Expression and significance of mi R-654-5p and mi R-376b-3p in patients with colon cancer

BACKGROUND The relationship between micro RNAs,such as miR-654-5 p and miR-376 b-3 p,and the prognosis of colon cancer has not been studied until now.AIM To evaluate the expression levels of miR-654-5 p and miR-376 b-3 p and their clinical significance in colon cancer.METHODS RT-q PCR was performed to evaluate miR-654-5 p and miR-376 b-3 p expression in34 pairs of colon cancer and adjacent noncancerous tissues.Subsequently,the association of miR-654-5 p and miR-376 b-3 p expression with clinical factors or the survival of patients suffering from colon cancer was determined by using The Cancer Genome Atlas.RESULTS miR-654-5 p was upregulated and miR-376 b-3 p was downregulated in colon cancer tissues compared with adjacent noncancerous tissues(P<0.001).Increased miR-654-5 p and decreased miR-376 b-3 p expression levels weresignificantly associated with metastasis and clinical stage.Moreover,a univariate analysis demonstrated that colon cancer patients with high miR-654-5 p or low miR-376 b-3 p expression(P=0.044 and 0.007,respectively)had a poor overall survival rate.A multivariate analysis identified high miR-654-5 p expression and low miR-376 b-3 p expression as independent predictors of poor survival in colon cancer patients.CONCLUSION Upregulated miR-654-5 p and downregulated miR-376 b-3 p may be associated with tumour progression in colon cancer,and these micro RNAs may serve as independent prognostic markers for colon cancer.

Prognostic factors of primary gastrointestinal stromal tumors： a cohort study based on high-volume centers

Objective： We aimed to evaluate the clinicopathologic characteristics, immunohistochemical expression and prognostic factors of patients with primary gastrointestinal stromal tumors（GISTs）.Methods： Data from 2,570 consecutive GIST patients from four medical centers in China（January2001–December 2015） were reviewed. Survival curves were constructed by the Kaplan-Meier method, and Cox regression models were used to identify independent prognostic factors.Results： Of the included patients, 1,375（53.5%） were male, and the patient age range was 18 to 95（median, 58）years. The tumors were mostly found in the stomach（64.5%）, small intestine（25.1%） and colorectal region（5.1%）.At the time of diagnosis, the median tumor size was 4.0（range： 0.1–55.0） cm, and the median mitotic index per 50 high power fields（HPFs） was 3（range： 0–254）. Of the 2,168 resected patients, 2,009（92.7%） received curative resection. According to the modified National Institutes of Health（NIH） classification, 21.9%, 28.9%, 14.1% and35.1% were very low-, low-, intermediate-and high-risk tumors, respectively. The rate of positivity was 96.4% for c-Kit, 87.1% for CD34, 96.9% for delay of germination 1（DOG-1）, 8.0% for S-100, 31.0% for smooth muscle actin（SMA） and 5.1% for desmin. However, the prognostic value of each was limited. Multivariate analysis showed that age, tumor size, mitotic index, tumor site, occurrence of curative resection and postoperative imatinib were independent prognostic factors. Furthermore, we found that high-risk patients benefited significantly from postoperative imatinib（P〈0.001）, whereas intermediate-risk patients did not（P=0.954）.Conclusions： Age, tumor size, mitotic index, tumor site, occurrence of curative resection and postoperative imatinib were independent prognostic factors in patients with GISTs. Moreover, determining whether intermediate-risk patients can benefit from adjuvant imatinib would be of considerable interest in future studies.

Detection and Clinical Significance of DLC1 Gene Methylation in Serum DNA from Colorectal Cancer Patients

Objective: Deleted in liver cancer 1 (DLC1) is a new candidate tumor suppressor gene, whose down-regulation or even silence will result from promoter hypermethylation in various human cancers including colorectal cancer (CRC). The aim of this study is to evaluate the diagnostic role of DLC1 gene methylation in the serum DNA from CRC patients. Methods: This study enrolled 85 CRC patients and 45 patients with benign colorectal diseases. Methylation-specific polymerase chain reaction (MSP) was used to determine the promoter methylation status of DLC1 gene in serum DNA. The combination of DLC1 methylation and conventional tumor markers was further analyzed. Results: Hypermethylation of DLC1 was detected in 42.4% (36/85) of CRC serums, while seldom in the benign controls (8.9%, 4/45) (P<0.001). The aberrant DLC1 methylation in serum DNA was not associated with patients’ clinicopathological features and elevated CEA/CA19-9 levels. Furthermore, the combinational analysis of CEA, CA19-9 and DLC1 methylation showed a higher sensitivity and no reduced diagnostic specificity than CEA and CA19-9 combination for CRC diagnosis. Conclusion: The serum DLC1 methylation may be a promising biomarker for the early detection of CRC, which will further increase the diagnostic efficiency in combination with CEA and CA19-9.

Characteristic gene expression profiles in the progression from normal gastric epithelial cells to moderate gastric epithelial dysplasia and to gastric cancer

Background Gastric cancer ranks high among the most common causes of cancer-related death worldwide. This study was designed to explore key genes involved in the progression of normal gastric epithelial cells to moderate gastric epithelial dysplasia （mGED） and to gastric cancer. Methods Twelve pairs of mGED tissues, gastric cancer tissues, and normal gastric tissues were collected by gastroscopy. Total RNA was then extracted and purified. After the addition of fluorescent tags, hybridization was carried out on a Gene chip microarray slide. Significance analysis of microarrays was performed to determine significant differences in gene expression between the different tissue types. Results Microarray data analysis revealed totally 34 genes that were expressed differently： 18 highly expressed （fold change 〉2; P 〈0.01） and 16 down-regulated （fold change 〉2; P 〈0.01）. Of the 34 genes, 24 belonged to several different functional categories such as structural molecule activity, extracellular regions, structural formation, cell death, biological adhesion, developmental processes, locomotion, and biological regulation that were associated with cancer. The remaining 10 genes were not involved in cancer research. Of these genes, the expression levels of Matrix metalloproteinase-12 （MMP12）, Caspase-associated recruitment domain 14 （CARD14）, and Chitinase 3-like 1 （CHI3L1） were confirmed by semi-quantitative RT-PCR. A two-way clustering algorithm divided the 36 samples into three categories and the overall correct classification efficiency was 80.6% （29/36）. Almost all of these genes （31/34） showed constant changes in the process of normal gastric epithelial cells to mGED to gastric cancer. Conclusions The results of this study provided global gene expression profiles during the development and progression from normal gastric epithelial cells to mGED to gastric cancer. These data may provide new insights into the molecular pathology of gastric cancer which may be useful for the detection, diagnosis, and treatment.

Correlation between dynamic contrast-enhanced MRI and histopathology in the measurement of tumor and breast volume and their ratio in breast cancer patients： a prospective study

Background Earlier studies have examined the association between the diameter of primary tumors measured by magnetic resonance imaging （MRI） and histopathology in breast cancer patients. However, the diameter does not completely describe the dimensions of the breast tumor or its volumetric proportion relative to the whole breast. The association between breast tumor volume/breast volume ratios measured by these two techniques has not been reported.

The molecular mechanisms supporting the homeostasis and activation of dendritic epidermal T cell and its role in promoting wound healing

The epidermis is the outermost layer of skin and the first barrier against invasion.Dendritic epidermal T cells(DETCs)are a subset ofT cells and an important component of the epidermal immune microenvironment.DETCs are involved in skin wound healing,malignancy and autoim-mune diseases.DETCs secrete insulin-like growth factor-1 and keratinocyte growth factor for skin homeostasis and re-epithelization and release inflammatory factors to adjust the inflammatory microenvironment of wound healing.Therefore,an understanding of their development,activation and correlative signalling pathways is indispensable for the regulation of DETCs to accelerate wound healing.Our review focuses on the above-mentioned molecular mechanisms to provide a general research framework to regulate and control the function of DETCs.