Increased Expression of POSTN Predicts Poor Prognosis: a Potential Therapeutic Target for Gastric Cancer.

BACKGROUND: Periostin (POSTN) is involved in many biological processes and is associated with the occurrence and development of several cancers, while its role in gastric cancer is not clear. We aimed to demonstrate the relationship between POSTN and gastric cancer based on publicly available data from The Cancer Genome Atlas (TCGA) database. METHODS: POSTN expression data and corresponding clinical information were downloaded from TCGA database. We compared the expression of POSTN in gastric cancer samples and normal samples. POSTN-related differentially expressed genes (DEGs) were identified for further functional enrichment analysis. In addition, the relationships between POSTN expression and clinicopathological features and survival in patients with gastric cancer were also investigated through univariate and multivariate Cox regression analyses. Furthermore, a nomogram was constructed to predict the survival probability of gastric cancer patients. RESULTS: POSTN expression in gastric cancer was significantly higher than that in normal gastric tissues (p < 0.001). High POSTN expression in gastric cancer was significantly related to poor prognostic features, including greater tumor extent (odds ratio [OR] = 1.638 for T3 and T4 vs. T1 and T2), worse histological type (OR = 0.329 for diffuse type vs. tubular type), and advanced histological grade (OR = 1.646 for grade 3 vs. grades 1 and 2) (all p < 0.05). The 118 identified DEGs were primarily enriched in pathways related to tumorigenesis and tumor progression, including the TGF-ß signaling pathway, the WNT signaling pathway, and the signaling by VEGF. POSTN expression was positively correlated with the enrichment of the macrophages (r = 0.599, p < 0.001), helper T2 cells (r = 0.146, p = 0.005), and CD8 + T cells (r = 0.190, p < 0.001), but negatively correlated with the enrichment of Th17 cells (r = - 0.130, p = 0.012) and NK CD56bright cells. Kaplan-Meier survival analysis showed that high POSTN expression is associated with a short overall survival (hazard ratio [HR] = 1.54; p = 0.011). In the multivariate cox regression analysis, high POSTN expression was confirmed to be an independent predictor of poor overall survival (HR = 1.681; p = 0.017). The constructed nomogram can well predict the 1 and 3 years overall survival probability of patients with GC (0.696 [95% CI, 0.671-0.721]). CONCLUSION: POSTN plays an important role in the progression and prognosis of gastric cancer, and it may serve as a useful biomarker to predict survival in gastric cancer patients.

Increased lncRNA AFAP1-AS1 expression predicts poor prognosis in gastric cancer: Evidence from published studies and followed up verification.

AIM: The purpose of this study was to clarify the influence of long non-coding RNA actin fiber-associated protein-1 antisense RNA 1 (lncRNA AFAP1-AS1) on the prognosis of gastric cancer (GC). METHODS: Based on meta-analysis, the association between the expression of AFAP1-AS1 and the prognosis of GC was estimated. GC tissue and non-cancer tissues from 136 patients were determined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and verified by Gene Expression Profiling Interactive Analysis (GEPIA). Kaplan-Meier and Cox proportional hazards models were conducted to analyze the correlation between AFAP1-AS1 expression and GC prognosis. RESULTS: The pooled analysis from five studies revealed that the AFAP1-AS1 expression was significantly associated with GC overall survival (hazard ratio (HR) = 2.49 and 95% confidence interval (95% CI): 2.02-3.08, p < 0.001). Compared with non-cancer tissues, AFAP1-AS1 expression level of GC tissues were significantly upregulated (p < 0.001), which was confirmed by the results of GEPIA. The area under the receiver-operating characteristic (ROC) curve was 0.893, and the high expression of AFAP1-AS1 was correlated with poor prognosis in patients with GC (p = 0.005). Clinical grade (HR = 1.912, 95% CI: 1.246-2.934, p = 0.003), pathologic tumor node metastasis (pTNM) (HR = 2.393, 95% CI: 1.431-4.033, p = 0.001), log odds of positive lymph nodes (LODDS) (HR = 2.910, 95% CI: 1.787-4.793, p < 0.001) and AFAP1-AS1 expression (HR = 2.393, 95% CI: 1.869-3.064, p < 0.001) were independent prognostic factors for GC revealed by multivariate Cox-regression analysis. CONCLUSION: This study demonstrated that the AFAP1-AS1 may be a novel biomarker for the diagnosis and prognosis of GC.

Corrigendum: LncRNA MSC-AS1 Is a Diagnostic Biomarker and Predicts Poor Prognosis in Patients With Gastric Cancer by Integrated Bioinformatics Analysis.

[This corrects the article DOI: 10.3389/fmed.2021.795427.].

LncRNA MSC-AS1 Is a Diagnostic Biomarker and Predicts Poor Prognosis in Patients With Gastric Cancer by Integrated Bioinformatics Analysis.

Numerous studies have shown that long uncoded RNA (lncRNA) MSC-AS1 may play an important role in the occurrence and development of some types of cancer. However, its role in gastric cancer has rarely been discussed. This study aimed to clarify the association between lncRNA MSC-AS1 and gastric cancer using The Cancer Genome Atlas (TCGA) database. We determined the expression of MSC-AS1 using the Wilcoxon rank sum test; in addition, logistic regression was applied to evaluate the association between MSC-AS1 and clinicopathological characteristics. Also, Kaplan-Meier and Cox regression were used to evaluate the relationship between MSC-AS1 and survival. A nomogram was conducted to predict the impact of MSC-AS1 on prognosis. Moreover, Gene Set enrichment analysis (GSEA) was performed to annotate the biological function of MSC-AS1. Quantitative analysis of immune infiltration was carried out by single-set GSEA (ssGSEA). The MSC-AS1 level was elevated in gastric cancer tissues. An increased MSC-AS1 level was significantly correlated with T stage (odds ratio [OR] = 2.55 for T3 and T4 vs. T1 and T2), histological type (OR = 5.28 for diffuse type vs. tubular type), histological grade (OR = 3.09 for grade 3 vs. grades 1 and 2), TP53 status (OR = 0.55 for mutated vs. wild type), and PIK3CA status (OR = 0.55 for mutated vs. wild type) (all p < 0.05) by univariate logistic regression. Kaplan-Meier survival analysis showed high MSC-AS1 expression had a poor overall survival [hazard ratio (HR) = 1.75; 95% confidence interval (CI): 1.25-2.45; p = 0.001] and progression-free interval (HR = 1.47; 95% CI: 1.03-2.10; p = 0.034). Multivariate survival analysis revealed that MSC-AS1 expression (HR = 1.681; 95% CI: 1.057-2.673; p = 0.028) was independently correlated with overall survival. GSEA demonstrated that the P38/MAPK pathway, the VEGF pathway, the cell adhesion molecules cams, the NOD-like receptor signaling pathway were differentially enriched in the high MSC-AS1 expression phenotype. SsGSEA and Spearman correlation revealed the relationships between MSC-AS1 and macrophages, NK cells, and Tems were the strongest. Coregulatory proteins were included in the PPI network. Upregulated lncRNA MSC-AS1 might be a potential biomarker for the diagnosis and prognosis of gastric cancer.

Various Kinds of Functional Digestive Tract Reconstruction Methods After Proximal Gastrectomy.

The incidence of proximal gastric cancer has shown a rising trend in recent years. Surgery is still the main way to cure proximal gastric cancer. Total gastrectomy with D2 lymph node dissection was considered to be the standard procedure for proximal gastric cancer in the past several decades. However, in recent years, many studies have confirmed that proximal gastrectomy can preserve part of the stomach function and can result in a better quality of life of the patient than total gastrectomy. Therefore, proximal gastrectomy is increasingly used in patients with proximal gastric cancer. Unfortunately, there are some concerns after proximal gastrectomy with traditional esophagogastrostomy. For example, the incidence of reflux esophagitis in patients who underwent proximal gastrectomy with traditional esophagogastrostomy is significantly higher than those patients who underwent total gastrectomy. To solve those problems, various functional digestive tract reconstruction methods after proximal gastrectomy have been proposed gradually. In order to provide some help for clinical treatment, in this article, we reviewed relevant literature and new clinical developments to compare various kinds of functional digestive tract reconstruction methods after proximal gastrectomy mainly from perioperative outcomes, postoperative quality of life and survival outcomes aspects. After comparison and discussion, we drew the conclusion that various functional reconstruction methods have their own advantages and disadvantages; large scale high-level clinical studies are needed to choose an ideal reconstruction method in the future. Besides, in clinical practice, surgeons should consider the condition of the patient for individualized selection of the most appropriate reconstruction method.

Laparoscopic-assisted versus open proximal gastrectomy with double-tract reconstruction for Siewert type II-III adenocarcinomas of esophago-gastric junction: a retrospective observational study of short-term outcomes.

BACKGROUND: Currently, the surgical approach to adenocarcinomas of esophago-gastric junction (AEG) remains controversial. Function-preserving gastric surgeries are becoming more popular, with proximal gastrectomy with double-tract anastomosis being one of the most important for AEG. Meanwhile, with the increasing use of laparoscopic techniques in the treatment of gastric cancer, the safety and effectiveness of laparoscopic-assisted proximal gastrectomy with double-tract anastomosis for Siewert type II-III AEG need to be further clarified. METHODS: Data of patients with Siewert type II/III AEG was collected at our center from October 2010 to December 2019 were retrospectively analyzed. 61 patients underwent open proximal gastrectomy with double-tract anastomosis (OPG-DT group) and 52 underwent laparoscopic-assisted proximal gastrectomy with double-tract anastomosis (LAPG-DT group). The clinical features, surgery, and short-term outcomes of patients in these 2 groups were collected to assess the safety and feasibility of LAPG-DT. RESULTS: A total of 113 patients were analyzed, there were 98 males and 15 females. No death during the operation. The differences in the number of lymph nodes, time to first flatus time to first eating, postoperative hospital stay, Additional analgesics were not statistically significant between two groups. Although the operative duration of LAPG-DT group was significantly longer than that of the OPG-DT group [(217±61) vs. (161±14) min, P=0.000), while less blood loss and less stress in LAPG-DT group. Early and late postoperative complications were similar between two groups. CONCLUSIONS: Although laparoscopic-assisted proximal gastrectomy with double-tract anastomosis requires long operative time, it is associated with less bleeding and milder stress. Therefore, it is a safe and feasible surgical method.

Forensic analysis on bursting accident of buffer tank in liquefied natural gas bus.

In December 2019, a buffer tank burst accident occurred in the maintenance of liquefied natural gas (LNG) bus in China. Failure analysis revealed the bus-mounted buffer tank had been subjected to an excessive internal pressurization, although the tank material met the specifications for engineering practice. The physical evidence related to the failed tank showed that a chemical explosion was impossible. As water was used to pouring the frozen pipeline prior to the accident, according to the consequences observed, the rapid phase transition (RPT) explosion of the residual LNG due to external heat from water was regarded as the main causation of incident. The explosion energy was inversely estimated by the TNT equivalent method, and the rapid expansion of natural gas produced excessive pressure, thus causing the buffer tank to explode.

Short-term outcomes of laparoscopic versus open proximal gastrectomy with double-tract reconstruction for Siewert type II and III adenocarcinoma of the esophagogastric junction: a retrospective observational study of consecutive patients.

BACKGROUND: To investigate the safety and merits of laparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DT) for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). METHODS: Retrospective analysis of the clinical data of 100 consecutive patients with Siewert II and III AEG treated at the Affiliated Tumor Hospital of Zhengzhou University from October 2010 to October 2019 was performed. Out of these patients, 69 underwent open proximal gastrectomy with double-tract reconstruction (OPG-DT), while 31 underwent LPG-DT. The clinicopathological characteristics, perioperative data, and short-term outcomes of the two groups were compared. A P value <0.05 was considered statistically significant. RESULTS: Males accounted for 87% of all patients. Lymph nodes (LNs) count, time to first meal, postoperative length of stay, and postoperative complications were similar between the OPG-DT and LPG-DT group. flatus time was significantly shorter in the LPG-DT group (P<0.05), while the duration of operation was significantly shorter in the the OPG-DT group (P<0.001). Furthermore, the LPG-DT group has less blood loss, shorter flatus time, and lower postoperative-day-5 white blood cell (WBC) count and C-reactive protein (CRP) levels (P<0.05). CONCLUSIONS: Although LPG-DT took longer to perform, its advantages of reduced blood loss and less surgical stress reflected on inflammatory markers supports an acceptable surgical option for Siewert II and III AEG.

Which is the optimal management for locally advanced gastric cancer patients with TRG 0 and 1 after R0 resection?

BACKGROUND: Neoadjuvant chemotherapy (NAC) followed by surgery currently offers promise as a strategy for patients with locally advanced gastric cancer (GC). However, there is limited evidence to guide treatment for TRG 0 and 1 patients with locally advanced GC after R0 resection. This study set out to explore the optimal management for TRG 0 and 1 patients with locally advanced GC after R0 resection. METHODS: The retrospective data of 154 TRG 0 and 1 patients with locally advanced GC following R0 resection who were treated between January 2012 and December 2018 were collected and analyzed. The Kaplan-Meier method was used to estimate the survival rate. Multivariate analysis was performed using the Cox proportional hazards model. RESULTS: The median follow-up was 34.1 (range, 6.6-90.9) months. Six patients (3.9%) were lost during follow-up. Of the 27 patients who experienced relapse, 12 died, including 2 patients who died of non-neoplastic causes. The 5-year recurrence-free survival (RFS) and 5-year overall survival (OS) were 71.6% (95% CI: 68.5-79.6) and 82.9% (95% CI: 76.9-86.1) for the whole cohort, respectively. Univariate analysis revealed that patients with carcinoembryonic antigen (CEA) <5.0 ng/ml after NAC (77.7% vs. 20.1%, P<0.001), distal gastrectomy (91.7% vs. 67.5%, P=0.046) had higher 5-year RFS. Meanwhile, combined resection (55.6% vs. 73.1%, P=0.042), major complications (42.7% vs. 80.50%, P<0.001), and lymph node metastasis (ypN+) (52.0% vs. 83.7%, P<0.001) had lower 5-year RFS. The multivariate analysis showed that CEA level after NAC (HR =2.876, 95% CI: 1.051-7.872, P=0.040), major complications (HR =2.432, 95% CI: 1.062-5.567, P=0.035), and lymph node metastasis (ypN+) (HR =3.183, 95% CI: 1.242-8.161, P=0.016) were independent prognostic factors. CONCLUSIONS: TRG 0 and 1 patients with local GC after R0 resection following NAC had a good prognosis, especially patients with CEA <5.0 ng/mL after NAC, and those without major complications or lymph node metastasis. Monotherapy or no chemotherapy may offer options for treating TRG 0 and 1 patients without adverse prognostic factors.

Short and long-term outcomes after proximal gastrectomy with double tract reconstruction for Siewert type III adenocarcinoma of the esophagogastric junction: a propensity score matching study from a 10-year experience in a high-volume hospital.

BACKGROUND: Total gastrectomy and proximal gastrectomy (PG) are both surgical options for the treatment of Siewert type III adenocarcinoma of the esophagogastric junction (AEG). Currently there is no consensus on selecting which procedure to perform; in particular, there are few reports of long-term outcomes for patients with local advanced AEG. The aim of this study was to validate the usefulness of PG with double-tract reconstruction in Siewert type III AEG. METHODS: The clinical data of patients with Siewert type III AEG underwent PG with double-tract reconstruction (PG-DT) or total gastrectomy with Roux-en-Y anastomosis (TG-RY) at our hospital between October 2010 and October 2018. According to the defined inclusion and exclusion criteria, 2,146 cases were enrolled in this study. A 1-to-1 propensity score matching (PSM) was performed to compare the short and long-term outcomes between the 2 groups. RESULTS: The operation time was longer in the PG-DT group, and the proportion rates of complications and recovery time was similar in the 2 groups. The rates of maintaining bodyweight and free-fat mass index were significantly higher in patients who underwent PG-DT compared to those who underwent TG-RY. While complications, recovery time and survival are similar between two groups. CONCLUSIONS: Regarding short-term outcomes, PG-DT seemed to be superior in terms of maintaining body weight and skeletal muscle compared to TG-RY, while both had similar complications. It was found that PG-DT enabled a potentially longer survival of pathological stage II and III Siewert type III AEG, although the finding was statistically insignificant. These results may help surgeons to determine the appropriate surgical approach and strategy for patients with early and locally advanced Siewert type III AEG.

Knockdown of lncRNA GHET1 inhibits osteosarcoma cells proliferation, invasion, migration and EMT in vitro and in vivo.

OBJECTIVE: Osteosarcoma is the most common primary malignant skeleton tumor that derives from mesenchymal cells. Emerging evidences have identified the vital role of long non-coding RNAs (lncRNAs) in the development of osteosarcoma. In this study, we aimed to investigate the role of lncRNA gastric carcinoma highly expressed transcript 1 (GHET1) in osteosarcoma progression. METHODS: The expression levels of relevant genes in clinical samples and cell lines were determined by quantitative real-time PCR. Cell proliferation was determined by CCK8 and cell colony formation assays. Transwell assay was used to detect the invasion and migration of osteosarcoma cells. Cell apoptosis and cell cycle were detected by flow cytometry. Protein levels were detected by western blot. In vivo tumor growth was investigated in the xenograft nude mice model. To determine whether growth inhibition and apoptosis are responsible for antitumor activity of silencing GHET1, immunohistochemistry for proliferation and TUNEL assay was performed in xenograft tissues. In vivo lung metastasis was performed to detect the effect of GHET1 on cell metastasis ability. RESULTS: Our results revealed that GHET1 was up-regulated in osteosarcoma tissues compared to normal tissues. GHET1 was also increased in osteosarcoma cell lines compared to normal osteoplastic cell line. The up-regulation of GHET1 was significantly associated with TNM stage, distant metastasis and lymph node metastasis in patients with osteosarcoma. In vitro studies showed that silencing GHET1 in MG-63 and U2OS cells inhibited cell proliferation, cell invasion and migration and epithelial-to-mesenchymal transition (EMT), promoted cell apoptotic rate, and also caused an increase in cell population at G0/G1 phase with a decrease in cell population at S phase. Overexpression of GHET1 promoted the proliferation, invasion and migration of osteosarcoma cells. Importantly, silencing GHET1 inhibited tumor growth and tumor metastasis in mice MG-63-xenograft model in association with changes of EMT-related genes, reduced expression of Ki-67 and promotion of apoptosis. CONCLUSION: GHET1 was up-regulated in osteosarcoma tissues and cell lines, inhibited cell apoptosis, promoted cell proliferation, invasion and migration by affecting EMT in vitro, and was correlated with the tumor growth and metastasis in vivo. GHET1 may be a potential therapeutic target of osteosarcoma treatment.