Clinical significance of circ-MTHFD2 in diagnosis, pathological staging and prognosis of NSCLC.

OBJECTIVE: To explore the clinical significance of circ-MTHFD2 in the diagnosis, pathological staging, and prognosis of non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 100 pairs of cancer tissues and adjacent tissues were surgically removed from NSCLC patients treated from July 2011 to January 2013 in our hospital were selected. All tissue samples were pathologically confirmed. Real Time-Polymerase Chain Reaction (qRT-PCR) was adopted to detect the expression of circ-MTHFD2 in NSCLC samples and its characteristic as a circular ribonucleic acid (circRNA). The receiver operating characteristic (ROC) curve was drawn to determine the diagnostic potential of circ-MTHFD2 in NSCLC. The relationship between circ-MTHFD2 expression and the clinical characteristics of NSCLC patients was analyzed by the χ2-test. Kaplan-Meier survival curves were depicted to assess the prognostic potential of circ-MTHFD2 in NSCLC. The effect of circ-MTHFD2 on the overall survival rate of NSCLC patients was uncovered by introducing the Cox proportional hazards model. RESULTS: The expression of circ-MTHFD2 in cancer tissues of NSCLC patients was higher than that in adjacent tissues (p<0.05), and there was no remarkable difference in the expression of circ-MTHFD2 before and after RNase R digestion (p>0.05). The area under the curve (AUC) of circ-MTHFD2 ROC was 0.701, with the cut-off value of 3.534, 90% sensitivity and 71% specificity. Circ-MTHFD2 expression was closely associated with smoking history, tumor size, tumor-node-metastasis (TNM) stage, lymph node metastasis, and recurrence in NSCLC patients (p<0.05). The prognosis of NSCLC patients with high expression of circ-MTHFD2 was evidently poorer than those with low expression. High expression of circ-MTHFD2 was an independent risk factor affecting the prognosis in NSCLC (p<0.05). CONCLUSIONS: The high expression of circ-MTHFD2 has clinical significance in the diagnosis, pathological staging, and prognosis of NSCLC.

[The 468th case: periodic fever, abdominal pain, small intestinal ulcers, NOD2 gene mutation].

Fever and abdominal pain are common symptoms and could be main manifestations in patients with autoinflammatory diseases. A 48-year-old female patient was admitted with recurrent fever and abdominal pain for 9 years. Serum level of inflammatory markers synchronously fluctuated with fever, and returned to normal when fever subsided. The periodic episodes of fever occurred every 1 to 4 months and failed to respond to empirical antibiotics. Whole exome sequencing showed heterozygous mutation of NOD2 gene q902k, leading to the final diagnosis of autoinflammatory disease. Corticosteroid and tripterygiumglycosides were effective for the disease remission.

Polymorphic microsatellite markers in the traditional Chinese medicinal plant Paris polyphylla var. yunnanensis.

Paris polyphylla var. yunnanensis is a traditional Chinese medicinal plant and is listed as vulnerable by the IUCN. This medicinal herb is well known for its analgesic and anti-inflammatory properties, most notably as an ingredient of the hemostatic compound "Yunnan Baiyao". However, over-exploitation of the plant for economic purposes is pushing the species to the brink of extinction. Therefore, there is an urgent need to develop conservation strategies for this endangered species, for example, through assessment of its genetic structure and diversity. Here, we developed ten novel polymorphic microsatellite loci. The characteristics of these markers were assessed in 60 individuals from South China. The number of alleles per locus ranged from 4 to 12, Observed and expected heterozygosity ranged from 0.303 to 0.969 and from 0.790 to 0.976, respectively. These markers will therefore be useful tools for future population genetic studies and for the conservation of genetic resources of P. polyphylla var. yunnanensis.

Lentivirus-mediated RASSF1A expression suppresses aggressive phenotypes of gastric cancer cells in vitro and in vivo.

Loss of Ras association domain family protein 1 isoform A (RASSF1A) expression is associated with the development of a variety of human cancers and the expression of carcinoembryonic antigen (CEA) frequently occurs in gastric cancer. This study investigated the effects of RASSF1A expression restoration using a hypoxia-inducible CEA promoter-driven vector on xenograft tumor growth in nude mice and on the in-vitro regulation of gastric cancer cell viability, cell cycle distribution, apoptosis, colony formation and invasion capacity. The data showed that the level of CEA mRNA and protein was much higher in gastric cancer SGC7901 cells than in a second gastric cancer cell line, MKN28, or in the MCF-10A normal epithelial breast cell line. RASSF1A expression was restored in SGC7901 cells compared with the negative control virus-infected SGC7910 cells. RASSF1A expression restoration significantly inhibited gastric cancer cell viability, colony formation and invasion capacity, but induced cell cycle arrest and apoptosis in vitro, especially under hypoxic culture conditions. At the gene level, restoration of RASSF1A expression under hypoxic culture conditions significantly suppressed matrix metalloproteinase-2 expression and prevented cyclinD1 expression. A nude mouse xenograft assay showed that the restoration of RASSF1A expression reduced gastric cancer xenograft formation and growth. In conclusion, the restoration of RASSF1A expression using a hypoxia-inducible and CEA promoter-driven vector suppressed aggressive phenotypes of gastric cancer cells in vitro and in vivo. These results suggest that LV-5HRE-CEAp-RASSF1A gene therapy may be a promising novel approach to treat advanced gastric cancer.