Palladium and Iron Cocatalyzed Aerobic Alkene Aminoboration.

Aminoboration of simple alkenes with nitrogen nucleophiles remains an unsolved problem in synthetic chemistry; this transformation can be catalyzed by palladium via aminopalladation followed by transmetalation with a diboron reagent. However, this catalytic process faces inherent challenges with instability of the alkylpalladium(II) intermediate toward ß-hydride elimination. Herein, we report a palladium/iron cocatalyzed aminoboration, which enables this transformation. We demonstrate these conditions on a variety of alkenes and norbornenes with an array of common nitrogen nucleophiles. In the developed strategy, the iron cocatalyst is crucial to achieving the desired reactivity by serving as a halophilic Lewis acid to release the transmetalation-active cationic alkylpalladium intermediate. Furthermore, it serves as a redox shuttle in the regeneration of the Pd(II) catalyst by reactivation of nanoparticulate palladium.

Pd-Catalyzed Enantioselective [6+4] Cycloaddition of Vinyl Oxetanes with Azadienes to Access Ten-Membered Heterocycles.

We report herein the first enantioselective cycloaddition of vinyl oxetanes, the reaction of which with azadienes provided unprecedented access to ten-membered heterocycles through a [6+4] cycloaddition. By using a commercially available chiral Pd-SIPHOX catalyst, a wide range of benzofuran- as well as indole-fused heterocycles could be accessed in excellent yield and enantioselectivity. A unique Lewis acid induced fragmentation of these ten-membered heterocycles was also discovered.

Palladium-Titanium Relay Catalysis Enables Switch from Alkoxide-π-Allyl to Dienolate Reactivity for Spiro-Heterocycle Synthesis.

Reported herein is the divergent syntheses of [5,5] and [6,5] spiro-heterocycles under Lewis-acid-assisted palladium catalysis. In particular, an unprecedented switch from alkoxide-π-allyl to dienolate reactivity was achieved by the use of palladium-titanium relay catalysis, and represents umpolung reactivity of vinylethylene carbonates. This method uses a simple procedure and commercially available catalysts, and delivers both classes of spiro-heterocycles, bearing three contiguous stereocenters, in high yield and uniformly excellent diastereoselectivity.

Nine-Membered Benzofuran-Fused Heterocycles: Enantioselective Synthesis by Pd-Catalysis and Rearrangement via Transannular Bond Formation.

The first enantioselective formal [5+4] cycloaddition is realized under palladium catalysis to deliver benzofuran-fused nine-membered rings. These medium-sized heterocycles and derivatives undergo unique rearrangements induced by transannular bond formation, resulting in the production of two classes of densely substituted polycyclic heterocycles in excellent efficiency and stereoselectivity.

Construction of Nine-Membered Heterocycles through Palladium-Catalyzed Formal [5+4] Cycloaddition.

The first catalytic formal [5+4] cycloaddition to prepare nine-membered heterocycles is presented. Under palladium catalysis, the reaction of N-tosyl azadienes and substituted vinylethylene carbonates (VECs) proceeds smoothly to produce benzofuran-fused heterocycles in uniformly high efficiency. Highly diastereoselective functionalization of the nine-membered heterocycles through peripheral attack is also demonstrated.

Genetic variations in the mTOR gene contribute toward gastric adenocarcinoma susceptibility in an Eastern Chinese population.

BACKGROUND AND AIM: Genetic variants in the mammalian target of rapamycin (mTOR) gene have become an interesting topic for the study of genetic susceptibility to cancer, but their associations with the risk of gastric cancer have not been fully investigated. MATERIALS AND METHODS: In a hospital-based case-control study of 1002 gastric cancer patients and 1003 cancer-free controls, we genotyped four potentially functional single nucleotide polymorphisms (SNPs) (rs1034528G>C, rs17036508T>C, rs3806317A>G, and rs2295080T>G) of mTOR and assessed their associations with the risk of gastric cancer using univariate and multivariate logistic regression analyses. We also used the multifactorial dimension reduction analysis to explore possible interactions and the false-positive report probabilities to assess significant findings. RESULTS: We found that rs1034528 CG/CC and rs3806317 GA/GG variant genotypes were associated with an increased risk of gastric cancer under a dominant model (adjusted odds ratio=1.27 and 1.22, respectively). In the combined analysis of all four SNPs under investigation, patients with 3-4 risk genotypes of mTOR had a significantly increased risk of gastric cancer (adjusted odds ratio=1.46, 95% confidence interval=1.19-1.79) compared with those with 0-2 risk genotypes. Stratified analysis indicated that this risk was more pronounced in subgroups of men, never-smokers, never-drinkers, and clinical stages III+IV. The multifactorial dimension reduction analysis suggested some evidence of interactions between the combined genotypes and other risk factors for gastric cancer. CONCLUSION: These findings suggest that potentially functional SNPs of mTOR may individually or collectively contribute to the risk of gastric cancer. Larger studies with diverse ethnic populations are warranted to validate our findings.

Matrix metalloproteinase-7 mRNA and protein expression in gastric carcinoma: a meta-analysis.

Messenger RNA (mRNA) acts as template for protein synthesis. The matrix metalloproteinase-7 (MMP-7) protein and its mRNA expression have been suggested to be involved in the development of various diseases and cancers. We aimed to study associations between the MMP-7 protein and mRNA expression in gastric carcinoma (GC) patients. We searched in the Science Citation Index, the Cochrane Library, PubMed, Embase, CINAHL, Current Contents Index, and several Chinese databases. Studies were pooled and odds ratios and their corresponding 95 % confidence intervals were calculated. Subgroup analyses and publication bias detection were also conducted. Statistical analysis was performed via Version 12.0 STATA software. An updated meta-analysis based on 16 independent cohort studies was performed to investigate this association. The study suggests that significant differences in MMP-7 protein levels were observed in tumor-node-metastasis (TNM) I-II vs. III-IV (odds radio (OR) =3.19, 95 % confidence interval (95%CI) =1.59 ∼ 6.41, P=0.001), in T1-2 vs. T3-4 invasive grade (OR=1.82, 95%CI=1.07 ∼ 3.12, P=0.028), and in distant metastasis-positive vs. metastasis-negative samples (OR=3.14, 95%CI=1.05 ∼ 9.35, P=0.040). Increased MMP-7 mRNA levels were found to be significantly correlated with invasive grade (T3-4 vs. T1-2: OR=5.61, 95%CI=2.64 ∼ 11.95, P<0.001) and in the lymph node (LN) metastasis (positive vs. negative: OR=7.08, 95%CI=4.20 ∼ 11.93, P<0.001) group. Country subgroup analysis yielded significantly different estimates in the protein expression of MMP-7 of all experimental groups. MMP-7 mRNA levels were increased in LN metastasis-positive GC in contrast to metastasis-negative in China and Korea (all P<0.05); this was not shown in Japan (P>0.05). Higher protein and mRNA levels of MMP-7 were statistically associated with aggressive LN metastasis, advanced TNM stage, and invasion in GC patients; MMP-7 can thus potentially serve as a useful biomarker in determining GC progression and prognosis.

Genetic variations of mTORC1 genes and risk of gastric cancer in an Eastern Chinese population.

Mammalian target of rapamycin complex 1 (mTORC1) plays an important role in maintaining proper cellular functions, and genetic variations in this complex may affect cancer risk. In this study, we examined the associations between eight potential functional single nucleotide polymorphisms in the mTORC1 genes (rs2536T>C and rs1883965G>A for mTOR, rs3160T>C, and rs26865A>G for mLST8, rs3751934C>A, rs1062935T>C, rs3751932T>C, and rs12602885G>A for Raptor, not included in published gastric cancer genome-wide association studies) and gastric cancer risk in 1125 gastric cancer cases and 1196 cancer-free controls. We performed conditional logistic regression and multifactor dimensionality reduction (MDR) analyses to assess their associations with gastric cancer risk. We also used false-positive report probabilities (FPRP) for assessing significant findings. We found that only the rs1883965A variant genotypes were associated with an increased risk of gastric cancer (AG vs. GG: adjusted odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.00-1.59; AA vs. GG: adjusted OR = 1.85, 95% CI = 0.67-5.16 and dominant model: adjusted OR = 1.28, 95% CI = 1.03-1.61). Patients with ≥1 risk genotypes of mTOR had significant increased risk (adjusted OR = 1.25, 95% CI = 1.04-1.49), compared with those having zero risk genotypes. In the stratified analysis, the risk effect of the rs1883965 AG/AA genotypes was evident in subgroups of ever-smokers, non-gastric cardia adenocarcinoma and clinical stage I + II, which were noteworthy findings as evaluated by FPRP. The MDR analysis identified smoking status and rs1883965 as the strongest two-factors for gastric cancer risk. These data support the hypothesis that functional polymorphisms of mTOR may contribute to gastric cancer risk. Clearly, our results require validation in larger studies with different ethnic populations.

Polymorphisms in the XPG gene and risk of gastric cancer in Chinese populations.

DNA repair genes play an important role in maintaining stability and integrity of genomic DNA. Polymorphisms in nucleotide excision repair genes may cause variations in DNA repair capacity phenotype and thus contribute to cancer risk. In this case-control study of 1,125 gastric cancer cases and 1,196 cancer-free controls, we investigated the association between three functional single nucleotide polymorphisms (SNPs, rs2296147T > C, rs2094258C > T and rs873601G > A) in the xeroderma pigmentosum group G (XPG) gene and gastric cancer risk. We used the Taqman assays to genotype these three SNPs and logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that only the rs873601A variant genotypes were associated with a significant higher risk for gastric adenocarcinoma (adjusted OR = 1.30, 95% CI = 1.03-1.64 for AA vs. GG and adjusted OR = 1.23, 95% CI = 1.01-1.49 for AA vs. GG/AG). Stratification analysis indicated that this risk was more pronounced in subgroups of older age (>59 years), males, ever-smokers, and patients with NGCA. All these were not found for the other two SNPs (rs2296147T > C and rs2094258C > T). We then performed expression analysis using gastric cancer adjacent normal tissues from 141 patients and found that the A variant allele was associated with non-significantly reduced expression of XPG mRNA (P(trend) = 0.107). Further analysis using mRNA expression data from the HapMap suggested that the A allele was associated with significantly reduced expression of XPG mRNA in normal cell lines for 45 Chinese (P(trend) = 0.003) as well as for 261 subjects with different ethnicities (P(trend) = 0.001). These support the hypothesis that functional XPG variants may contribute to the risk of gastric cancer. Larger studies with different ethnic populations are warranted to validate our findings.

Are biomarkers correlated with recurrence patterns in patients with resectable gastric adenocarcinoma.

The aims of this study are to analyze the failure patterns in radical resected gastric adenocarcinoma, and to evaluate the correlation between recurrence patterns and potentially prognostic factors, including clinical pathological characteristic and biomarkers. Between Jan 2004 and Jun 2006, 84 patients were enrolled into the database analysis, including 8 with clinical stage I, 20 with clinical stage II, 21 with clinical stage IIIA, 22 with clinical stage IIIB and 13 with clinical stage IV, male 61 and female 23. The collected biomarkers including: preoperative tumor markers: CEA, AFP, CA199, CA50, CA72-4 and CA24-2; postoperative immunohistochemical (IHC) markers: Bax, Bcl-2, P27, CyclinD1, TOPO2, MDR, GST-π, Ki67, epidermal growth factor receptor (EGFR), P21, P53, proliferating cell nuclear antigen (PCNA), C-myc and Neu. Three-year local control rate (LCR), disease-free survival (DFS) and over-all survival (OS) were 66, 61 and 64% respectively. Logistic regression analysis showed cyclinD1 and CEA were correlated with prognosis; cyclinD1, CEA were correlated with loco-regional recurrence; PCNA was correlated with remote metastasis; bcl-2, ki67, c-myc2 and Neu were correlated with lymph node metastasis. The present study indicate that patterns of recurrence are variable and may be associated with specific biomarkers, in addition, high level of CEA and low-expressed of cyclinD1 resulted in poor prognosis.

Palladium-Catalyzed Oxidative Amination of α-Olefins with Indoles.

Herein we report the use of indoles, one of the most common nitrogen-containing heterocycles in FDA-approved drugs, as nucleophiles in the Pd-catalyzed aza-Wacker reaction. This N-functionalization of indoles is a Markovnikov selective olefin functionalization of simple alkenes using catalytic Pd(NPhth)2(PhCN)2 and O2 as the terminal oxidant in the presence of catalytic Bu4NBr. Various substituted indoles and alkenes are found to participate; 21 examples are presented with yields ranging from 41 to 97% isolated yield. Additionally, lactams and oxazolidinones are shown to participate under the reaction conditions. Mechanistic investigations suggest that the phthalimide ligand and Bu4NBr additive slow undesired side reactions: indole decomposition and olefin isomerization, respectively.

Preparation of mononuclear, homodinuclear, and heterotrinuclear complexes by salicylaldiminato-functionalized imidazolium salt: approach to multifunctional catalysts.

A salicylaldiminato imidazolium salt that bears both a Schiff base and imidazolium salt moiety was used to synthesize heterometallic compounds that could serve as multifunctional catalysts in certain reactions. The successful preparation of seven mononuclear compounds with a variety of transition metals (Pd, Ir, Ru, Zn, Ni) illustrated the high versatility of this class of ligands, which is crucial for the design of catalysts. Synthesis of homodinuclear compounds and heterotrinuclear compounds provided practical methods to connect multiple metal fragments through these ligands. The heterotrinuclear complex (Ni/Ir) was employed as a catalyst in the reaction of dehalogenation/transfer hydrogenation of halo-acetophenones. The preliminary catalytic study showed that this heterometallic species is more active than a combination of the corresponding monometallic species.

Copper-Catalyzed Three-Component Alkene Carbofunctionalization: C-N, C-O, and C-C Bond Formation from a Single Reaction Platform.

A general system achieving three-component intermolecular carbofunctionalization of alkenes is presented, including carboetherification, carboesterification, carboarylation, and carboamination. The scope of the reaction is presented with respect to the carbon electrophile, the olefin, and the nucleophile. Furthermore, the synthesis of γ-lactams via a carboamination reaction is demonstrated in a telescoped three-step protocol.

Stereoselective access to [5.5.0] and [4.4.1] bicyclic compounds through Pd-catalysed divergent higher-order cycloadditions.

Medium-sized rings, including those embedded in bridged and fused bicyclic scaffolds, are common core structures of myriad bioactive molecules. Among various synthetic strategies towards their synthesis, intermolecular higher-order cycloaddition provides great potential to build complex medium-sized rings from simple building blocks. Unfortunately, such transformations are often plagued with competitive reaction pathways and low levels of site- and stereoselectivity. Herein, we report catalyst-controlled divergent access to three classes of medium-sized bicyclic compounds in high efficiency and stereoselectivity, by palladium-catalysed cycloadditions of tropones with γ-methylidene-δ-valerolactones. Mechanistic studies and density functional theory calculations disclosed that the divergent reactions stem from the different reaction profiles of the diastereomeric intermediates. While one undergoes either O- or C-allylation to provide [5.5.0] or [4.4.1] bicyclic compounds, the unique conformation of the other diastereomer allows an unconventional alkene isomerization to deliver bridgehead alkene-containing bicyclo[4.4.1] compounds. The conversion of these products to diverse complex polycyclic scaffolds has also been demonstrated.

Adjuvant chemoradiotherapy versus adjuvant chemotherapy for patients with N3 gastric cancer after D2/R0 resection: a retrospective study based on propensity score analyses.

Purpose: N3 gastric cancer (GC) is characterized by a heavy burden of lymph node metastasis and a high postoperative recurrence rate. The role of radiotherapy in this group of patients remains undetermined. The purpose of this study was to compare the effectiveness of adjuvant chemoradiotherapy (CRT) and adjuvant chemotherapy (ChT) for N3 GC after D2/R0 resection. Patients and methods: From January 2004 to December 2015, patients with N3 GC in the database of Fudan University Shanghai Cancer Center were retrospectively reviewed. The eligible patients were enrolled in an adjuvant CRT group and an adjuvant ChT group. Four different methods based on a propensity score model were used to balance the baseline characteristics. Then, survival analyses between the two groups were performed in addition to patterns of recurrence and subgroup analyses. Results: In total, 175 and 365 eligible patients were enrolled into the CRT and ChT groups, respectively. After balancing, the disease-free survival (DFS) of patients in the CRT group was significantly better than that of patients in the ChT group (p=0.021). Subgroup analyses showed that patients with N3a GC benefitted from adjuvant CRT. Conclusion: Compared with adjuvant ChT, adjuvant CRT can further improve the DFS of patients with N3 GC after D2/R0 resection. Patients with lymph node metastases should be further stratified when selecting patients for adjuvant CRT.

[Clinical analysis of 168 cases of multiple primary colorectal carcinoma].

OBJECTIVE: To study the incidence rate of multiple primary colorectal carcinomas (MPCC) in colorectal carcinoma and to evaluate its clinical and pathological characteristics. METHODS: One hundred and sixty-eight (4.6%) patients from 3663 cases with colorectal carcinoma were diagnosed with MPCC from January 1985 to December 2003. The clinical data of the patients were collected retrospectively to investigate the diagnosis and treatment of MPCC. RESULTS: Of the 168 patients, 81 were diagnosed as synchronous colorectal carcinoma (SC), 72 with metachronous colorectal carcinoma (MC), 15 with both SC and MC. The median age at time of diagnosis of colorectal carcinoma was 58 years old (range from 20 to 82 years old). Three hundred and ninety-three cancer lesions were detected in these 168 cases (mean, 2.3 lesions/case). The rectum and sigmoid colon were the most involved sites (61.6%). Eighteen cases (10.7%) were verified with hereditary non-polyposis colorectal cancer (HNPCC) while another 9 cases were highly suspected. Fourteen patients (8.3%) were found with other malignancies out of large intestine, 41 patients (24.4%) with colorectal adenomas, 72 (42.9%) with adenoma carcinogenesis. Among the 96 SC patients, 91 were given preoperative colonoscopy and 65 (71.4%) got the diagnosis. All the MC patients were diagnosed by postoperative colonoscopy. The overall 5-year survival rate of the 168 patients was 69.8%. CONCLUSIONS: MPCC should be paid more attention in colorectal cancer management. Colonoscopic surveillance is much more important in diagnosis and follow-up of MPCC for reducing the misdiagnosis of SC and detecting more MC in time. Prompt treatment of adenoma can reduce the occurrence of MPCC, and active and standard surgical treatment should be done for MPCC.

MiR-374b Promotes Proliferation and Inhibits Apoptosis of Human GIST Cells by Inhibiting PTEN through Activation of the PI3K/Akt Pathway.

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. In order to investigate a new treatment fot GIST, we hypothesized the effect of miR-374b targeting PTEN gene-mediated PI3K/Akt signal transduction pathway on proliferation and apoptosis of human gastrointestinal stromal tumor (GIST) cells. We obtained GIST tissues and adjacent normal tissues from 143 patients with GIST to measure the levels of miR-374b, PTEN, PI3K, Akt, caspase9, Bax, MMP2, MMP9, ki67, PCNA, P53 and cyclinD1. Finally, cell viability, cell cycle and apoptosis were detected. According to the KFGG analysis of DEGs, PTEN was involved in a variety of signaling pathways and miRs were associated with cancer development. The results showed that MiR-374b was highly expressed, while PTEN was downregulated in the GIST tissues. The levels of miR-374b, PI3K, AKT and PTEN were related to tumor diameter and pathological stage. Additionally, miR-374b increased the mRNA and protein levels of PI3K, Akt, MMP2, MMP9, P53 and cyclinD1, suggesting that miR-374b activates PI3K/Akt signaling pathway in GIST-T1 cells. Moreover, MiR-374b promoted cell viability, migration, invasion, and cell cycle entry, and inhibited apoptosis in GIST cells. Taken together, the results indicated that miR-374b promotes viability and inhibits apoptosis of human GIST cells by targeting PTEN gene through the PI3K/Akt signaling pathway. Thus, this study provides a new potential target for GIST treatment.

Adjuvant chemoradiotherapy versus adjuvant chemotherapy for R1 resected gastric cancer: a retrospective cohort study.

OBJECTIVE: The aim of this study was to compare the effects of adjuvant chemoradiotherapy (CRT) and adjuvant chemotherapy (ChT) on the survival of locally advanced gastric cancer (LAGC) patients treated with R1 resection. METHODS: The patients with LAGC and microscopically positive margins after a potentially curative gastrectomy in Fudan University Shanghai Cancer Centre were retrospectively identified. The patients who were referred to our hospital for adjuvant CRT after an R1 resection elsewhere were also included. The patients were divided into either the CRT group or ChT group according to the treatment strategy. We, then, examined the patient survival results and patterns of recurrence for each group. RESULTS: There were 114 LAGC patients treated with an R1 resection identified (CRT, n = 33; ChT, n = 81). The baseline characteristics between the two groups were not different. The estimated 3 year recurrence-free survival and overall survival in the CRT and ChT groups were 45.1% vs 31.8% (p = 0.09) and 49.6% vs 39.4% (p = 0.20), respectively. The results indicated that only nodal status was an independent prognostic factor (hazard ratio 4.04, 95% confidence interval 2.06-7.93). The risk of locoregional recurrence was increased in the ChT group. The subgroup analysis revealed that patients with pN0-2 GC showed a better recurrence-free survival due to adjuvant CRT (hazard ratio 0.19, 95% confidence interval 0.04-0.90; p = 0.022). CONCLUSION: Adjuvant CRT improves locoregional control and may benefit patients with pN0-2 GC after R1 resection. The nodal status may be the most important predictor for patient selection. Advances in knowledge: Nodal status may be the most important predictor for patient selection. Compared with adjuvant ChT, LAGC patients with pN0-2 disease may further benefit from additional radiotherapy after R1 resection.

Hypoxia/IL-1α axis promotes gastric cancer progression and drug resistance.

OBJECTIVE: The microenvironment of tumors constitutes a unique niche that promotes cancer metastasis and resistance. Two remarkable characteristics of this microenvironment are hypoxia and inflammation. Interleukin-1α (IL-1α), an important inflammatory factor, is frequently upregulated in a variety of cancers. This study aimed to investigate the expression of IL-1α in gastric cancer (GC) and explore the relationship between IL-1α and hypoxia. METHODS: Reverse-transcription polymerase chain reaction was performed to characterize IL-1α expression in different GC cell lines under normoxia or hypoxia. IL-1α expression was characterized in relation to tumor stage and lymph node metastasis of GC and the survival of patients. The effect of IL-1α knockdown under normoxia or hypoxia on cell proliferation, migration and sensitivity to cisplatin was also evaluated. Additionally, hypoxia-inducible factor-1α (HIF-1α) expression in KATO-III cells was either upregulated by ectopic HIF-1α expression or downregulated through shHIF-1α transfection, the effects of which on IL-1α expression was subsequently evaluated. RESULTS: There was a positive correlation between IL-1α, which was upregulated during hypoxia, and tumor stage, lymph node metastasis and resistance to cisplatin in GC. IL-1α was regulated by HIF1α, and a change in HIF1α expression altered the tumor-promoting effect of IL-1α. CONCLUSION: The IL-1α/hypoxia axis may be a valuable target for diagnosis and treatment of GC.

CXCR6 predicts poor prognosis in gastric cancer and promotes tumor metastasis through epithelial-mesenchymal transition.

Chemokines and their receptors have been confirmed to be involved in several types of cancer. However, little is known concerning the role of CXCL16 and its receptor CXCR6 in gastric cancer (GC) progression and metastasis. In the present study, expression of CXCL16 and CXCR6 in GC tumor and peritumoral tissues was detected by immunohistochemistry (IHC) in a cohort of 352 GC patients who underwent gastrectomy, and the correlation between CXCL16/CXCR6 expression and clinicopathological characteristics was further analyzed. To evaluate the function of CXCR6, we overexpressed and knocked down CXCR6 in GC cell lines. Results showed that expression of CXCR6, but not CXCL16, was significantly upregulated in GC tumor tissues, and was significantly correlated with lymph node and distant metastases, and advanced clinical stage in the GC patients. Survival analysis showed that large tumor size (>5 cm), elevated preoperative serum carcinoembryonic antigen (CEA) level, advanced TNM stage and high CXCR6 expression indicated worse overall survival (OS) and disease-free survival (DFS) in GC, and CXCR6 was an independent predictor for both OS and DFS in GC. In vitro experiments showed that CXCR6 overexpression induced cell migration and invasion ability, and promoted epithelial-mesenchymal transition of GC cells by upregulation of mesenchymal markers and inhibition of epithelial markers. In contrast, knockdown of CXCR6 in GC cells resulted in inhibition of cell proliferation, migration and invasion ability, and reversal of epithelial-mesenchymal transition (EMT) phenomenon. Our results demonstrated that CXCR6 is an independent prognostic factor for poor survival in GC patients, and may promote GC metastasis through EMT.