High Expression of FOXO3 in Gastric Cancer Tissues is Associated with Poor Prognosis and Immune Cell Infiltration.

BACKGROUND: The purpose of this study was to explore the role of FOXO3 in gastric cancer (GC). METHODS: Data on gastric cancer and normal tissues were collected from the TCGA and GTEx databases. Survival analysis was performed with the Kaplan-Meier method, and the ENCORI online analysis tool was used to predict potential interaction miRNA. The MCPCOUNTER and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm were used to predict the relationship between immune infiltration and FOXO3. Finally, gene set enrichment analysis (GSEA) was used to explore the potential pathways of FOXO3 during the development of GC. RESULTS: We found that mRNA expression level of FOXO3 was remarkably higher in tumor tissue than in normal tissue, and poor prognoses of GC patients were correlated with higher expression of FOXO3. We also found that hsa-miR-18a-5p and hsa-miR-18b-5p can interact with FOXO3 and that high expression of hsa-miR-18a-5p and hsa-miR-18b-5p predicted better prognoses in GC patients. TP53 mutation was significantly associated with high FOXO3 expression, while ARID1A mutation was associated with low FOXO3 expression. Multiple immune cells were found to be related to the expression of FOXO3, and lower expression of FOXO3 may be better suited to immune checkpoint blockade treatment. CONCLUSIONS: We find that FOXO3 is a potential oncogene and that the transcript level of FOXO3 is related to the mutation of TP53 and ARID1A. In addition, FOXO3 may influence immune infiltration and different signal pathways through sponge adsorption of miRNA to impact the prognoses of stomach adenocarcinoma patients.

Effects of miR-384 and miR-134-5p Acting on YY1 Signaling Transduction on Biological Function of Gastric Cancer Cells.

OBJECTIVE: To explore the related influencing mechanism of miR-384 and miR-134-5p acting on Yin Yang 1 (YY1) signaling transduction on the biological function of gastric cancer (GC) cells. METHODS: miR-384, miR-134-5p and YY1 levels in human GC cell lines KATO III, MKN-45, SNU-1 and normal gastric cell line GES-1 were measured by polymerase chain reaction (PCR). Dual luciferase reporter (DLR) gene assay and Western blot (WB) were employed for correlation analysis between miR-384, miR-134-5p and YY1. miR-384-inhibitor, miR-384-mimics, empty plasmid (miRNA-NC) and sh-YY1 were transfected into KATO III cells. Cell proliferation was determined by 3-(4,5-Dimethylthiazolyl-2)-2,5-Diphenyl Tetrazolium Bromide (MTT), cell invasion was measured by Transwell, and apoptosis was analyzed by flow cytometry (FC). RESULTS: In KATO III, MKN-45 and SNU-1 cell lines, YY1 was upregulated while miR-384 and miR-134-5p were downregulated (P<0.001). The expression of miR-134-5p in the miR-134-5p-inhibitor group was significantly lower (P<0.001), while that in the miR-134-5p-mimics group was significantly higher (P<0.001). The expression of miR-384 in the miR-384-inhibitor group was significantly lower (P<0.001), and that in the miR-384-mimics group was significantly higher as compared to the NC group (P<0.001). Both miR-384 and miR-134-5p overexpression could inhibit cell proliferation and invasion, and promote apoptosis. As detected by WB, overexpressed miR-384 and miR-134-5p inhibited the expression of EMT-related molecular markers. Compared with sh-YY1, the number of cells in S phase decreased, the pro-apoptotic proteins boosted statistically, and the anti-apoptotic proteins declined notably after transfecting miR-134-5p-mimics/sh-YY1 or miR-384-mimics/sh-YY1 (P<0.05). The tumor growth rate of nude mice in miR-134-5p/sh-YY1 and miR-384/sh-YY1 groups were significantly lower than those in sh-YY1 group (all P<0.001). CONCLUSION: By targeting YY1 signaling transduction, miR-134-5p and miR-384 can alter the growth and apoptosis of GC cells, which are promising targets for new therapeutics of GC.

LncRNA LOC285194 modulates gastric carcinoma progression through activating Wnt/ß-catenin signaling pathway.

Emerging evidences have revealed long noncoding RNAs (lncRNAs') critical roles in diverse human carcinoma. Among these cancers, lncRNA LOC285194 has been extensively investigated in several types of carcinomas in the recent years. Nevertheless, the biological function, clinical relevance, and the influence of LOC285194 in gastric cancer (GC) are not fully understood. The present study aims to explore the biological function of LOC285194 in the progression and development of GC. First, LOC285194 expressions were detected in GC tissues and cell lines. The functional role of LOC285194 in GC was evaluated both in vitro and in vivo. Our data found that LOC285194 was lowly expressed both in human GC tissues and GC cell lines compared with corresponding normal controls. Moreover, LOC285194 was mitigated by transfection with LV-LOC285194 in both HGC-27 and MKN45 cell lines. Silencing of LOC285194 remarkably induced GC cell livability and cell proliferation. On the contrary, the LOC285194 overexpression suppressed MKN45 and HGC-27 cell proliferation and promoted cell apoptosis. Additionally, silencing of LOC285194 increased the ability of colony formation, cell migration, and invasive capacities, together with blocking the apoptotic rates of GC cells. Correspondently, LOC285194 overexpression exerted the opposite effects. Mechanistically, silencing of LOC285194 promoted GC progression via inducing Wnt signaling activity. Moreover, in vivo xenografts nude mice model results showed that LOC285194 inhibited GC progression through targeting Wnt signaling. Taken together, LOC285194 is associated with GC progression by regulating the Wnt signaling transduction, potentiating LOC285194's promising role as a novel treatment biomarker in GC.

Establishment of multiple diagnosis models for colorectal cancer with artificial neural networks.

The current study aimed to develop multiple diagnosis models for colorectal cancer (CRC) based on data from The Cancer Genome Atlas database and analysis with artificial neural networks in order to enhance CRC diagnosis methods. A genetic algorithm and mean impact value were used to select genes to be used as numerical encoded parameters to reflect cancer metastasis or aggression. Back propagation and learning vector quantization neural networks were used to build four diagnosis models: Cancer/Normal, M0/M1, carcinoembryonic antigen (CEA) <5/≥5 and Clinical stage I-II/III-IV. The performance of each model was evaluated by predictive accuracy (ACC), the area under the receiver operating characteristic curve (AUC) and a 10-fold cross-validation test. The ACC and AUC of the Cancer/Normal, M0/M1, CEA and Clinical stage models were 100%, 1.000; 87.14%, 0.670; 100%, 1.000; and 100%, 1.000, respectively. The 10-fold cross-validation test of the ACC values and sensitivity for each test were 93.75-99.39%, 1.0000; 80.58-88.24%, 0.9286-1.0000; 67.21-92.31%, 0.7091-1.0000; and 59.13-68.85%, 0.6017-0.6585, respectively. The diagnosis models developed in the current study combined gene expression profiling data and artificial intelligence algorithms to create tools for improved diagnosis of CRC.

[Comparison of long-term oncological outcomes of laparoscopic and open resection of rectal cancer].

OBJECTIVE: To compare the long-term oncological outcomes of laparoscopic and open resection of rectal cancers. METHODS: Between January, 2003 and December, 2008, 514 patients with rectal cancer were admitted in our hospital, among whom 186 underwent laparoscopic tumor resection and 238 received open radical resection of the tumors. The long-term survival of the patients and the recurrence pattern were compared between the two groups. RESULTS: The median follow-up of the patients was 48.54∓28.76 months. No significant differences were found between the two groups in the local recurrence rate (3.9% vs 5.5%, P=0.284), 5-year overall survival (69.4% vs 61.3%, P=0.067), or the 5-year disease-free survival rates (67.7% vs 60.7%, P=0.110). Both the 5-year overall survival and progression-free survival of the patients in stage IV were better in the laparoscopic group than in the open surgery group (P<0.05). CONCLUSION: Laparoscopic resection of rectal cancer can achieve long-term oncological outcomes comparable to those of conventional open surgery.