Significance of dysregulated M2 macrophage and ESR2 in the ovarian metastasis of gastric cancer.

Background: Prognosis of gastric cancer (GC) patients with ovarian metastasis (OM) remains poor. We hereby characterized the role of tumor immune microenvironment (TIME) and identified potential key regulators in the OM with the aim of understanding its molecular basis to develop novel therapeutic targets. Methods: Transcriptomic analyses of paired primary and ovarian metastatic lesions of seven GC patients from Fudan University Shanghai Cancer Center uncovered and functionally annotated their differentially expressed genes (DEGs). CIBERSORT analysis revealed differential TIME between primary GCs and OMs, which was further validated by multiplex immunofluorescence (mIF). Unique overexpression of candidate regulator in OMs was validated by an immunohistochemical (IHC) staining-based cohort study and in vitro cell growth, migration and invasion assays were conducted to characterize its function in GC progression. Results: Functional enrichment analyses of DEGs between GCs and matched OMs revealed multiple significantly dysregulated immune-related and cancer-related pathways. Distinctive subsets of immune cells, especially M2 macrophage, were selectively enriched in metastatic lesions. mIF-based quantification further validated the overexpression of CD68+CD206+ M2 macrophage in the OMs. Estrogen receptor 2 (ESR2), which encodes estrogen receptor ß (ERß), was not only potentially correlated with M2 macrophage but also overexpressed in the OM of GC. ESR2 was up-regulated in cancerous tissue and its high expression correlated with younger age, more advanced lymph node metastasis and pathological stage, as well as a worse patient survival. IHC staining of ERß in the cohort of paired primary and metastatic GCs validated its selective overexpression in OMs. Small-interfering RNAs (siRNAs)-induced knockdown of ESR2 significantly inhibited the invasion and migration of both AGS and HGC-27 GC cell lines. Conclusions: Comparative RNA-sequencing analysis revealed the dysregulated TIME, M2 macrophage in particular, between primary GC and OM. ESR2 potentially correlated with M2 macrophage and played pro-oncogenic roles in GC progression and metastasis.

Clinical comparison of total gastrectomy with single-vessel transection Roux-en-Y(SR-Y) reconstruction versus total gastrectomy with conventional Roux-en-Y reconstruction for proximal gastric cancer.

PURPOSE: The aim of this study was to investigate the clinical benefits of single-vessel transection Roux-en-Y reconstruction following total gastrectomy. METHODS: A total of 194 patients with proximal gastric cancer were prospectively collected at Fudan University Shanghai Cancer Center between January 2021 and September 2022. This included 97 patients who underwent conventional Roux-en-Y reconstruction and 97 patients who underwent single-vessel transection Roux-en-Y reconstruction. Clinicopathological characteristics, surgical outcomes, and postoperative complications were compared between the conventional and single-vessel transection groups. RESULTS: There were no significant differences in baseline characteristics between the two groups in terms of age(p=0.882), sex (p=0.595), BMI(p=0.683), tumor location (p=0.568), TNM stage(p=0.122), tumor size(p=0.927), anemia (p=0.756), neoadjuvant chemotherapy(p=0.730) and surgical approach (p=0.592). However, in comparion with the conventional group, the single-vessel transection group had a shorter operation time (162.5±37.6min vs 178.5±48.3min; p=0.011) and less intraoperative bleeding (167.2±91.8ml vs 207.8±167.5ml; p=0.037) after complete reservation of the terminal jejunal vascular archs. Nevertheless, there were no significant differences in tensions of jejunal mesentery, durations of peritoneal drainage, postoperative hospital stay durations or the number of lymph node dissections and early complications between the two groups. CONCLUSIONS: The single-vessel transection Roux-en-Y reconstruction could simplify surgical procedures, reduce operating time, and minimize intraoperative bleeding without increasing tensions of jejunal mesentery or short-term complications. It is feasible and safe and worth further promotion in clinical practice.

Targeting SOX13 inhibits assembly of respiratory chain supercomplexes to overcome ferroptosis resistance in gastric cancer.

Therapeutic resistance represents a bottleneck to treatment in advanced gastric cancer (GC). Ferroptosis is an iron-dependent form of non-apoptotic cell death and is associated with anti-cancer therapeutic efficacy. Further investigations are required to clarify the underlying mechanisms. Ferroptosis-resistant GC cell lines are constructed. Dysregulated mRNAs between ferroptosis-resistant and parental cell lines are identified. The expression of SOX13/SCAF1 is manipulated in GC cell lines where relevant biological and molecular analyses are performed. Molecular docking and computational screening are performed to screen potential inhibitors of SOX13. We show that SOX13 boosts protein remodeling of electron transport chain (ETC) complexes by directly transactivating SCAF1. This leads to increased supercomplexes (SCs) assembly, mitochondrial respiration, mitochondrial energetics and chemo- and immune-resistance. Zanamivir, reverts the ferroptosis-resistant phenotype via directly targeting SOX13 and promoting TRIM25-mediated ubiquitination and degradation of SOX13. Here we show, SOX13/SCAF1 are important in ferroptosis-resistance, and targeting SOX13 with zanamivir has therapeutic potential.

Novel biogenic preparation of gold nanoparticles decorated on sepiolite clay and evaluation of anti-cancer effect on gastric cancer cell and electrochemical sensing of nitrite.

An environmentally friendly strategy was used in this study to synthesize gold nanoparticles decorated on sepiolite clay (GNPs-SC) using Heracleum persicum grass extract. The physicochemical characters of the prepared composite were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), and X-ray diffraction (XRD). A GNPs-SC modified carbon pate electrode (CPE) was used to study the electrochemical oxidation of nitrite. The proposed nitrite sensor exhibits excellent performance, including a broad linear range (1.0-150 µM), a low limit of detection (0.4 µM), and acceptable reproducibility (RSD = 2.6%). As well, the prepared GNPs-SC was tested for its effectiveness against human gastric adenocarcinoma (AGS) cell line. The MTT assay protocol revealed that the bio-synthesized product displayed significant cytotoxic activity against gastric cancer in human subjects. The findings of this study indicate that GNPs-SC, synthesized using environmentally friendly protocol, exhibit great potential for use in electrochemical sensing and treatment of human cancer.

Partial omentectomy maybe practicable for T3 or shallower gastric cancer patients.

BACKGROUND: Total omentectomy is often performed with gastrectomy as radical surgery for gastric cancer (GC) patients. However, it remains controversial whether GC patients can benefit from omentectomy. The aim of this study was to analyze the incidence and clinical significance of tumor deposits (TDs) in different anatomical subregions of perigastric omentum in GC patients undergoing gastrectomy with total omentectomy. METHODS: From October 2011 to December 2013, 1253 patients who underwent gastrectomy with total omentectomy for GC were retrospective reviewed. The TDs in different anatomical subregions of perigastric omentum were examined. RESULTS: Of 1253 patients, TDs positivity was 11.2%. Tumor deposits in the omentum of greater curvature and in the omentum of lesser curvature were associated with lymphovascular invasion, perineural invasion, advanced tumor node metastasis stages, and unfavorable survival. Besides, TDs in the proximal omentum of greater curvature and in the omentum of lesser curvature correlated with older patients and larger tumors. Kaplan-Meier curves showed that patients with TDs had worser overall survival (OS) than those without, regardless of TD positions. Patients with TDs in the omentum of greater curvature had the worst prognosis, followed by patients with TDs in the omentum of lesser curvature and patients with no TDs. Tumor deposits in the proximal omentum of greater curvature was an independent prognostic factor for OS. Moreover, only patients classified as pT4 had TDs in the distal omentum of greater curvature. CONCLUSIONS: Patients with TDs in the omentum of greater curvature had the worst prognosis, followed by patients with TDs in the omentum of lesser curvature and patients with no TDs. In addition, partial omentectomy might be practicable for gastric cancer patients classified as T3 or shallower tumors.

Tumor-infiltrating CD226+CD8+ T cells are associated with postoperative prognosis and adjuvant chemotherapeutic benefits in gastric cancer patients.

PURPOSE: Defining the phenotypic characteristics of CD8+ T cell subsets in gastric cancer (GC) can help remodel the immune microenvironment of the tumor, thereby improving patient prognosis. CD226 has recently been shown to regulate the activity of CD8+ T cell in several malignancies. However, the clinical relevance of CD226+CD8+ T cells in GC remains unclear. METHODS: Fudan University Shanghai Cancer Center (FUSCC) cohort (n = 316), The Cancer Genome Atlas (TCGA) cohort (n = 407), KUGH/KUCM cohort (n = 202), and Asian Cancer Research Group (ACRG) cohort (n = 300) were included in prognosis and response to adjuvant chemotherapy (ACT) analyses. Flow cytometry and multiplex immunostaining were used to characterize CD226+CD8+ T cells. RESULTS: CD226+CD8+ T cells predicted favorable outcomes in patients undergoing curative resection for GC. GC patients with high CD226+CD8+ T cell infiltration benefitted more from adjuvant chemotherapy. CD155 is upregulated in GC tissues and is associated with decreased intra-tumoral CD226+CD8+ T cell infiltration. The combination of intra-tumoral CD226+CD8+ T cells and CD155 is a strong prognostic predictor in patients with GC. CONCLUSION: CD226+CD8+ T cells may represent a novel therapeutic target and a useful marker of prognosis and therapeutic response in patients with GC.

Activation of MAT2A-ACSL3 pathway protects cells from ferroptosis in gastric cancer.

BACKGROUND: Ferroptosis, a unique form of nonapoptotic-regulated cell death caused by overwhelming lipid peroxidation, represents an emerging tumor suppression mechanism. Growing evidence has demonstrated that cell metabolism plays an important role in the regulation of ferroptosis. Specifically, the association between methionine metabolism and ferroptosis remains undefined. METHODS: We performed in vitro and in vivo experiments to evaluate the influence of methionine metabolism on ferroptosis sensitivity. Pharmacological and genetic blockade of the methionine cycle was utilized and relevant molecular analyses were performed. RESULTS: We identified MAT2A as a driver of ferroptosis resistance. Mechanistically, MAT2A mediates the production of S-adenosylmethionine (SAM), which upregulates ACSL3 by increasing the trimethylation of lysine-4 on histone H3 (H3K4me3) at the promoter area, resulting in ferroptosis resistance. CONCLUSIONS: Collectively, these results established a link between methionine cycle activity and ferroptosis vulnerability in gastric cancer.

LncRNA SLCO4A1-AS1 Accelerates Growth and Metastasis of Gastric Cancer via Regulation of the miR-149/XIAP Axis.

OBJECTIVE: Recently, long noncoding RNA SLCO4A1 antisense RNA 1 (SLCO4A1-AS1) has been shown to act as an oncogene in several cancer types; however, its role in gastric cancer (GC) and its underlying molecular mechanisms are yet to be elucidated. METHODS: Using the ENCORI database, we identified SLCO4A1-AS1, miR-149-5p (miR-149), and the X-linked inhibitor of apoptosis (XIAP) whose expressions were obviously changed in GC samples, and analyzed the correlation between their expressions in GC samples. Moreover, we explored the expression of SLCO4A1-AS1, miR-149, and XIAP in clinical samples and GC cell lines using RT-qPCR and western blotting assay; the correlation between them was analyzed using RNA immunoprecipitation and dual-luciferase reporter. CCK-8, colony formation, and Transwell assays were conducted to determine the effects of SLCO4A1-AS1, miR-149, and XIAP expression on cell proliferation, migration, and invasion, respectively. A nude mouse xenograft model was used to explore their function in xenograft growth. RESULTS: SLCO4A1-AS1 was significantly upregulated in the GC samples and cell lines, and a high level of SLCO4A1-AS1 was associated with an advanced tumor stage and shortened patient survival. Mechanistically, SLCO4A1-AS1 post-transcriptionally regulated XIAP by functioning as competing endogenous RNA in GC to sponge miR-149. Further functional assays revealed that the overexpression of miR-149 and knockdown of XIAP considerably inhibited GC cell viability and its migratory and invasive characteristics in vitro. SLCO4A1-AS1 knockdown also determined the function of GC cells but was diminished by the miR-149 inhibitor in vitro. Finally, we demonstrated that the deletion of SLCO4A1-AS1 suppressed tumor growth and metastasis in vivo. CONCLUSIONS: Altogether, these findings suggest that SLCO4A1-AS1 functions as a crucial oncogenic lncRNA in GC and it can facilitate GC tumor growth and metastasis by interacting with miR-149 and enhancing XIAP expression. Therefore, SLCO4A1-AS1 is a potential novel therapeutic target in GC treatment.

Crocetin suppresses angiogenesis and metastasis through inhibiting sonic hedgehog signaling pathway in gastric cancer.

Gastric cancer (GC) is one of the major causes of cancer-related deaths and chemoresistance is a key obstacle to the treatment of GC, particularly in advanced GC. As an active component of saffron stigma, crocetin has important therapeutic effects on various diseases including tumors. However, the therapeutic potential of crocetin targeting GC is still unclear and the underlying mechanisms are remained to be further explored. In this study, crocetin significantly inhibited angiogenesis in GC, including tubes of HUVECs and vasculogenic mimicry (VM) formation of GC cells. Crocetin also suppressed cell proliferation, migration and invasion. To explore which signaling pathway involving in crocetin, HIF-1α, Notch1, Sonic hedgehog (SHH) and VEGF were examined with crocetin treatment and we found that SHH significantly decreased. Crocetin suppressed SHH signaling with SHH, PTCH2, Sufu and Gli1 protein level decreased in western blot assay. In addition, crocetin suppressed SHH secretion in GC and HUVEC cells. The promoted effects on cell migration induced by secreted SHH were also inhibited by crocetin in GC and HUVEC cell co-culture system. Furthermore, recombinant SHH promoted angiogenesis as well as cell migration and proliferation. However, these promoted effects were reversed by crocetin treatment. These results revealed that crocetin suppressed GC angiogenesis and metastasis through SHH signaling pathway, indicating that crocetin may function as an effective therapeutic drug against GC.

Apatinib combined with PD-L1 blockade synergistically enhances antitumor immune responses and promotes HEV formation in gastric cancer.

PURPOSE: Apatinib, an antiangiogenic drug, has shown beneficial effects only in a fraction of advanced gastric cancer (GC) patients. Given the recent success of immunotherapies, combination of apatinib with immune checkpoint inhibitor may provide sustained and potent antitumor responses. METHODS: Immunocompetent mice with subcutaneous MFC tumors grown were given a combination of apatinib and anti-PD-L1 antibody therapy. GC tissues from patients undergoing curative resection in China were collected, and the density of HEVs, MSI status and tumor-infiltrated lymphocytes were analyzed by immunohistochemical staining. RESULTS: Combined apatinib and PD-L1 blockade therapy synergistically delayed tumor growth and increased survival in MFC-bearing immunocompetent mice. The combination therapy promoted antitumor immunity by increasing the ratio of CD8+ cytotoxic T cells to Foxp3+ Treg cells, the accumulation of CD20+ B cells and the Th1/Th2 cytokine ratio (IFN-γ/IL-10). The combination therapy induced the formation of HEVs through activation of LTßR signaling, thus promoting CD8+ cytotoxic T cell and CD20+ B cell infiltration in tumors. In clinical GC samples, the density of HEVs positively correlated with the intratumoral infiltration of CD8+ cytotoxic T cells and CD20+ B cells. MSI-high GC showed a higher density of HEVs, CD8+ cytotoxic T cells and CD20+ B cells than MSS/MSI-low GC. GC patients with high densities of HEVs, CD8+ cytotoxic T cells and CD20+ B cells had an improved prognosis with superior overall survival. CONCLUSION: Combining apatinib with PD-L1 blockade treatment synergistically enhances antitumor immune responses and promotes HEV formation in GC.

MiRNA-339-5p suppresses the malignant development of gastric cancer via targeting ALKBH1.

OBJECTIVE: To uncover the role of microRNA-339-5p (miRNA-339-5p) in the development of gastric cancer (GC) and its possible molecular mechanism. METHODS: Differential expressions of miRNA-339-5p in GC and adjacent normal tissues were detected. The relationship between miRNA-339-5p level and clinical features in GC patients was analyzed. Proliferative and migratory changes in BGC-823 and SGC-7901 cells overexpressing miRNA-339-5p were examined. Finally, luciferase assay and rescue experiments were conducted to explore the regulatory mechanism of miRNA-339-5p in its downstream gene ALKBH1, and their interaction in the development of GC. RESULTS: MiRNA-339-5p was downregulated in GC tissues. Lowly expressed miRNA-339-5p was unfavorable to prognosis in GC because of high rates of lymphatic metastasis and distant metastasis. Overexpression of miRNA-339-5p markedly reduced proliferative and migratory abilities in GC cells. ALKBH1 was identified to be the downstream gene of miRNA-339-5p. In GC tissues, ALKBH1 was upregulated and negatively correlated to miRNA-339-5p level. Overexpression of ALKBH1 was able to reverse the inhibitory effects of overexpressed miRNA-339-5p on proliferative and migratory abilities in GC. CONCLUSIONS: Lowly expressed miRNA-339-5p is closely related to metastasis and poor prognosis in GC patients. MiRNA-339-5p suppresses the malignant development of GC by negatively regulating ALKBH1.

NUCKS1 promotes gastric cancer cell aggressiveness by upregulating IGF-1R and subsequently activating the PI3K/Akt/mTOR signaling pathway.

The effects of nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) on tumor cells and the relevant mechanisms are less well defined. This study aimed to explore the role and mechanism of action of NUCKS1 in gastric cancer (GC) progression. The expression dynamics of NUCKS1 were examined using microarray-based immunohistochemistry (IHC) in a group of carcinomatous and adjacent non-tumor specimens. Various in vitro and in vivo assays were performed to clarify the function of NUCKS1 in GC and its underlying mechanisms. In our research, NUCKS1 overexpression was identified by IHC in 86/200 (43%) GC patients, was significantly related to the invasive phenotype of GC and was an indisputable predictor of shortened survival. Depleting NUCKS1 in GC cells significantly induced apoptosis and reduced cell proliferation and invasiveness in vitro and inhibited tumor growth in vivo. Additionally, ectopic overexpression of NUCKS1 in GC cells enhanced proliferation and invasion in vitro and promoted tumor growth in vivo. Importantly, PI3K/Akt/mTOR signaling pathway activity was inhibited upon downregulation of NUCKS1 expression and enhanced by ectopic overexpression of NUCKS1. Subsequently, the insulin-like growth factor 1 receptor (IGF-1R) gene was found to be a potential downstream target of NUCKS1 in GC cells, and knockdown of IGF-1R eliminated the augmentation of GC cell migration, invasion and proliferation as well as PI3K/Akt/mTOR signaling pathway activity by ectopic NUCKS1. The data suggested that NUCKS1 enhanced GC aggressiveness via the PI3K/Akt/mTOR signaling pathway in an IGF-1R-dependent manner. NUCKS1 or its respective signaling pathways could hold immense promise as potent anticancer targets for GC treatment.

Body mass index, serum total cholesterol, and risk of gastric high-grade dysplasia: A case-control study among Chinese adults.

Obesity is related to an increased risk of gastric cardia cancer. However, the influences of excess body weight and serum total cholesterol on the risk of gastric high-grade dysplasia have not been fully characterized.A case-control study was conducted to explore the relationships between body mass index (BMI), serum total cholesterol level, and the risk of gastric high-grade dysplasia in Chinese adults. A total of 893 consecutive patients with gastric high-grade dysplasia (537 men and 356 women) and 902 controls (543 men and 359 women) were enrolled from January 2000 to October 2015. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated, and a multivariate analysis was conducted.After adjusting for age, alcohol consumption, smoking status, family history of gastric cancer or esophageal cancer, and serum total cholesterol level, a BMI ranging from 27.5 to 29.9 was significantly related to an increased risk of gastric high-grade dysplasia in both men (adjusted OR = 1.87, 95% CI = 1.24-2.81) and women (adjusted OR = 2.72, 95% CI = 1.44-5.16). The 2 highest BMI categories (27.5-29.9 and ≥30.0) were identified as risk factors for gastric cardia high-grade dysplasia in both men (BMI = 27.5-29.9: adjusted OR = 1.78, 95% CI = 1.02-3.10; BMI ≥ 30.0: adjusted OR = 2.54, 95% CI = 1.27-5.08) and women (BMI = 27.5-29.9: adjusted OR = 2.88, 95% CI = 1.27-6.55; BMI ≥ 30.0: adjusted OR = 2.77, 95% CI = 1.36-5.64), whereas only a BMI ranging from 27.5 to 29.9 was a risk factor for gastric noncardia high-grade dysplasia in both men (adjusted OR = 1.98, 95% CI = 1.25-3.14) and women (adjusted OR = 2.88, 95% CI = 1.43-5.81). In addition, higher serum total cholesterol was associated with an increased risk of gastric noncardia high-grade dysplasia (adjusted OR = 1.83, 95% CI = 1.25-2.69) in women.Increased BMI was associated with an increased risk of gastric high-grade dysplasia in both men and women, and higher serum total cholesterol increased the risk of gastric noncardia high-grade dysplasia in women.

Significance of Serum Pepsinogens as a Biomarker for Gastric Cancer and Atrophic Gastritis Screening: A Systematic Review and Meta-Analysis.

BACKGROUND: Human pepsinogens are considered promising serological biomarkers for the screening of atrophic gastritis (AG) and gastric cancer (GC). However, there has been controversy in the literature with respect to the validity of serum pepsinogen (SPG) for the detection of GC and AG. Consequently, we conducted a systematic review and meta-analysis to assess the diagnostic accuracy of SPG in GC and AG detection. METHODS: We searched PubMed, Embase, and the Chinese National Knowledge Infrastructure (CNKI) for correlative original studies published up to September 30, 2014. The summary sensitivity, specificity, positive diagnostic likelihood ratio (DLR+), negative diagnostic likelihood ratio (DLR-), area under the summary receiver operating characteristic curve (AUC) and diagnostic odds ratio (DOR) were used to evaluate SPG in GC and AG screening based on bivariate random effects models. The inter-study heterogeneity was evaluated by the I2 statistics and publication bias was assessed using Begg and Mazumdar's test. Meta-regression and subgroup analyses were performed to explore study heterogeneity. RESULTS: In total, 31 studies involving 1,520 GC patients and 2,265 AG patients were included in the meta-analysis. The summary sensitivity, specificity, DLR+, DLR-, AUC and DOR for GC screening using SPG were 0.69 (95% CI: 0.60-0.76), 0.73 (95% CI: 0.62-0.82), 2.57 (95% CI: 1.82-3.62), and 0.43 (95% CI: 0.34-0.54), 0.76 (95% CI: 0.72-0.80) and 6.01 (95% CI: 3.69-9.79), respectively. For AG screening, the summary sensitivity, specificity, DLR+, DLR-, AUC and DOR were 0.69 (95% CI: 0.55-0.80), 0.88 (95% CI: 0.77-0.94), 5.80 (95% CI: 3.06-10.99), and 0.35 (95% CI: 0.24-0.51), 0.85 (95% CI: 0.82-0.88) and 16.50 (95% CI: 8.18-33.28), respectively. In subgroup analysis, the use of combination of concentration of PGI and the ratio of PGI:PGII as measurement of SPG for GC screening yielded sensitivity of 0.70 (95% CI: 0.66-0.75), specificity of 0.79 (95% CI: 0.79-0.80), DOR of 6.92 (95% CI: 4.36-11.00), and AUC of 0.78 (95% CI: 0.72-0.81), while the use of concentration of PGI yielded sensitivity of 0.55 (95% CI: 0.51-0.60), specificity of 0.79 (95% CI: 0.76-0.82), DOR of 6.88 (95% CI: 2.30-20.60), and AUC of 0.77 (95% CI: 0.73-0.92). For AG screening, the use of ratio of PGI:PGII as measurement of SPG yielded sensitivity of 0.69 (95% CI: 0.52-0.83), specificity of 0.84 (95% CI: 0.68-0.93), DOR of 11.51 (95% CI: 6.14-21.56), and AUC of 0.83 (95% CI: 0.80-0.86), the use of combination of concentration of PGI and the ratio of PGI:PGII yield sensitivity of 0.79 (95% CI: 0.72-0.85), specificity of 0.89 (95% CI: 0.85-0.93), DOR of 24.64 (95% CI: 6.95-87.37), and AUC of 0.87 (95% CI: 0.81-0.92), concurrently, the use of concentration of PGI yield sensitivity of 0.46 (95% CI: 0.38-0.54), specificity of 0.93 (95% CI: 0.91-0.95), DOR of 19.86 (95% CI: 0.86-456.91), and AUC of 0.86 (95% CI: 0.52-1.00). CONCLUSION: SPG has great potential as a noninvasive, population-based screening tool in GC and AG screening. In addition, given the potential publication bias and high heterogeneity of the included studies, further high quality studies are required in the future.

Circulating microRNAs and long non-coding RNAs in gastric cancer diagnosis: An update and review.

Gastric cancer (GC) is the fourth most common cancer and the third leading cause of cancer mortality worldwide. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are the most popular non-coding RNAs in cancer research. To date, the roles of miRNAs and lncRNAs have been extensively studied in GC, suggesting that miRNAs and lncRNAs represent a vital component of tumor biology. Furthermore, circulating miRNAs and lncRNAs are found to be dysregulated in patients with GC compared with healthy individuals. Circulating miRNAs and lncRNAs may function as promising biomarkers to improve the early detection of GC. Multiple possibilities for miRNA secretion have been elucidated, including active secretion by microvesicles, exosomes, apoptotic bodies, high-density lipoproteins and protein complexes as well as passive leakage from cells. However, the mechanism underlying lncRNA secretion and the functions of circulating miRNAs and lncRNAs have not been fully illuminated. Concurrently, to standardize results of global investigations of circulating miRNAs and lncRNAs biomarker studies, several recommendations for pre-analytic considerations are put forward. In this review, we summarize the known circulating miRNAs and lncRNAs for GC diagnosis. The possible mechanism of miRNA and lncRNA secretion as well as methodologies for identification of circulating miRNAs and lncRNAs are also discussed. The topics covered here highlight new insights into GC diagnosis and screening.

Effect of Neoadjuvant Chemotherapy Treatment on Prognosis of Patients with Advanced Gastric Cancer: a Retrospective Study.

OBJECTIVE: To evaluate the prognostic effects of neoadjuvant chemotherapy (NAC) in patients with local advanced gastric cancer. METHODS: We retrospectively analyzed prognosis in 191 patients with advanced gastric cancer, of whom 71 were treated with NAC and 120 received surgery only between February 2007 and July 2013. Postoperative complication rate was recorded. Survival by clinicopathological features, pathological T and N stages, and histopathological tumor regression was retrospectively compared between the two groups. RESULTS: According to Response Evaluation Criteria in Solid Tumors, none of the 71 patients in the NAC followed by surgery group showed complete response, 36 showed partial response, 25 had stable disease, and 10 had progressive disease. The chemotherapy response rate was 50.7%; the disease control rate was 85.9%. Grade 3/4 adverse events were seen in less than 20% patients, with acceptable toxicities. No difference was found in the overall postoperative complication rates between the two groups (7 versus 22 cases, P=0.18). Median survival time was significantly different, at 54 months in the NAC combined with surgery group and 25 months in the surgery-only group (P=0.025). CONCLUSION: In patients with operable gastric adenocarcinomas, NAC can significantly improve overall survival without increasing surgical complications.

Annexin A2 and CD105 expression in pancreatic ductal adenocarcinoma is associated with tumor recurrence and prognosis.

To investigate the value of expression of annexin A2, microvessel density (MVD) and CD105 in pancreatic ductal adenocarcinoma (PDAC) tissues and adjacent normal tissues, immunohistochemical staining was used. The positive expression rate of Annexin A2 and the MVD in pancreatic ductal adenocarcinoma tissues was higher than that in in adjacent normal tissues (p<0.005). Expression of Annexin A2 and MVD correlated with histological grade (p<0.05). MVD of cancers in TNM stage IIb was higher than that in TNM stageI~IIa (p<0.026). Cancerous tissues with Annexin A2 staining grade 3+ had lower MVD than the tissues with the other Annexin A2 staining grade (p<0.05). Patients with high MVD had worse prognosis. However , our study did not confirm Annexin A2 was an independent risk factor for patients with PDAC. We confirmed MVD labeled by CD105 was an independent risk factor for patients with PDAC and had moderate predictive value of prognosis.