Heterogeneous nuclear ribonucleoprotein K is over expressed, aberrantly localised and is associated with poor prognosis in colorectal cancer

Heterogeneous ribonucleoprotein K (hnRNP K) is a member of the hnRNP family which has several different cellular roles including transcription, mRNA shuttling, RNA editing and translation. Several reports implicate hnRNP K having a role in tumorigenesis, for instance hnRNP K increases transcription of the oncogene c-myc and hnRNP K expression is regulated by the p53/MDM 2 pathway. In this study comparing normal colon to colorectal cancer by proteomics, hnRNP K was identified as being overexpressed in this type of cancer. Immunohistochemistry with a monoclonal antibody to hnRNP K (which we developed) on colorectal cancer tissue microarray, confirmed that hnRNP K was overexpressed in colorectal cancer (P<0.001) and also showed that hnRNP K had an aberrant subcellular localisation in cancer cells. In normal colon hnRNP K was exclusively nuclear whereas in colorectal cancer the protein localised both in the cytoplasm and the nucleus. There were significant increases in both nuclear (P=0.007) and cytoplasmic (P=0.001) expression of hnRNP K in Dukes C tumours compared with early stage tumours. In Dukes C patient's good survival was associated with increased hnRNP K nuclear expression (P=0.0093). To elaborate on the recent observation that hnRNP K is regulated by p53, the expression profiles of these two proteins were also analysed. There was no correlation between hnRNP K and p53 expression, however, patients who presented tumours that were positive for hnRNP K and p53 had a poorer survival outcome (P=0.045)

Expression profile of microRNAs in young stroke patients

10.1371/journal.pone.0007689PLoS ONE41

Differential Expression Profile and Genetic Variants of MicroRNAs Sequences in Breast Cancer Patients

The technology available for cancer diagnosis and prognosis is not yet satisfactory at the molecular level, and requires further improvements. Micro RNAs (miRNAs) have been recently reported as useful biomarkers in diseases including cancer. We performed a miRNA expression profiling study using peripheral blood from breast cancer patients to detect and identify characteristic patterns. A total of 100 breast cancer patients and 89 healthy patients were recruited for miRNA genotyping and expression profiling. We found that hs-miR-196a2 in premenopausal patients, and hs-miR-499, hs-miR-146a and hs-miR-196a2 in postmenopausal patients, may discriminate breast cancer patients from healthy individuals. In addition, we found a significant association between two microRNA polymorphisms (hs-miR-196a2 and hs-miR-499) and breast cancer risk. However, no significant association between the hs-miR-146a gene and breast cancer risk was found. In summary, the study demonstrates that peripheral blood miRNAs and their expression and genotypic profiles can be developed as biomarkers for early diagnosis and prognosis of breast cancer

The fatty acid binding protein 7 (FABP7) is involved in proliferation and invasion of melanoma cells

<p>Abstract</p> <p>Background</p> <p>The molecular mechanisms underlying melanoma tumor development and progression are still not completely understood. One of the new candidates that emerged from a recent gene expression profiling study is <it>fatty acid-binding protein 7 </it>(<it>FABP7)</it>, involved in lipid metabolism, gene regulation, cell growth and differentiation.</p> <p>Methods</p> <p>We studied the functional role of FABP7 in human melanoma cell lines and using immunohistochemistry analyzed its expression pattern and clinical role in 11 nevi, 149 primary melanomas and 68 metastases.</p> <p>Results</p> <p>FABP7 mRNA and protein level is down-regulated following treatment of melanoma cell lines with a PKC activator (PMA) or MEK1 inhibitor (PD98059). Down-regulation of FABP7 using siRNA decreased cell proliferation and invasion but did not affect apoptosis. In clinical specimens, FABP7 was expressed in 91% of nevi, 71% of primary melanomas and 70% of metastases, with a cytoplasmic and/or nuclear localization. FABP7 expression was associated with tumor thickness in superficial spreading melanoma (P = 0.021). In addition, we observed a trend for an association between FABP7 expression and Ki-67 score (P = 0.070) and shorter relapse-free survival (P = 0.069) in this group of patients.</p> <p>Conclusion</p> <p>Our data suggest that FABP7 can be regulated by PKC and the MAPK/ERK1/2 pathway through independent mechanisms in melanoma cell lines. Furthermore, FABP7 is involved in cell proliferation and invasion <it>in vitro</it>, and may be associated with tumor progression in melanoma.</p

Proteome analysis of human gastric cardia adenocarcinoma by laser capture microdissection

<p>Abstract</p> <p>Background</p> <p>The incidence of gastric cardiac adenocarcinoma (GCA) has been increasing in the past two decades in China, but the molecular changes relating to carcinogenesis have not been well characterised.</p> <p>Methods</p> <p>In this study, we used a comparative proteomic approach to analyse the malignant and nonmalignant gastric cardia epithelial cells isolated by navigated laser capture microdissection (LCM) from paired surgical specimens of human GCA.</p> <p>Results</p> <p>Twenty-seven spots corresponding to 23 proteins were consistently differentially regulated. Fifteen proteins were shown to be up-regulated, while eight proteins were shown to be down-regulated in malignant cells compared with nonmalignant columnar epithelial cells. The identified proteins appeared to be involved in metabolism, chaperone, antioxidation, signal transduction, apoptosis, cell proliferation, and differentiation. In addition, expressions of HSP27, 60, and Prx-2 in GCA specimens were further confirmed by immunohistochemical and western blot analyses.</p> <p>Conclusion</p> <p>These data indicate that the combination of navigated LCM with 2-DE provides an effective strategy for discovering proteins that are differentially expressed in GCA. Such proteins may contribute in elucidating the molecular mechanisms of GCA carcinogenesis. Furthermore, the combination provides potential clinical biomarkers that aid in early detection and provide potential therapeutic targets.</p

Computational prediction and experimental validation associating FABP-1 and pancreatic adenocarcinoma with diabetes

<p/> <p>Background</p> <p>Pancreatic cancer, composed principally of pancreatic adenocarcinoma (PaC), is the fourth leading cause of cancer death in the United States. PaC-associated diabetes may be a marker of early disease. We sought to identify molecules associated with PaC and PaC with diabetes (PaC-DM) using a novel translational bioinformatics approach. We identified fatty acid binding protein-1 (FABP-1) as one of several candidates. The primary aim of this pilot study was to experimentally validate the predicted association between FABP-1 with PaC and PaC with diabetes.</p> <p>Methods</p> <p>We searched public microarray measurements for genes that were specifically highly expressed in PaC. We then filtered for proteins with known involvement in diabetes. Validation of FABP-1 was performed via antibody immunohistochemistry on formalin-fixed paraffin embedded pancreatic tissue microarrays (FFPE TMA). FFPE TMA were constructed using148 cores of pancreatic tissue from 134 patients collected between 1995 and 2002 from patients who underwent pancreatic surgery. Primary analysis was performed on 21 normal and 60 pancreatic adenocarcinoma samples, stratified for diabetes. Clinical data on samples was obtained via retrospective chart review. Serial sections were cut per standard protocol. Antibody staining was graded by an experienced pathologist on a scale of 0-3. Bivariate and multivariate analyses were conducted to assess FABP-1 staining and clinical characteristics.</p> <p>Results</p> <p>Normal samples were significantly more likely to come from younger patients. PaC samples were significantly more likely to stain for FABP-1, when FABP-1 staining was considered a binary variable. Compared to normals, there was significantly increased staining in diabetic PaC samples (p = 0.004) and there was a trend towards increased staining in the non-diabetic PaC group (p = 0.07). In logistic regression modeling, FABP-1 staining was significantly associated with diagnosis of PaC (OR 8.6 95% CI 1.1-68, p = 0.04), though age was a confounder.</p> <p>Conclusions</p> <p>Compared to normal controls, there was a significant positive association between FABP-1 staining and PaC on FFPE-TMA, strengthened by the presence of diabetes. Further studies with closely phenotyped patient samples are required to understand the true relationship between FABP-1, PaC and PaC-associated diabetes. A translational bioinformatics approach has potential to identify novel disease associations and potential biomarkers in gastroenterology.</p