Independent prognostic genes and mechanism investigation for colon cancer

PROPOSE: We aimed to explore the potential molecular mechanism and independent prognostic genes for colon cancer (CC). METHODS: Microarray datasets GSE17536 and GSE39582 were downloaded from Gene Expression Omnibus. Meanwhile, the whole CC-related dataset were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNA (DEMs) were identified between cancer tissue samples and para-carcinoma tissue samples in TCGA dataset, followed by the KEGG pathway and GO function analyses. Furthermore, the clinical prognostic analysis including overall survival (OS) and disease-free survival (DFS) were performed in all three datasets. RESULTS: A total of 633 up- and 321 down-regulated mRNAs were revealed in TCGA dataset. The up-regulated mRNAs were mainly assembled in functions including extracellular matrix and pathways including Wnt signaling. The down-regulated mRNAs were mainly assembled in functions like Digestion and pathways like Drug metabolism. Furthermore, up-regulation of UL16-binding protein 2 (ULBP2) was associated with OS in CC patients. A total of 12 DEMs including Surfactant Associated 2 (SFTA2) were potential DFS prognostic genes in CC patients. Meanwhile, the GRP and Transmembrane Protein 37 (TMEM37) were two outstanding independent DFS prognostic genes in CC. CONCLUSIONS: ULBP2 might be a potential novel OS prognostic biomarker in CC, while GRP and TMEM37 could be served as the independent DFS prognostic genes in CC. Furthermore, functions including extracellular matrix and digestion, as well as pathways including Wnt signaling and drug metabolism might play important roles in the process of CC.

Decreased Expression of Surfactant Protein Genes Is Associated with an Increased Expression of Forkhead Box M1 Gene in the Fetal Lung Tissues of Premature Rabbits

PURPOSE: Recently, Forkhead box M1 (FoxM1) was reported to be correlated with lung maturation and expression of surfactant proteins (SPs) in mice models. However, no study has been conducted in rabbit lungs despite their high homology with human lungs. Thus, we attempted to investigate serial changes in the expressions of FoxM1 and SP-A/B throughout lung maturation in rabbit fetuses. MATERIALS AND METHODS: Pregnant New Zealand White rabbits were grouped according to gestational age from 5 days before to 2 days after the day of expected full term delivery (F5, F4, F3, F2, F1, F0, P1, and P2). A total of 64 fetuses were enrolled after Cesarean sections. The expressions of mRNA and proteins of FoxM1 and SP-A/B in fetal lung tissue were tested by quantitative reverse-transcriptase real-time PCR and Western blot. Furthermore, their correlations were analyzed. RESULTS: The mRNA expression of SP-A/B showed an increasing tendency positively correlated with gestational age, while the expression of FoxM1 mRNA and protein decreased from F5 to F0. A significant negative correlation was found between the expression levels of FoxM1 and SP-A/B (SP-A: R=-0.517, p=0.001; SP-B: R=-0.615, p<0.001). CONCLUSION: Preterm rabbits demonstrated high expression of FoxM1 mRNA and protein in the lungs compared to full term rabbits. Also, the expression of SP-A/B was inversely related with serial changes in FoxM1 expression. This is the first report to suggest an association between FoxM1 and expression of SP-A/B and lung maturation in preterm rabbits.

Efectos de la malnutricion proteico-calorica materna sobre la concentracion del ARN mensajero de la proteina A del surfactante en pulmones de ratas fetales / Effects of maternal protein-calorie malnutrition on the concentration of protein A messenger RNA in surfactant of fetal rat lungs

The pulmonary surfactant is a lipoproteic complex that serves to lower surface tension at the air-liquid interface in the pulmonary alveoli. Approximately 2 to 4% of the pulmonary surfactant is constituted by the protein A (SP-A). The objective of the study was to determine the effects that maternal protein calorie malnutrition has on the fetal pulmonary growth and the production of SP-A messenger RNA in fetal rats. MATERIALS AND METHODS: Pregnant Sprague Dawley rats were divided into two groups, which received a diet with either 8% or 21% of proteins from gestational day 1 until the day 20. In this last day 11 fetuses were extracted by caesarean section and their lungs were removed to quantify the mRNA of the SP-A. First the mRNA was boosted using the technique of reverse transcriptase and polimerase chain reaction (RT-PCR) and then its concentration was determined by means of fluorodensitometry. RESULTS: There was a reduction in body weight and in wet lung weights of malnourished fetuses in comparison with the normal fetuses (5.03 +/- 0.20 g vs. 4.32 +/- 0.32 g, p < 0.05 and 79.0 +/- 3.8 mg vs. 146.0 +/- 3.4 mg, p < 0.05, respectively). The densitometric analysis of the SP-A mRNA concentration demonstrated a reduction of 32% in the malnourished fetuses (0.52 +/- 0.11 vs. 0.77 +/- 0.07, p < 0.05) compared with the normal fetuses. CONCLUSIONS: The maternal protein calorie malnutrition affected the pulmonary development and the synthesis of the SP-A mRNA. These data suggest that a defect occurrs at pre-transcriptional level that results in a diminution of the concentration of mRNA of SP-A in the neumocytes type II