic Factor in a Chinese Cohort of Patients with Upper Tract Urothelial Carcinoma

Background

Increased plasma fibrinogen is thought to contribute to tumor progression and metastasis. The association of plasma fibrinogen with clinicopathological characteristics, and the optimal cutoff with an ideal predictive value has not been fully determined in patients with upper tract urothelial carcinoma (UTUC). We aimed to investigate the clinical significance of this parameter in a Chinese cohort of patients with UTUC.

Methods

A retrospective study was conducted to analyze the clinical data of 184 operable UTUC patients in a Chinese cohort with a high incidence of chronic kidney disease (CKD). An optimal cutoff was set for further analysis according to validated web-based software. The associations of plasma fibrinogen with clinicopathological characteristics and survival were assessed. Multivariate analyses were performed to determine the independent prognostic factors.

Results

Elevated plasma fibrinogen was significantly associated with tumor necrosis, lymph node involvement, and a higher preoperative CKD stage, pathological tumor stage and grade (all P < 0.05). Kaplan-Meier analysis showed that plasma fibrinogen ≥ 3.54 g/L predicted a poorer overall and cancer-specific survival than < 3.54 g/L (P < 0.001 for both). Multivariate analyses revealed that elevated preoperative plasma fibrinogen was an independent negative prognostic factor for overall survival (HR = 2.026; 95% CI: 1.226–3.349; P = 0.006) and cancer-specific survival (HR = 1.886; 95% CI: 1.019–3.490; P = 0.043).

Conclusions

Increased plasma fibrinogen was an independent prognostic risk factor for poor outcomes in UTUC. This parameter may serve as an effective biomarker with easy accessibility for evaluating prognosis for patients with UTUC.     

Prognostic Role of Functional Neuroimaging after Multilobar Resection in Patients with Localization-Related Epilepsy

To investigate the usage of functional neuroimaging as a prognostic tool for seizure recurrence and long-term outcomes in patients with multilobar resection, we recruited 90 patients who received multilobar resections between 1995 and 2013 with at least 1-year follow-up (mean 8.0 years). All patients were monitored using intracranial electroencephalography (EEG) after pre-surgical evaluation. Clinical data (demographics, electrophysiology, and neuroimaging) were reviewed retrospectively. Surgical outcomes were evaluated at 1, 2, 5 years after surgery, and at the end of the study. After 1 year, 56 patients (62.2%) became Engel class I and at the last follow-up, 47 patients (52.2%) remained seizure-free. Furthermore, non-localized ¹⁸F-fluorodeoxyglucose positron emission tomography (PET), identifying hypometabolic areas not concordant with ictal onset zones, significantly correlated with seizure recurrence after 1 year. Non-lesional magnetic resonance imaging (MRI) and left-sided resection correlated with poor outcomes. In the last follow-up, non-localized PET and left-sided resection significantly correlated with seizure recurrence. Both localized PET and ictal-interictal SPECT subtraction co-registered to MR (SISCOM) predicted good surgical outcomes in the last follow-up (69.2%, Engel I). This study suggests that PET and SISCOM may predict postoperative outcomes for patients after multilobar epilepsy and shows comparable long-term surgical outcomes after multilobar resection.     

Reduced Expression of Uroplakin 1A Is Associated with the Poor Prognosis of Gastric Adenocarcinoma Patients

Background

The aim of this study was to investigate the expression and prognostic significance of Uroplakin1A (UPK1A) in gastric adenocarcinoma patients. Functional studies were also analyzed in vitro.

Methodology/Principal Findings

Real-time quantitative PCR (RT-qPCR), western blotting, and immunohistochemical (IHC) staining methods were used to analyze the expression of UPK1A in primary gastric adenocarcinoma tissue samples. Compared with matched adjacent non-tumor, the expression of UPK1A in fresh surgical specimens was reduced, which was confirmed by RT-qPCR (P<0.01) and western blotting analysis (P<0.01). The paraffin specimens from a consecutive series of 445 gastric adenocarcinoma patients who underwent surgery between 2003 and 2006 were analyzed by IHC staining. The relationship between UPK1A expression, clinicopathological factors, and survival were evaluated. IHC staining analysis revealed that the reduced expression of UPK1A was observed in 224 cases (50.3%). Additionally, the correlation analysis of clinicopathological factors demonstrated that reduced expression of UPK1A was significantly associated with histological grade (P = 0.022), node metastasis (P<0.001) and tumor node metastasis (TNM) stage (P = 0.008) (7^th edition of the International Union Against Cancer (UICC)). Furthermore, Kaplan-Meier survival analysis revealed that the reduced expression of UPK1A was significantly associated with poor prognosis (P = 0.043). Cox hazards model analysis indicated that UPK1A expression was an independent risk factor at the 0.1 level (P = 0.094). The function of UPK1A in cell cycle, migration, and invasion was investigated by overexpressing UPK1A in the MKN45 gastric cancer cell line. The elevated expression of UPK1A cells induced G1 phase arrest and significantly inhibited migration and invasion.

Conclusions/Significance

The reduced expression of UPK1A might play a role in the progression of gastric cancer. Thus, UPK1A could be a potential favorable biomarker associated with gastric cancer prognosis.     

Prognostic Value of the Six-Second Spirometry in Patients with Chronic Obstructive Pulmonary Disease: A Cohort Study

BackgroundThe six-second spirometry has been proposed as an alternative to diagnose airflow limitation, although its prognostic value in patients with chronic obstructive pulmonary disease (COPD) remains unknown. The purpose of this study was to determine the prognostic value of the postbronchodilator forced expiratory volume in 1 second (FEV₁)/forced expiratory volume in 6 seconds (FEV₆) ratio and FEV₆ in COPD patients.ConclusionsIn a general COPD outpatient population, airflow obstruction assessed by the FEV₁/FEV₆ is an independent risk factor for both death and hospitalization.     

Podocalyxin as a Prognostic Marker in Gastric Cancer

Background

Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein associated with aggressive tumor phenotype and poor prognosis in several forms of cancer. The aim of this study was to investigate PODXL expression in gastric cancer by use of two different antibodies.

Methods

By tumor-tissue microarrays and immunohistochemistry we evaluated PODXL expression in tumor specimens from 337 patients who underwent surgery for gastric adenocarcinoma at Helsinki University Hospital. We used two different antibodies: HPA2110, which is a polyclonal antibody and an in-house monoclonal antibody called HES9, to investigate the association of PODXL expression with clinicopathologic variables and patient survival.

Results

PODXL staining was positive by the polyclonal antibody in 153 (57.5%) cases and by the monoclonal antibody in 212 (76%). Polyclonal antibody expression was associated with intestinal cancer type (p<0.001). Monoclonal antibody staining was associated with age over 66 (p = 0.001), with intestinal cancer (p<0.001), and with small tumor size (≤ 5 cm; p = 0.024). Both antibodies were associated with high S-phase fraction (p = 0.022; p = 0.010), and high tumor proliferation index (Ki-67; p = 0.003; p = 0.001). PODXL positivity by the polyclonal antibody indicated reduced gastric-cancer-specific 5-year survival of 24.0% (95% CI 16.9–31.1), compared to 43.3% (95% CI 33.7–52.9) for patients with PODXL negativity (p = 0.001). The result remained significant in multivariable analysis (HR = 3.17; 95% CI 1.37–7.34, p = 0.007).

Conclusion

In gastric cancer, PODXL expression by the polyclonal antibody HPA2110 is an independent marker of poor prognosis.     

Investigating the Association of ApoE Genotypes with Blood-Brain Barrier Dysfunction Measured by Cerebrospinal Fluid-Serum Albumin Ratio in a Cohort of Patients with Different Types of Dementia

Background

Since more than a decade ApoE is known to be a strong risk factor for Alzheimer''s disease (AD); however, molecular pathways mediating this risk are still unclear. In recent years it has been hypothesized that ApoE might play a role in the disintegration of blood-brain barrier (BBB). In the present study we addressed the question if ApoE genotypes might be associated with BBB function measured by albumin ratio (Q_Alb) in a large cohort of patients with different types of dementia.

Methods

Five hundred twenty (520) patients with Creutzfeldt-Jakob disease (CJD, n = 350), Alzheimer''s disease (n = 71) and cerebral small vessel disease (n = 99) were assessed for their ApoE genotype. BBB function was measured in all patients using Q_Alb and was compared between ApoE genotypes. Dominant and additive genetic models were assumed in order to investigate the potential effect of ApoE on BBB function.

Results

We observed no systematic differences in Q_Alb between ApoE genotypes within the present study. Increased Q_Alb levels were shown for those without E3 allele in the subgroup of CJD patients when assuming a dominant genetic model (p = 0.035). This could not be confirmed for patients with other forms of dementia (p = 0.234).

Discussion

Although there was some evidence for a protective effect of E3 alleles in CJD patients, this study does not support the hypothesis of a systematic role of ApoE genotypes in BBB function in individuals with a diagnosis of dementia. Thus, changes in BBB function do not seem to contribute to the increased risk of cognitive decline associated with certain ApoE genotypes. The interpretation of the results of this study must take into account that BBB function was only assessed by measuring Q_Alb which has been shown to be a good marker for overall BBB integrity but might not reflect all qualities of the barrier.