LncRNA NEAT1 promotes gastric cancer progression via miR-1294/AKT1 axis.

Long non-coding RNAs (lncRNAs) were reported to promote the development of gastric cancer (GC). Nuclear-enriched abundant transcript 1 (NEAT1) played a great role in diverse cancers, but the mechanism of NEAT1 in GC remains indistinct. NEAT1 and AKT1 were distinctly up-regulated and miR-1294 was down-regulated in GC tissues and cells. Cell proliferation and metastasis were refrained but apoptosis was promoted in GC cells after knockdown of NEAT1. NEAT1 negatively regulated miR-1294 expression, and the miR-1294 inhibitor reverted the si-NEAT1-induced effect on GC cells. NEAT1 modulated AKT1 expression through miR-1294, and the si-NEAT1-induced effect was relieved by AKT1. NEAT1 affected phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway via regulating miR-1294 and AKT1. NEAT1 could modulate cell proliferation, apoptosis, and metastasis in GC cells by regulating the PI3K/AKT/mTOR signaling pathway via the miR-1294/AKT1 axis, showing the great potential for NEAT1 as a valid biomarker in the progression and treatment of GC.

Association between PIK3CA alteration and prognosis of gastric cancer patients: a meta-analysis.

BACKGROUND: Increasing evidence suggests that dysregulation of phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) plays an important role in carcinogenesis. However, the relationship between PIK3CA expression and gastric cancer (GC) prognosis remains controversial. METHODS: We searchedPubMed, Embase, Web of Science, and the Cochrane Library databases for relevant studies up to June 30, 2017. Primary outcomes were hazard ratio (HR), odds ratio (OR), and 95% confidence intervals (CI) for association with overall survival and clinicopathological features. RESULTS: Eleven studies comprising 2481 GC patients were analyzed. Pooled analysis showed that PIK3CA upregulation was significantly associated with worse overall survival (HR = 1.79, 95% CI 1.42-2.27, p< 0.001) at the protein (HR = 1.94, 95% CI 1.52-2.47, p< 0.001) but not the gene (HR = 1.57, 95% CI 0.92-2.69, p= 0.097) level. PIK3CA gene mutation did not correlate with overall survival (HR = 1.05, 95% CI 0.83-1.34, p= 0.666) but was significantly associated with poor tumor differentiation (OR = 0.37, 95% CI 0.17-0.76, p= 0.011). CONCLUSION: High PIK3CA protein expression predicted poor prognosis in GC, whereas PIK3CA gene amplification or mutation did not. Moreover, PIK3CA mutation was an indicator of poorly differentiated tumors.

Feasibility study on expanded indication for endoscopic submucosal dissection of intramucosal poorly differentiated early gastric cancer.

AIM: To identify clinicopathological factors predictive of lymph node metastasis (LNM) in intramucosal poorly differentiated early gastric cancer (EGC), and further to expand the possibility of using endoscopic submucosal dissection (ESD) for the treatment of intramucosal poorly differentiated EGC. METHODS: Data for 81 surgically treated patients with intramucosal poorly differentiated EGC were collected, and the association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Several clinicopathologic factors were investigated to identify predictive factors for lymph nodes metastasis, including gender, age, family history of gastric cancer, number of tumors, tumor location, ulceration, tumor size, macroscopic type, lymphatic vessel involvement, and signet-ring-cell component. RESULTS: Tumor size (OR = 7.273, 95%CI: 1.246-29.918, P = 0.042), lymphatic vessel involvement (OR = 42.219, 95%CI: 1.923-97.052, P = 0.018) and signet-ring-cell component (OR = 17.513, 95%CI: 1.647-77.469, P = 0.034) that were significantly associated with LNM by univariate analysis, were found to be significant and independent risk factors for LNM by multivariate analysis. However, gender, age, family history of gastric cancer, number, location, ulceration and macroscopic type of tumor were found not to be associated with LNM. Of these 81 patients diagnosed with intramucosal poorly differentiated EGC, 7 (8.6%) had LNM. The LNM rates were 9.1%, 22.2% and 57.1%, respectively, in cases with one, two and three of the risk factors. There was no LNM in 54 patients without the three risk clinicopathological factors. CONCLUSION: Tumor size, lymphatic vessel involvement and signet-ring-cell component are independently associated with the presence of LNM in intramucosal poorly differentiated EGC. Thus, these three risk factors may be used as a simple criterion to expand the possibility of using ESD for the treatment of intramucosal poorly differentiated EGC.

Risk clinicopathological factors for lymph node metastasis in poorly differentiated early gastric cancer and their impact on laparoscopic wedge resection.

AIM: To investigate the predictive factors of lymph node metastasis (LNM) in poorly differentiated early gastric cancer (EGC), and enlarge the possibility of using laparoscopic wedge resection (LWR). METHODS: We retrospectively analyzed 85 patients with poorly differentiated EGC who underwent surgical resection between January 1992 and December 2010. The association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. Odds ratios (OR) with 95%CI were calculated. We further examined the relationship between the positive number of the three significant predictive factors and the LNM rate. RESULTS: In the univariate analysis, tumor size (P = 0.011), depth of invasion (P = 0.007) and lymphatic vessel involvement (P < 0.001) were significantly associated with a higher rate of LNM. In the multivariate model, tumor size (OR = 7.125, 95%CI: 1.251-38.218, P = 0.041), depth of invasion (OR = 16.624, 95%CI: 1.571-82.134, P = 0.036) and lymphatic vessel involvement (OR = 39.112, 95%CI: 1.745-123.671, P = 0.011) were found to be independently risk clinicopathological factors for LNM. Of the 85 patients diagnosed with poorly differentiated EGC, 12 (14.1%) had LNM. The LNM rates were 5.7%, 42.9% and 57.1%, respectively in cases with one, two and three of the risk factors respectively in poorly differentiated EGC. There was no LNM in 29 patients without the three risk clinicopathological factors. CONCLUSION: LWR alone may be sufficient treatment for intramucosal poorly differentiated EGC if the tumor is less than or equal to 2.0 cm in size, and when lymphatic vessel involvement is absent at postoperative histological examination.

Defining a subgroup treatable for laparoscopic surgery in poorly differentiated early gastric cancer: the role of lymph node metastasis.

OBJECTIVE: The present study aims to identify the clinicopathologic factors predictive of lymph node metastasis (LNM) in poorly differentiated early gastric cancer (EGC) and to expand the possibility of using laparoscopic surgery for the treatment of poorly differentiated EGC. METHODS: Data from 70 cases of poorly differentiated EGC treated with surgery were collected. The association between clinicopathologic factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. RESULTS: Univariate analysis showed that tumor size, depth of invasion, and lymphatic vessel involvement (LVI) were the significant and independent risk factors for LNM (all P<0.05). The LNM rates were 6.9%, 45.5%, and 60.0%, respectively. There was no LNM in 25 patients without the above three risk factors. CONCLUSIONS: Laparoscopic surgery is a sufficient treatment for intramucosal poorly differentiated EGC if the tumor is less than or equal to 2.0 cm in size and when LVI is absent upon postoperative histological examination.