Clinical meaning of age-related expression of fecal cytokeratin 19 in colorectal malignancy

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) is one of the leading causes of malignant death worldwide. Because young age of onset is often considered a poor prognostic factor for CRC, it is important to identify the poor outcomes of CRC in a younger population and to consider an aggressive approach by implementing early treatment. Our aim was to specifically quantify the fecal cytokeratin 19 (CK19) transcript from CRC patients and investigate its correlation with clinical stage, tumor malignancy, and age.</p> <p>Methods</p> <p>The quantitation of fecal CK19 transcript was determined by a quantitative real-time reverse transcription polymerase chain in 129 CRC patients (45 younger than 60 years at diagnosis) and 85 healthy controls. The levels of CK19 protein were examined both in colonic cell lines and tissues.</p> <p>Results</p> <p>The analysis of 45 younger CRC patients (age ≤ 60 years) revealed that patients at the M1 stage had significantly higher expression levels of fecal CK19 mRNA when compared with healthy controls (<it>p </it>< 0.001) and patients at the M0 stage (<it>p </it>= 0.004). Additionally, the degree of consistency between the mean level of fecal CK19 mRNA and the distant metastatic rate in each age interval was up to 89% (<it>p </it>= 0.042).</p> <p>Conclusion</p> <p>These results indicate that high levels of fecal CK19 mRNA represent a potential marker for colorectal malignancy and for aggressive treatment of younger CRC patients.</p

Subclinical Histologic Chorioamnionitis and Related Clinical and Laboratory Parameters in Preterm Deliveries

Histologic chorioamnionitis (HCA) is associated with preterm delivery and with neonatal morbidity and mortality. Because HCA is usually subclinical, histologic examination of the placenta is essential for confirmatory diagnosis. In the present study, the correlations between subclinical HCA and relevant clinical and laboratory parameters were analyzed. Methods: This was a retrospective study. We reviewed the placental histopathologic findings and the charts of patients who were admitted to our neonatal intensive care unit after delivery and their mothers between January 2007 and March 2008. A total of 77 preterm infants [gastational age (GA): 32.2 ± 3.4 weeks, birth weight (BW): 1,718 ± 554 g] were categorized as group A with histologic evidence of placental inflammation (n = 27) or group B without histologic evidence of placental inflammation (n = 50). Placental histology was studied to identify the presence of inflammatory states such as chorioamnionitis, funisitis and deciduitis. Laboratory parameters including complete blood count, differential count, and C-reactive protein (CRP) level of mothers and initial arterial blood gas, glucose level and mean blood pressure of the infants were documented. Gestational age, Apgar score, history of prolonged premature rupture of membrane (prolonged PROM), gestational diabetes mellitus, meconium-stained amniotic fluid, pregnancy-induced hypertension and signs of pre-eclampsia were also collected as clinical parameters. All data were analyzed using independent t tests and Fisher's exact test, as appropriate. Results: Group A newborns had a significantly lower gestational age (30.8 ± 4.1 weeks vs. 33.0 ± 2.6 weeks, p < 0.05) and higher CRP level (0.56 ± 0.92 mg/dL vs. 0.12 ± 0.14 mg/dL, p < 0.05), together with higher maternal WBC count (13,002 ± 4,344/μL vs. 10,850 ± 3,722/μL, p < 0.05) and higher rate of prolonged PROM [14/27 (51.85%) vs. 8/37 (21.62%), p < 0.05] compared with group B newborns. Conclusion: We found that HCA was significantly correlated with lower gestational age, higher CRP level of preterm infants, higher maternal WBC count, and a higher rate of prolonged PROM. Our results demonstrate a significant association between HCA with an elevated CRP level in preterm infants. These findings further confirmed the association between maternal inflammation and preterm deliveries

Promoter Methylation status of HIN-1 associated with outcomes of ovarian clear cell adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>This study is to analyze promoter methylation of various tumor suppressor genes in different types of ovarian carcinoma and to identify potential therapeutic targets of ovarian clear cell adenocarcinoma (OCCA).</p> <p>Materials and methods</p> <p>The promoter methylation statuses of 40 genes in primary ovarian carcinomas including 47 clear- and 63 non-clear-cell type tissues, 6 OCCA cell lines, 29 benign ovarian endometriotic cysts, and 31 normal controls were analyzed by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). The MS-MLPA results were correlated with clinicopathological features and outcomes of 47 OCCA patients. Functions of the target genes were further explored by Western Blot Analysis, apoptosis assay, and caspase-3/7 activity analysis.</p> <p>Results</p> <p>Frequencies of methylated RASSF1A, CDH13, CACNA1A, HIN-1, and sFRP5 genes in OCCA tissues were significantly higher than those in non-OCCA cancerous tissues and benign endometriotic cysts<b>.</b> The expected OS for patients with methylated promoters of HIN-1 was significantly worse than those for patients without methylated HIN-1 (30% vs. 62%, <it>p</it> = 0.002). The HIN-1 gene was over-expressed in ES2 cells, a significant reduction in cell growth and induction of apoptosis, and increasing paclitaxel sensitivity by reducing phosphorylation of Akt were observed.</p> <p>Conclusions</p> <p>Methylation of HIN-1 promoter is a novel epigenetic biomarker associated with poor outcomes in OCCA patients. Ectopic expression of the HIN-1 gene increased paclitaxel sensitivity which is partly through Akt pathway.</p

Prediction consistency and clinical presentations of breast cancer molecular subtypes for Han Chinese population

<p>Abstract</p> <p>Background</p> <p>Breast cancer is a heterogeneous disease in terms of transcriptional aberrations; moreover, microarray gene expression profiles had defined 5 molecular subtypes based on certain intrinsic genes. This study aimed to evaluate the prediction consistency of breast cancer molecular subtypes from 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50) as well as clinical presentations of each molecualr subtype in Han Chinese population.</p> <p>Methods</p> <p>In all, 169 breast cancer samples (44 from Taiwan and 125 from China) of Han Chinese population were gathered, and the gene expression features corresponding to 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50) were retrieved for molecular subtype prediction.</p> <p>Results</p> <p>For Sørlie 500 and Hu 306 intrinsic gene set, mean-centring of genes and distance-weighted discrimination (DWD) remarkably reduced the number of unclassified cases. Regarding pairwise agreement, the highest predictive consistency was found between Hu 306 and PAM50. In all, 150 and 126 samples were assigned into identical subtypes by both Hu 306 and PAM50 genes, under mean-centring and DWD. Luminal B tended to show a higher nuclear grade and have more HER2 over-expression status than luminal A did. No basal-like breast tumours were ER positive, and most HER2-enriched breast tumours showed HER2 over-expression, whereas, only two-thirds of ER negativity/HER2 over-expression tumros were predicted as HER2-enriched molecular subtype. For 44 Taiwanese breast cancers with survival data, a better prognosis of luminal A than luminal B subtype in ER-postive breast cancers and a better prognosis of basal-like than HER2-enriched subtype in ER-negative breast cancers was observed.</p> <p>Conclusions</p> <p>We suggest that the intrinsic signature Hu 306 or PAM50 be used for breast cancers in the Han Chinese population during molecular subtyping. For the prognostic value and decision making based on intrinsic subtypes, further prospective study with longer survival data is needed.</p