Metaplastic regeneration in the mouse stomach requires a reactive oxygen species pathway.

In pyloric metaplasia, mature gastric chief cells reprogram via an evolutionarily conserved process termed paligenosis to re-enter the cell cycle and become spasmolytic polypeptide-expressing metaplasia (SPEM) cells. Here, we use single-cell RNA sequencing (scRNA-seq) following injury to the murine stomach to analyze mechanisms governing paligenosis at high resolution. Injury causes induced reactive oxygen species (ROS) with coordinated changes in mitochondrial activity and cellular metabolism, requiring the transcriptional mitochondrial regulator Ppargc1a (Pgc1α) and ROS regulator Nf2el2 (Nrf2). Loss of the ROS and mitochondrial control in Ppargc1a-/- mice causes the death of paligenotic cells through ferroptosis. Blocking the cystine transporter SLC7A11(xCT), which is critical in lipid radical detoxification through glutathione peroxidase 4 (GPX4), also increases ferroptosis. Finally, we show that PGC1α-mediated ROS and mitochondrial changes also underlie the paligenosis of pancreatic acinar cells. Altogether, the results detail how metabolic and mitochondrial changes are necessary for injury response, regeneration, and metaplasia in the stomach.

Gastric intestinal metaplasia: progress and remaining challenges.

Most gastric cancers arise in the setting of chronic inflammation which alters gland organization, such that acid-pumping parietal cells are lost, and remaining cells undergo metaplastic change in differentiation patterns. From a basic science perspective, recent progress has been made in understanding how atrophy and initial pyloric metaplasia occur. However, pathologists and cancer biologists have long been focused on the development of intestinal metaplasia patterns in this setting. Arguably, much less progress has been made in understanding the mechanisms that lead to the intestinalization seen in chronic atrophic gastritis and pyloric metaplasia. One plausible explanation for this disparity lies in the notable absence of reliable and reproducible small animal models within the field, which would facilitate the investigation of the mechanisms underlying the development of gastric intestinal metaplasia (GIM). This review offers an in-depth exploration of the current state of research in GIM, shedding light on its pivotal role in tumorigenesis. We delve into the histological subtypes of GIM and explore their respective associations with tumor formation. We present the current repertoire of biomarkers utilized to delineate the origins and progression of GIM and provide a comprehensive survey of the available, albeit limited, mouse lines employed for modeling GIM and engage in a discussion regarding potential cell lineages that serve as the origins of GIM. Finally, we expound upon the myriad signaling pathways recognized for their activity in GIM and posit on their potential overlap and interactions that contribute to the ultimate manifestation of the disease phenotype. Through our exhaustive review of the progression from gastric disease to GIM, we aim to establish the groundwork for future research endeavors dedicated to elucidating the etiology of GIM and developing strategies for its prevention and treatment, considering its potential precancerous nature.

Single-cell sequencing of ascites fluid illustrates heterogeneity and therapy-induced evolution during gastric cancer peritoneal metastasis.

Peritoneal metastasis is the leading cause of death for gastrointestinal cancers. The native and therapy-induced ascites ecosystems are not fully understood. Here, we characterize single-cell transcriptomes of 191,987 ascites cancer/immune cells from 35 patients with/without gastric cancer peritoneal metastasis (GCPM). During GCPM progression, an increase is seen of monocyte-like dendritic cells (DCs) that are pro-angiogenic with reduced antigen-presenting capacity and correlate with poor gastric cancer (GC) prognosis. We also describe the evolution of monocyte-like DCs and regulatory and proliferative T cells following therapy. Moreover, we track GC evolution, identifying high-plasticity GC clusters that exhibit a propensity to shift to a high-proliferative phenotype. Transitions occur via the recently described, autophagy-dependent plasticity program, paligenosis. Two autophagy-related genes (MARCKS and TXNIP) mark high-plasticity GC with poorer prognosis, and autophagy inhibitors induce apoptosis in patient-derived organoids. Our findings provide insights into the developmental trajectories of cancer/immune cells underlying GCPM progression and therapy resistance.

The Efficacy and Safety of Celecoxib in Addition to Standard Cancer Therapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The purpose of this meta-analysis was to evaluate the efficacy and safety of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, in addition to standard anticancer therapy. Randomized controlled trials (RCTs) that evaluated the efficacy and safety of celecoxib-combined cancer therapy were systematically searched in PubMed and Embase databases. The endpoints were overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), objective response rate (ORR), disease control rate (DCR), pathological complete response (pCR), and adverse events (AEs). The results of 30 RCTs containing 9655 patients showed limited benefits in celecoxib-combined cancer therapy. However, celecoxib-combined palliative therapy prolonged PFS in epidermal growth factor receptor (EGFR) wild-type patients (HR = 0.57, 95%CI = 0.35-0.94). Moreover, despite a slight increase in thrombocytopenia (RR = 1.35, 95%CI = 1.08-1.69), there was no increase in other toxicities. Celecoxib combined with adjuvant therapy indicated a better OS (HR = 0.850, 95%CI = 0.725-0.996). Furthermore, celecoxib plus neoadjuvant therapy improved the ORR in standard cancer therapy, especially neoadjuvant therapy (overall: RR = 1.13, 95%CI = 1.03-1.23; neoadjuvant therapy: RR = 1.25, 95%CI = 1.09-1.44), but not pCR. Our study indicated that adding celecoxib to palliative therapy prolongs the PFS of EGFR wild-type patients, with good safety profiles. Celecoxib combined with adjuvant therapy prolongs OS, and celecoxib plus neoadjuvant therapy improves the ORR. Thus, celecoxib-combined cancer therapy may be a promising therapy strategy.

DDIT4 Licenses Only Healthy Cells to Proliferate During Injury-induced Metaplasia.

BACKGROUND AND AIMS: In stomach, metaplasia can arise from differentiated chief cells that become mitotic via paligenosis, a stepwise program. In paligenosis, mitosis initiation requires reactivation of the cellular energy hub mTORC1 after initial mTORC1 suppression by DNA damage induced transcript 4 (DDIT4 aka REDD1). Here, we use DDIT4-deficient mice and human cells to study how metaplasia increases tumorigenesis risk. METHODS: A tissue microarray of human gastric tissue specimens was analyzed by immunohistochemistry for DDIT4. C57BL/6 mice were administered combinations of intraperitoneal injections of high-dose tamoxifen (TAM) to induce spasmolytic polypeptide-expressing metaplasia (SPEM) and rapamycin to block mTORC1 activity, and N-methyl-N-nitrosourea (MNU) in drinking water to induce spontaneous gastric tumors. Stomachs were analyzed for proliferation, DNA damage, and tumor formation. CRISPR/Cas9-generated DDIT4-/- and control human gastric cells were analyzed for growth in vitro and in xenografts with and without 5-fluorouracil (5-FU) treatment. RESULTS: DDIT4 was expressed in normal gastric chief cells in mice and humans and decreased as chief cells became metaplastic. Paligenotic Ddit4-/- chief cells maintained constitutively high mTORC1, causing increased mitosis of metaplastic cells despite DNA damage. Lower DDIT4 expression correlated with longer survival of patients with gastric cancer. 5-FU-treated DDIT4-/- human gastric epithelial cells had significantly increased cells entering mitosis despite DNA damage and increased proliferation in vitro and in xenografts. MNU-treated Ddit4-/- mice had increased spontaneous tumorigenesis after multiple rounds of paligenosis induced by TAM. CONCLUSIONS: During injury-induced metaplastic proliferation, failure of licensing mTORC1 reactivation correlates with increased proliferation of cells harboring DNA damage, as well as increased tumor formation and growth in mice and humans.

A Dedicated Evolutionarily Conserved Molecular Network Licenses Differentiated Cells to Return to the Cell Cycle.

Differentiated cells can re-enter the cell cycle to repair tissue damage via a series of discrete morphological and molecular stages coordinated by the cellular energetics regulator mTORC1. We previously proposed the term "paligenosis" to describe this conserved cellular regeneration program. Here, we detail a molecular network regulating mTORC1 during paligenosis in both mouse pancreatic acinar and gastric chief cells. DDIT4 initially suppresses mTORC1 to induce autodegradation of differentiated cell components and damaged organelles. Later in paligenosis, IFRD1 suppresses p53 accumulation. Ifrd1-/- cells do not complete paligenosis because persistent p53 prevents mTORC1 reactivation and cell proliferation. Ddit4-/- cells never suppress mTORC1 and bypass the IFRD1 checkpoint on proliferation. Previous reports and our current data implicate DDIT4/IFRD1 in governing paligenosis in multiple organs and species. Thus, we propose that an evolutionarily conserved, dedicated molecular network has evolved to allow differentiated cells to re-enter the cell cycle (i.e., undergo paligenosis) after tissue injury. VIDEO ABSTRACT.

Efficacy of immune checkpoint inhibitors and age in cancer patients.

Aim: To evaluate the impact of age on the efficacy of immune checkpoint inhibitors (ICI) in cancer patients. Materials & methods: The primary outcomes included overall survival (OS) and progression-free survival (PFS). Subgroup, meta-regression analysis and within-trial interaction HR were conducted. Results: A total of 34 studies containing 20,511 cancer patients were included. ICI could improve the OS and PFS in patient aged <65 and ≥65 years. Patients aged <75 years treated with ICI also had favorable OS and PFS compared with the control groups. Conclusion: ICI has comparable efficacy in cancer patients aged <65 and ≥65 years. Cancer patients aged ≥75 years need more attention in the future clinical trials.

A Metformin-Responsive Metabolic Pathway Controls Distinct Steps in Gastric Progenitor Fate Decisions and Maturation.

Cellular metabolism plays important functions in dictating stem cell behaviors, although its role in stomach epithelial homeostasis has not been evaluated in depth. Here, we show that the energy sensor AMP kinase (AMPK) governs gastric epithelial progenitor differentiation. Administering the AMPK activator metformin decreases epithelial progenitor proliferation and increases acid-secreting parietal cells (PCs) in mice and organoids. AMPK activation targets Krüppel-like factor 4 (KLF4), known to govern progenitor proliferation and PC fate choice, and PGC1α, which we show controls PC maturation after their specification. PC-specific deletion of AMPKα or PGC1α causes defective PC maturation, which could not be rescued by metformin. However, metformin treatment still increases KLF4 levels and suppresses progenitor proliferation. Thus, AMPK activates KLF4 in progenitors to reduce self-renewal and promote PC fate, whereas AMPK-PGC1α activation within the PC lineage promotes maturation, providing a potential suggestion for why metformin increases acid secretion and reduces gastric cancer risk in humans.

Antibiotic use and the efficacy of immune checkpoint inhibitors in cancer patients: a pooled analysis of 2740 cancer patients.

The gut microbiota plays a critical role in the anti-tumor immune response. There is increasing data showing that antibiotics (ATBs) change the composition of the gut microbiota and affect the efficacy of immune checkpoint inhibitors (ICIs). However, this is the first meta-analysis to evaluate the association between ATB use and ICI efficacy in cancer patients to provide a better understanding of the strength of this association. We performed a literature search for relevant studies that evaluated the relationship between ATB use and ICI efficacy using the PubMed, Embase, and conference databases. The primary outcomes consisted of overall survival (OS) and progression-free survival (PFS) measured by hazard ratios (HR) and corresponding 95% confidence intervals (CI). Subgroup and sensitivity analyses were also performed. A total of 19 eligible studies comprising 2,740 cancer patients treated with ICIs were included in the analysis. Our results indicated that ATB use was negatively associated with OS in cancer patients (HR = 2.37; 95% CI = 2.05-2.75; P < .001), without heterogeneity (I2 = 0.0%; P = .851). Moreover, ATB use significantly reduced PFS in patients treated with ICIs (HR = 1.84; 95% CI = 1.49-2.26; P < .001; I2 = 56.2%). Similar results were obtained in the subgroup analyses stratified by the time of ATB use and cancer type. Sensitivity analyses confirmed the stability of our results. Therefore, the findings of our meta-analysis indicated that ATB use is negatively associated with OS and PFS in cancer patients treated with ICI immunotherapy.

Circulating Noncoding RNAs Have a Promising Future Acting as Novel Biomarkers for Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide, causing a large number of cancer-related deaths each year. Patients are usually diagnosed at advanced and incurable stages due to the lack of suitable screening methods for early detection. Noncoding RNAs (ncRNAs), including small and long noncoding RNAs (lncRNA), are known to have significant regulatory functions, and accumulating evidence suggests that circulating ncRNAs have potential applications as noninvasive biomarkers for diagnosing CRC, evaluating its prognosis, or predicting chemosensitivity in the general population. In this review, we summarize the origins of circulating ncRNAs and provide details of single and multiple circulating ncRNAs that might have roles as diagnostic and prognostic biomarkers in CRC. We end by discussing circulating ncRNAs that may distinguish patients with resistance to chemotherapy.

Long non-coding RNA AB007962 is downregulated in gastric cancer and associated with poor prognosis.

A number of previous studies have reported that numerous long non-coding RNAs (lncRNAs) are dysregulated in gastric cancer (GC) and are involved in a series of biological and pathological processes. Total RNA was extracted from the cancerous tissues and matched normal adjacent tissues (NATs) of 96 patients with GC. The expression level of AB007962, a novel lncRNA, was determined by reverse transcription-quantitative polymerase chain reaction. The association between AB007962 expression levels and clinicopathological features were analyzed. Kaplan-Meier curves were also constructed in order to evaluate prognosis. Finally, publicly accessible data from The Cancer Genome Atlas was used to further verify the expression levels and clinical significance of AB007962. In conclusion, it was determined that the expression level of AB007962 was significantly reduced, compared with matched NATs in GC tissues (P=0.003). Survival analysis indicated that patients with intestinal-type GC with a reduced expression of AB007962 had a reduced prognosis, compared with those with an increased expression. AB007962 may be involved in the progression of GC and act as a novel prognostic biomarker for patients with GC, particularly in intestinal-type GC.

Impact of timing of adjuvant chemotherapy on survival in stage III colon cancer: a population-based study.

BACKGROUND: There is no consensus regarding the optimal time to initiate adjuvant chemotherapy after surgery for stage III colon cancer, and the relevant postoperative complications that cause delays in adjuvant chemotherapy are unknown. METHODS: Eligible patients aged ≥66 years who were diagnosed with stage III colon cancer from 1992 to 2008 were identified using the linked Surveillance, Epidemiology, and End Results-Medicare database. Kaplan-Meier analysis and a Cox proportional hazards model were utilized to evaluate the impact of the timing of adjuvant chemotherapy on overall survival (OS). RESULTS: A total of 18,491 patients were included. Delayed adjuvant chemotherapy was associated with worse OS (9-12 weeks: hazard ratio [HR] = 1.222, 95% confidence interval [CI] = 1.063-1.405; 13-16 weeks: HR = 1.252, 95% CI = 1.041-1.505; ≥ 17 weeks: HR = 1.969, 95% CI = 1.663-2.331). The efficacies of adjuvant chemotherapy within 5-8 weeks and ≤4 weeks were similar (HR = 1.045, 95% CI = 0.921-1.185). Compared with the non-chemotherapy group, chemotherapy initiated at ≥21 weeks did not significantly improve OS (HR = 0.882, 95% CI = 0.763-1.018). Patients with postoperative complications, particularly cardiac arrest, ostomy infection, shock, and septicemia, had a significantly higher risk of a 4- to 11-week delay in adjuvant chemotherapy (p < 0.05). CONCLUSIONS: Adjuvant chemotherapy initiated within 8 weeks was acceptable for patients with stage III colon cancer. Delayed adjuvant chemotherapy after 8 weeks was significantly associated with worse OS. However, adjuvant chemotherapy might still be useful even with a delay of approximately 5 months. Moreover, postoperative complications were significantly associated with delayed adjuvant chemotherapy.

High Platelet-to-Lymphocyte Ratio Predicts Poor Prognosis and Clinicopathological Characteristics in Patients with Breast Cancer: A Meta-Analysis.

BACKGROUND: We aimed to evaluate the correlation of platelet-to-lymphocyte ratio (PLR) with prognosis and clinicopathological characteristics of breast cancer. METHODS: The PubMed and Embase databases were searched. Hazard ratio (HR) with 95% confidence interval (CI) was used to summarize disease-free survival (DFS) and overall survival (OS). Odds ratio (OR) was used to summarize tumor clinicopathological characteristics. RESULTS: High PLR was associated with poor DFS and OS (DFS: HR = 1.47, 95% CI = 1.16-1.85, and Tau2 = 0.070; OS: HR = 1.88, 95% CI = 1.27-2.80, and Tau2 = 0.192). A Galbraith plot indicated that the studies by Allan et al. and Cihan et al. contributed the heterogeneity of DFS and OS, respectively. There were significant differences in the incidence of high PLR between stage II-IV and stage I groups (OR = 1.86, 95% CI = 1.20-2.90, and Tau2 < 0.001), between lymph node-positive and lymph node-negative groups (OR = 1.52, 95% CI = 1.22-1.91, and Tau2 =0.014), and between metastasis-positive and metastasis-negative groups (OR = 4.24, 95% CI = 2.73-6.59, and Tau2 < 0.001). CONCLUSIONS: Our results indicated that PLR was associated with poor prognosis of breast cancer and adequately predicted clinicopathological characteristics.

Non-coding RNAs participate in the regulatory network of CLDN4 via ceRNA mediated miRNA evasion.

Thousands of genes have been well demonstrated to play important roles in cancer progression. As genes do not function in isolation, they can be grouped into "networks" based on their interactions. In this study, we discover a network regulating Claudin-4 in gastric cancer. We observe that Claudin-4 is up-regulated in gastric cancer and is associated with poor prognosis. Claudin-4 reinforce proliferation, invasion, and EMT in AGS, HGC-27, and SGC-7901 cells, which could be reversed by miR-596 and miR-3620-3p. In addition, lncRNA-KRTAP5-AS1 and lncRNA-TUBB2A could act as competing endogenous RNAs to affect the function of Claudin-4. Our results suggest that non-coding RNAs play important roles in the regulatory network of Claudin-4. As such, non-coding RNAs should be considered as potential biomarkers and therapeutic targets against gastric cancer.Non-coding RNAs can modify the expression of proteins in cancer networks. Here the authors reveal a regulatory network in gastric cancer whereby claudin-4 expression is reduced by specific miRNAs, which are in turn bound by specific lncRNAs acting as competing endogenous RNAs (ceRNAs), resulting in increased claudin-4 expression.

Which is better for gastric cancer patients, perioperative or adjuvant chemotherapy: a meta-analysis.

BACKGROUND: The preferred chemotherapy method for gastric cancer continues to be matter of debate. We performed a meta-analysis to comparing prognosis and safety between perioperative chemotherapy and adjuvant chemotherapy to identify the better chemotherapy option for gastric cancer. METHODS: We searched the PubMed, EMBASE, Cochrane Library, and Ovid databases for eligible studies until February 2016. The main endpoints were prognostic value (hazard ratio [HR] for overall survival [OS] and 1-, 2-, 3-, and 5-year survival rate), response rate of chemotherapy, radical resection rate, post-operative complication rate, and adverse effects of chemotherapy. RESULTS: Five randomized controlled trials and six clinical controlled trials involving 1,240 patients were eligible for analysis. Compared with the adjuvant chemotherapy group, the perioperative chemotherapy group had significantly better prognosis (HR, 0.74; 95 % CI, 0.61 to 0.89; P < 0.01). The difference between the two groups remained significant in the studies that used combination chemotherapy as the neoadjuvant chemotherapy regimen (HR, 0.59; 95 % CI, 0.46 to 0.76; P < 0.01) but were not significant in the studies that used fluoropyrimidine monotherapy (HR, 0.93; 95 % CI, 0.56 to 1.55; P = 0.84). Furthermore, the two groups showed no significant differences in the post-operative complication rates (relative risk, 0.98; 95 % CI, 0.63 to 1.51; P = 0.91) or adverse effects of chemotherapy (P > 0.05 for all adverse effects). CONCLUSION: Perioperative chemotherapy showed improved survival compared to adjuvant chemotherapy for gastric cancer. In addition, combination chemotherapy resulted in better survival compared to monotherapy in the neoadjuvant chemotherapy regimens.

Impact of age on efficacy of postoperative oxaliplatin-based chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy.

BACKGROUND: Clinical practice guidelines focusing on age-related adjuvant chemotherapy for rectal cancer are currently limited. The present study aimed to explore the impact of age on the efficacy of adjuvant oxaliplatin-based chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy. METHODS: We performed a retrospective cohort analysis using data from the Surveillance, Epidemiology, and End Results-Medicare-linked database from 1992-2009. We enrolled patients with yp stages I-III rectal cancer who received neoadjuvant chemoradiotherapy and underwent curative resection. The age-related survival benefit of adding oxaliplatin to adjuvant 5-fluorouracil (5-FU) chemotherapy was evaluated using Kaplan-Meier survival analysis with propensity score-matching and Cox proportional hazards models. RESULTS: Comparing the oxaliplatin group with the 5-FU group, there were significant interactions between age and chemotherapy efficacy in terms of overall survival (OS) (p for interaction = 0.017) among patients with positive lymph nodes (ypN+). Adding oxaliplatin to 5-FU could prolong survival in patients aged < 73 years and ypN+ category, and but did not translate into survival benefits in patients aged ≥ 73 years and ypN+ category. No significant interactions were observed among ypN- patients, and oxaliplatin did not significantly improve OS, regardless of age. CONCLUSIONS: In patients with rectal cancer who have already received neoadjuvant chemoradiotherapy and undergone curative resection, adding oxaliplatin to 5-FU could prolong OS in patients aged < 73 years and ypN+ category. However, adding oxaliplatin did not translate into survival benefits in patients age ≥ 73 years and ypN+ category, or in ypN- patients.

Meta-analysis of the laparoscopic versus open colorectal surgery within fast track surgery.

BACKGROUND: Laparoscopic methods and fast-track surgery (FTS) can enhance recovery and reduce postoperative hospital stay. However, whether laparoscopic surgery can provide short-term benefits within FTS is controversial. Thus, we conducted a meta-analysis of published studies to evaluate the effect of laparoscopic colorectal surgery within FTS. METHODS: We searched PubMed, EMBASE, Cochrane Library, and Ovid databases for eligible studies. Endpoints were duration of postoperative hospital stay, time to first bowel movement, total postoperative complication rate, readmission rate, mortality within 30 days after surgery, and conversation rate of laparoscopic surgery. RESULTS: Four randomized controlled trials and six clinical controlled trials (1510 patients) were eligible for analyses. Duration of postoperative hospital stay (weighted mean difference, -1.65 days; p < 0.001), time to first bowel movement (-1.13 days; p < 0.001), total postoperative complication rate (risk ratio [RR], 0.65; p < 0.001), readmission rate (0.46; p < 0.001), and mortality (0.45; p < 0.001) were significantly reduced in the laparoscopic surgery group. Overall conversion rate of laparoscopic surgery was 11.1%. Subgroup analyses based on each FT element demonstrated that studies without the element "prevention of hypothermia," "no bowel preparation," or "no routine use of drains" did not show significant differences between two groups with regard to duration of postoperative hospital stay or total prevalence of postoperative complications. CONCLUSION: Within FTS, laparoscopic methods can significantly shorten postoperative hospital stay, accelerate postoperative recovery, and enhance safety in colorectal surgery. The FT elements "prevention of hypothermia," "no bowel preparation," and "no routine use of drains" may play important parts in the combined effect of these two methods.

A novel long noncoding RNA-LOWEG is low expressed in gastric cancer and acts as a tumor suppressor by inhibiting cell invasion.

PURPOSE: Long noncoding RNA (lncRNA) have been reported to be involved in the development of multiple cancers. The aim of this study was to report the identification of lncRNA-CTD-2108O9.1, which we have named lncRNA low expressed in gastric cancer (lncRNA-LOWEG), and investigate its role in cancer development. METHODS: Total RNA was extracted from the tissues of 94 patients with GC, one normal gastric epithelial cell line and four GC cell lines. Expression levels of lncRNA-LOWEG were determined by real-time PCR. Moreover, CCK-8 proliferation assay, transwell cell invasion assay and flow cytometry were performed to study the effects of lncRNA-LOWEG on SGC-7901 cell proliferation, cell invasion and cell cycle progression. Lastly, western blot and real-time PCR were used to verify the potential target genes of lncRNA-LOWEG. RESULTS: Significantly reduced expression of lncRNA-LOWEG was found in gastric cancer tissues and cell lines (SGC-7901, AGS, BGC-823 and HG-27) compared with patient-matched nontumorous adjacent tissues (P < 0.01) or the normal gastric cell line GES-1 (P < 0.05). Moreover, the transwell assay showed that the number of cells capable of passing through the Matrigel was significantly reduced after lncRNA-LOWEG transfection (P < 0.05). However, lncRNA-LOWEG overexpression did not significantly influence cell proliferation (P > 0.05) and cell cycle progression (P > 0.05). Lastly, western blot and real-time PCR analysis suggested that lncRNA-LOWEG is positively correlated with the expression of leukemia inhibitory factor receptor (LIFR) gene at the translational level. CONCLUSIONS: LncRNA-LOWEG is a tumor suppressor that inhibits GC cell invasion. And LIFR gene is up-regulated by lncRNA-LOWEG.

Clinicopathologic and Prognostic Value of Serum Carbohydrate Antigen 19-9 in Gastric Cancer: A Meta-Analysis.

BACKGROUND: The clinical value of carbohydrate antigen (CA) 19-9 in gastric cancer is controversial. We evaluated the clinicopathologic and prognostic value of CA 19-9 in gastric cancer. METHODS: A literature search was conducted in PubMed and Embase databases. Odds ratios (ORs), risk ratios (RR), hazard ratios (HRs), and 95% confidence intervals (CIs) were used as effect measures. RESULTS: Thirty-eight studies were included. Results showed that there were significant differences in the incidence of high CA 19-9 levels between stages III/IV and I/II groups (OR = 3.36; 95% CI = 2.34-4.84), the pT3/T4 and pT1/T2 groups (OR = 2.40; 95% CI = 1.60-3.59), the lymph node-positive and node-negative groups (OR = 2.91; 95% CI = 2.21-3.84), the metastasis-positive and metastasis-negative groups (OR = 2.76; 95% CI = 1.12-6.82), and vessel invasion-positive and invasion-negative groups (OR = 1.66; 95% CI = 1.11-2.48). Moreover, CA 19-9 was significantly associated with poor overall survival (HR = 1.83; 95% CI = 1.56-2.15), disease-free survival (HR = 1.85; 95% CI = 1.16-2.95), and disease-specific survival (HR = 1.33; 95% CI = 1.10-1.60) in gastric cancer. CONCLUSIONS: Our meta-analysis showed that CA 19-9 indicates clinicopathologic characteristics of gastric cancer and is associated with a poor prognosis.