Inhibition of autophagy induced by tetrandrine promotes the accumulation of reactive oxygen species and sensitizes efficacy of tetrandrine in pancreatic cancer.

Pancreatic cancer, characterized by its poor prognosis, exhibits a marked resistance to conventional chemotherapy and immunotherapy, underscoring the urgent need for more effective treatment modalities. In light of this, the present study is designed to assess the potential antineoplastic efficacy of a combined regimen involving tetrandrine, a plant-derived alkaloid, and autophagy inhibitors in the context of pancreatic cancer. Electron microscopy and immunoblots showed that tetrandrine promoted the formation of autophagosomes and the upregulation of LC3II and the downregulation of p62 expression, indicating that tetrandrine induced autophagy in pancreatic cancer cells. Western blot revealed that tetrandrine inhibited the phosphorylation of AKT and mTOR, as well as the expression of Bcl-2, while upregulating Beclin-1 expression. Moreover, tetrandrine promoted the transcription and protein expression of ATG7. Following the combination of autophagy inhibitors and tetrandrine, the apoptotic rate and cell death significantly increased in pancreatic cancer cells. Consistent results were obtained when ATG7 was silenced. Additionally, tetrandrine induced the generation of ROS, which was involved in the activation of autophagy and apoptosis. Further investigation revealed that upon autophagy inhibition, ROS accumulated in pancreatic cancer cells, resulting in decreased mitochondrial membrane potential and further induction of apoptosis. The results of treating subcutaneous xenograft tumors with a combination of tetrandrine and chloroquine validated that autophagy inhibition enhances the toxicity of tetrandrine against pancreatic cancer in vivo. Altogether, our study demonstrates that tetrandrine induces cytoprotective autophagy in pancreatic cancer cells. Inhibiting tetrandrine-induced autophagy promotes the accumulation of ROS and enhances its toxicity against pancreatic cancer.

Gambogic acid induces autophagy and combines synergistically with chloroquine to suppress pancreatic cancer by increasing the accumulation of reactive oxygen species.

BACKGROUND: Gambogic acid is a natural component isolated from gamboge that possesses anticancer properties. Our previous study suggested that gambogic acid might be involved in autophagy; however, its role in pancreatic cancer remained unclear. METHODS: Cell viability and apoptosis of pancreatic cancer cell lines were determined using (4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan and flow cytometry. The effects of gambogic acid on autophagy was assessed by western blot, acridine orange staining, transmission electron microscopy, and measurement of autophagic flux through RFP-GFP-LC3 lentiviral transfection. The mitochondrial membrane potential was assessed by JC-1 staining. The production of reactive oxygen species was measured using CM-H2DCFDA staining. A xenograft tumor model of pancreatic cancer was created to determine the efficacy of gambogic acid and chloroquine. RESULTS: Gambogic acid induced the expression of LC3-II and Beclin-1 proteins in pancreatic cancer cells, whereas the expression of P62 showed a decline. Gambogic acid also increased the formation of both acidic vesicular organelles and autophagosomes, and increased autophagic flux. These findings indicated that gambogic acid induced the autophagic process. Furthermore, inhibition of autophagy by chloroquine or 3-methyladenine, or knockdown of Atg-7 all enhanced the cytotoxicity of gambogic acid, suggesting that gambogic acid-induced autophagy improves the survival of pancreatic cancer cells. Moreover, gambogic acid reduced the mitochondrial membrane potential and promoted ROS production, which contributed to the activation of autophagy. The inhibition of autophagy by chloroquine further reduced the mitochondrial membrane potential and increased the accumulation of ROS. This indicated that the inhibition of autophagy could mitigate the cellular protective effects induced by gambogic acid. The treatment combination of gambogic acid and chloroquine synergistically inhibited tumor growth in the xenograft tumor model. CONCLUSIONS: These results demonstrate that gambogic acid induces cytoprotective autophagy in pancreatic cancer cells. The inhibition of autophagy promotes the cytotoxicity of gambogic acid by increasing the accumulation of ROS in pancreatic cancer cells. Combining chloroquine and gambogic acid may be a promising treatment for pancreatic cancer.

[Meta-analysis of adjuvant chemotherapy on prognosis for gastric cancer patients after D2 dissection].

OBJECTIVE: To evaluate efficacy of adjuvant chemotherapy after D2 dissection on survival for patients with gastric cancer. METHODS: Randomized clinical trials (RCT) that compared adjuvant chemotherapy after D2 dissection with D2 dissection alone for gastric cancer were searched with Pubmed, Cochrane, Embase and CBM databases. Eligible trials published between 1990 and 2012 were included in the study. The quality of RCTs was assessed by the Jadad scale. Data synthesis and statistical analysis were performed by RevMan 5.1 software. RESULT: Eight RCTs with 3633 patients were included in this study. Among them, 1824 patients received adjuvant chemotherapy and 1809 patients didn't. Adjuvant chemotherapy was associated with a significant benefit in terms of overall survival (RR = 0.76, 95% CI: 0.69-0.84), disease free survival (RR = 0.72, 95%CI: 0.66-0.80) and recurrence rate (RR = 0.69, 95% CI: 0.62-0.77). CONCLUSION: Adjuvant chemotherapy was associated with survival benefit for gastric cancer after D2 dissection.

Umbelliprenin induces autophagy and apoptosis while inhibits cancer cell stemness in pancreatic cancer cells.

BACKGROUND: Umbelliprenin is a sesquiterpene coumarin isolated from Artemisia absinthium L. and shows antitumor effects in various cancers by inducing apoptosis. However, the antitumor effect of umbelliprenin in human pancreatic cancer has not been clarified. METHODS: The antitumor effects were determined by MTT and AnnexinV/PI double staining assay in vitro and xenograft mice in vivo. Autophagy was determined via immunofluorescence analysis. Apoptotic or autophagic related proteins were measured by immunoblotting. The pancreatic cancer cell stemness were determined by mammosphere formation and ALDEFLUOR assay. RESULTS: It revealed that umbelliprenin inhibited pancreatic cancer cell proliferation in vitro and pancreatic cancer tumor growth in vivo. Moreover, umbelliprenin induced pancreatic cancer cell BxPC3 apoptosis and autophagy as evidenced by upregulated apoptosis and autophagy- related protein expression (p < 0.01). Blocking autophagy by 3-MA or Atg7 knockout enhanced umbelliprenin-induced apoptosis (p < 0.05). Umbelliprenin also reduced pancreatic cancer cell stemness by reducing Oct4, Nanog, and Sox2 mRNA levels (p < 0.01). Mechanistically, umbelliprenin greatly inhibited Akt/mTOR and Notch1 signal pathway. CONCLUSION: Umbelliprenin may be a novel therapeutic approach for pancreatic cancer treatment.

Oral Delivery of Bioactive Glass-Loaded Core-Shell Hydrogel Microspheres for Effective Treatment of Inflammatory Bowel Disease.

Resolving inflammation and promoting intestinal tissue regeneration are critical for inflammatory bowel disease (IBD) treatment. Bioactive glass (BG) is a clinically approved bone graft material and has been shown to modulate inflammatory response, but it is unknown whether BG can be applied to treat IBD. Here, it is reported that BG attenuates pro-inflammatory response of lipopolysaccharide (LPS)-stimulated macrophages and hence reduces inflammatory damage to intestinal organoids in vitro. In addition, zein/sodium alginate-based core-shell microspheres (Zein/SA/BG) are developed for oral delivery of BG, which helps prevent premature dissolution of BG in the stomach. The results show that Zein/SA/BG protects BG from a gastric-simulated environment while dissolved in an intestinal-simulated environment. When administered to acute and chronic colitis mice model, Zein/SA/BG significantly reduces intestinal inflammation, promotes epithelial tissue regeneration, and partially restores microbiota homeostasis. These findings are the first to reveal the therapeutic efficacy of BG against IBD, which may provide a new therapeutic approach at low cost for effective IBD treatment.

Jumonji-C domain-containing protein 5 suppresses proliferation and aerobic glycolysis in pancreatic cancer cells in a c-Myc-dependent manner.

Despite the importance of metabolic reprogramming in cancer cells, the molecular mechanism regulating the tumor metabolic shift is still poorly understood. Deregulation of Jumonji-C domain-containing protein 5 (JMJD5) has been associated with multiple facets of biological processes in cancer cells. However, the role of JMJD5 in pancreatic cancer cells has seldom been discussed and requires further investigation. In the present study, by silencing or overexpressing JMJD5 in pancreatic cancer cells, we examined the impact of JMJD5 on cell proliferation and glucose metabolism. Using a dual luciferase assay, we assessed the effect of JMJD5 on the transcriptional activity of the c-Myc target gene. Analyzing The Cancer Genome Atlas and the Gene Expression Omnibus datasets revealed that low JMJD5 expression was associated with poor prognosis in patients with pancreatic cancer. JMJD5 loss promoted pancreatic cancer cell proliferation and induced a cellular metabolic shift from oxidative phosphorylation to glycolysis. In addition, in vivo experiments confirmed that ectopic JMJD5 expression inhibited cancer cell growth and the expression of glycolytic enzymes, such as lactate dehydrogenase and phosphoglycerate kinase 1. Moreover, JMJD5 negatively regulated c-Myc expression, the main regulator of cancer metabolism, leading to decreased c-Myc-targeted gene expression. Overall, the present study indicated that decreased JMJD5 expression promoted cell proliferation and glycolytic metabolism in pancreatic cancer cells in a c-Myc-dependent manner.

Deciphering and engineering tissue folding: A mechanical perspective.

The folding of tissues/organs into complex shapes is a common phenomenon that occurs in organisms such as animals and plants, and is both structurally and functionally important. Deciphering the process of tissue folding and applying this knowledge to engineer folded systems would significantly advance the field of tissue engineering. Although early studies focused on investigating the biochemical signaling events that occur during the folding process, the physical or mechanical aspects of the process have received increasing attention in recent years. In this review, we will summarize recent findings on the mechanical aspects of folding and introduce strategies by which folding can be controlled in vitro. Emphasis will be placed on the folding events triggered by mechanical effects at the cellular and tissue levels and on the different cell- and biomaterial-based approaches used to recapitulate folding. Finally, we will provide a perspective on the development of engineering tissue folding toward preclinical and clinical translation. STATEMENT OF SIGNIFICANCE: Tissue folding is a common phenomenon in a variety of organisms including human, and has been shown to serve important structural and functional roles. Understanding how folding forms and applying the concept in tissue engineering would represent an advance of the research field. Recently, the physical or mechanical aspect of tissue folding has gained increasing attention. In this review, we will cover recent findings of the mechanical aspect of folding mechanisms, and introduce strategies to control the folding process in vitro. We will also provide a perspective on the future development of the field towards preclinical and clinical translation of various bio fabrication technologies.

Survival of pancreatic cancer patients is negatively correlated with age at diagnosis: a population-based retrospective study.

In this population-based retrospective study, we aimed to investigate the association between age at diagnosis and prognosis of pancreatic cancer (PC) patients using data from the National Cancer Institute's Surveillance, Epidemiology, and the End Results database. Different factors for stratification, like race, sex, year of diagnosis, pathological grade, American Joint Committee on Cancer stage, historic stage, and tumour location, were included to compare the survival rates of patients of different age groups, and the five-year survival rate was calculated. Multivariate analysis using Cox regression was performed to control for confounder bias, and the hazard ratio was calculated. In total, 126,066 patients were enrolled in this study. The five-year PC-specific survival of patients aged 20-40 years was almost three times that of patients aged >40 years. Stratified by race, sex, year of diagnosis, pathological grade, clinical stage, and tumour location, a descending trend of survival was observed with an increase in age. On multivariate analysis, the mortality risk of PC patients aged 40-80 years was twice that of patients aged <40 years; however, patients aged >80 years had a mortality risk three times that of patients aged <40 years. The survival rate of PC patients has improved in the last few decades. Age at diagnosis is a significant and negative prognostic factor for PC, and patients diagnosed at a relatively earlier stage had the best survival.

Combined Exosomal GPC1, CD82, and Serum CA19-9 as Multiplex Targets: A Specific, Sensitive, and Reproducible Detection Panel for the Diagnosis of Pancreatic Cancer.

Pancreatic cancer is a highly lethal malignancy with poor prognosis due to the lack of early symptoms and resultant late diagnosis. Thus, it is extremely urgent to establish a simple and effective method for the early diagnosis of pancreatic cancer. Although some studies have provided positive evidence for the use of exosomal surface protein glypican-1 (GPC1) as a biomarker for early screening, its clinical application is still controversial. Here, we systematically verified the role of exosomal GPC1 as a potential screening biomarker. First, bottleneck problems of a stable detection method and an identification standard were systematically studied, and a Python-based standardized data processing method was established to analyze exosomal GPC1 expression. Second, a detection panel consisting of exosomal GPC1, exosomal cluster of differentiation 82 (CD82), and serum carbohydrate antigen 19-9 (CA19-9) was employed for pancreatic cancer detection. This panel exhibited excellent diagnostic results (AUC = 0.942) and could effectively distinguish healthy people from patients with pancreatic cancer (P value threshold = 0.2282) and patients with pancreatitis from patients with pancreatic cancer (P value threshold = 0.5467). IMPLICATIONS: These results indicate that the combined detection of exosomal GPC1, exosomal CD82, and serum CA19-9 shows great promise as a standard method for pancreatic cancer detection and that this panel could be further applied for screening pancreatic cancer in Chinese populations.

A C-X-C Chemokine Receptor Type 2-Dominated Cross-talk between Tumor Cells and Macrophages Drives Gastric Cancer Metastasis.

PURPOSE: C-X-C chemokine receptor type 2 (CXCR2) is a key regulator that drives immune suppression and inflammation in tumor microenvironment. CXCR2-targeted therapy has shown promising results in several solid tumors. However, the underlying mechanism of CXCR2-mediated cross-talk between gastric cancer cells and macrophages still remains unclear.Experimental Design: The expression of CXCR2 and its ligands in 155 human gastric cancer tissues was analyzed via immunohistochemistry, and the correlations with clinical characteristics were evaluated. A coculture system was established, and functional assays, including ELISA, transwell, cell viability assay, and qPCR, were performed to determine the role of the CXCR2 signaling axis in promoting gastric cancer growth and metastasis. A xenograft gastric cancer model and a lymph node metastasis model were established to study the function of CXCR2 in vivo. RESULTS: CXCR2 expression is associated with the prognosis of patients with gastric cancer (P = 0.002). Of all the CXCR2 ligands, CXCL1 and CXCL5 can significantly promote migration of gastric cancer cells. Macrophages are the major sources of CXCL1 and CXCL5 in the gastric cancer microenvironment, and promote migration of gastric cancer cells through activating a CXCR2/STAT3 feed-forward loop. Gastric cancer cells secrete TNF-α to induce release of CXCL1 and CXCL5 from macrophages. Inhibiting CXCR2 pathway of gastric cancer cells can suppress migration and metastasis of gastric cancer in vitro and in vivo. CONCLUSIONS: Our study suggested a previously uncharacterized mechanism through which gastric cancer cells interact with macrophages to promote tumor growth and metastasis, suggesting that CXCR2 may serve as a promising therapeutic target to treat gastric cancer.

Autophagy Inhibition Promotes Bevacizumab-induced Apoptosis and Proliferation Inhibition in Colorectal Cancer Cells.

Aim: Anti-VEGF therapy plays an important role in the treatment of malignant tumors, especially metastatic malignant tumors. However, resistance and an inefficient response to anti-VEGF therapy exist. The current study aimed to investigate whether autophagy plays a part in the anti-tumor effect of bevacizumab in colorectal cancer cells. Methods: VEGF-A expression was measured by immunohistochemical methods. Cell viability and cell apoptosis were detected using 3-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) and flow cytometry. Autophagy was assessed by a western blot, fluorescence microscopy and transmission electron microscopy. HIF-1α was measured using a western blot. A xenograft tumor model of colorectal cancer was constructed to determine the efficacy of the treatment of bevacizumab and chloroquine. Results: VEGF-A protein was upregulated in colorectal cancer tissue. Anti-VEGF (bevacizumab) inhibited cell viability and induced apoptosis. Moreover, bevacizumab induced autophagy. The inhibition of autophagy by chloroquine or by small interfering RNA promoted bevacizumab-induced apoptosis and proliferation inhibition. Further study showed that bevacizumab treatment significantly augmented HIF-1α. Furthermore, cells pretreated with YC-1, a HIF-1α inhibitor, displayed significantly attenuated bevacizumab-induced autophagy. Finally, a combinatory treatment of bevacizumab and chloroquine synergistically inhibited tumor growth in a xenograft tumor model of colorectal cancer cells. Conclusions: Our results showed that the inhibition of autophagy promoted the anti-tumor effect of bevacizumab and may offer a promising therapeutic strategy for colorectal cancer.

Localized Controlled Delivery of Gemcitabine via Microsol Electrospun Fibers to Prevent Pancreatic Cancer Recurrence.

The low radical surgery rate of pancreatic cancer leads to increased local recurrence and poor prognosis. Gemcitabine (GEM) is the preferred chemotherapeutic for pancreatic cancer. However, systemic chemotherapy with GEM has reached a bottleneck due to its serious side effects after frequent injections. In this study, GEM is successfully enwrapped into electrospun fibers via microsol electrospinning technology to form a stable core-shell fibrous structure. The GEM release rate can be adjusted by altering the thickness of the hyaluronan-sol inner fiber and the quantity of loaded GEM, and the release can be sustained for as long as three weeks. In vitro assays show that these electrospun fibers effectively inhibit pancreatic cancer cells and promote apoptosis. In vivo studies show that the fibrous membranes are better for inhibiting the growth of residual tumors than that of integrated tumors. Furthermore, immunohistochemistry results show that GEM-loaded fibers promote a higher cell apoptosis rate than does systemically injected GEM in residual tumors. In addition, the local delivery of GEM with fibers significantly reduces liver toxicity. In summary, a core-shell electrospun fiber for the controlled and localized delivery of GEM, which greatly improves the treatment of residual tumors and prevents pancreatic tumor recurrence, is developed.

Gambogic acid sensitizes gemcitabine efficacy in pancreatic cancer by reducing the expression of ribonucleotide reductase subunit-M2 (RRM2).

BACKGROUND: Pancreatic cancer is susceptible to gemcitabine resistance, and patients receive less benefit from gemcitabine chemotherapy. Previous studies report that gambogic acid possesses antineoplastic properties; however, to our knowledge, there have been no specific studies on its effects in pancreatic cancer. Therefore, the purpose of this study was to explore whether increases the sensitivity of pancreatic cancer to gemcitabine, and determine the synergistic effects of gambogic acid and gemcitabine against pancreatic cancer. METHODS: The effects of gambogic acid on cell viability, the cell cycle, and apoptosis were assessed using 4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) and flow cytometry in pancreatic cancer cell lines. Protein expression was detected by western blot analysis and mRNA expression was detected using q-PCR. A xenograft tumor model of pancreatic cancer was used to investigate the synergistic effects of gambogic acid and gemcitabine. RESULTS: Gambogic acid effectively inhibited the growth of pancreatic cancer cell lines by inducing S-phase cell cycle arrest and apoptosis. Synergistic activity of gambogic acid combined with gemcitabine was observed in PANC-1 and BxPC-3 cells based on the results of MTT, colony formation, and apoptosis assays. Western blot results demonstrated that gambogic acid sensitized gemcitabine-induced apoptosis by enhancing the expression of cleaved caspase-3, cleaved caspase-9, cleaved-PARP, and Bax, and reducing the expression of Bcl-2. In particular, gambogic acid reduced the expression of the ribonucleotide reductase subunit-M2 (RRM2) protein and mRNA, a trend that correlated with resistance to gemcitabine through inhibition of the extracellular signal-regulated kinase (ERK)/E2F1 signaling pathway. Treatment with gambogic acid and gemcitabine significantly repressed tumor growth in the xenograft pancreatic cancer model. Immunohistochemistry results demonstrated a downregulation of p-ERK, E2F1, and RRM2 in mice receiving gambogic acid treatment and combination treatment. CONCLUSIONS: These results demonstrate that gambogic acid sensitizes pancreatic cancer cells to gemcitabine in vitro and in vivo by inhibiting the activation of the ERK/E2F1/RRM2 signaling pathway. The results also indicate that gambogic acid treatment combined with gemcitabine might be a promising chemotherapy strategy for pancreatic cancer.

In vitro and in vivo combined antibacterial effect of levofloxacin/silver co-loaded electrospun fibrous membranes.

Post-surgery mesh infections are one of the most common complications of hernia repair at the interface of implant materials and tissue, because high doses of antimicrobial agents are toxic and low doses of antibacterial agents are ineffective, with no good clinical solution currently available. To reduce the infection rates after mesh implantation, we designed a "one-pot synthesized" mesoporous silica nanoplatform consisting of levofloxacin (Lev) and silver (Lev@MSN@Ag) composites with poly-l-lactide (PLLA) electrospun fibrous membranes via blending electrospinning. With advances in the combined antibacterial agents Lev and Ag at a low dosage for the treatment of drug-resistant bacterial infections (28 µg mL-1 Lev and 12 µg mL-1 Ag) with a concentration of 5 × 105 CFU mL-1, the composite electrospun fibers act as a carrier for drug-loading and have an antibacterial effect over 8 weeks. Lev@MSN@Ag-PLLA fibers showed a superior antibacterial effect on drug resistant strains in the in vitro test at low doses of antibacterial agents. Further, the in vivo study showed that Lev@MSN@Ag-PLLA fibers significantly inhibited bacterial growth and infection over 8 weeks through the combined effect of low dosage antibacterial drugs. In conclusion, the Lev@MSN@Ag-PLLA fibers provided an advanced combined antibacterial nanoplatform of low dosage for the treatment of drug-resistant bacterial infections.

Correlation between smoking history and molecular pathways in sporadic colorectal cancer: a meta-analysis.

BACKGROUND: Epidemiological studies have shown that smoking increases the risk for colorectal cancer (CRC). Evidence of the guiding significance of smoking history for molecular classification and molecular targeted anti-tumor therapy is not well established. AIMS: To provide indirectly evidence, we conducted a systematic meta-analysis of association between smoking history and different molecular classification. METHODS: We searched in multiple databases up to January 2014, and identified 27 eligible studies. All studies were divided into seven groups based on different molecular alteration categories, which are MSI, CIMP, and three molecular pathway-associated gene alterations (APC, KRAS, P53, BRAF mutation, and APC methylation). Crude odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated to evaluate the association. RESULTS: Smoking showed a significantly positive correlation with P53 mutation (exons 4 to 8), BRAF (codon 600) mutation, MSI positivity, and CIMP positivity, with ORs of 1.25 (95% CI: 1.07-1.45), 1.41 (95% CI: 1.18-1.68), 1.28 (95% CI: 1.12-1.47), and 1.23 (95% CI: 1.01-1.50), respectively. However, smoking was not positively correlated with APC (mutation cluster region) and KRAS (codons 12 and 13) mutation in sporadic CRC patients. CONCLUSIONS: These findings suggested smoking history occurred with P53 mutation, BRAF mutation, MSI positivity, and CIMP positivity in sporadic CRCs; and could guide those specifically therapeutic designs when molecular classification with genetic test was infeasible. More associated studies should be conducted for strengthening and renewing the current result.

CXCL1 expression is correlated with Snail expression and affects the prognosis of patients with gastric cancer.

Gastric cancer (GC) continues to result in a poor survival rate and prognostic biomarkers for the disease are lacking. Chemokine (C-X-C motif) ligand (CXCL1) expression plays a critical role in tumor metastasis, and Snail promotes epithelial-mesenchymal transition (EMT) to promote metastasis. Therefore, the present study aimed to investigate the correlation between CXCL1 and Snail expression and the effect of CXCL1 expression on the survival of patients with GC. CXCL1 and Snail expression in paraffin-embedded tissue sections from 127 patients with GC were each assessed by immunohistochemistry. Cox regression and Kaplan-Meier analyses were performed to evaluate the prognostic significance of CXCL1 and Snail. Evaluation of the association between CXCL1 and Snail expression and clinical characteristics was based on the χ2 test. Spearman's rank correlation coefficient and Fisher's exact test were used to explore the association between CXCL1 and Snail expression in GC tissues. CXCL1 was found to be significantly associated with tumor invasion (P=0.003), tumor-node-metastasis (TNM) staging (P=0.001), tumor size (P=0.013) and lymph node metastasis (P=0.022) in GC. Snail overexpression was also significantly associated with tumor invasion (P=0.001), TNM staging (P=0.005), tumor size (P=0.026), lymph node metastases (P=0.014) and perineural invasion (P=0.009). CXCL1 and Snail expression were independent factors for a worse overall survival rate, as determined by multivariate analysis (P=0.011 and P=0.018; respectively). The combined expression of CXCL1 and Snail resulted in a worse prognosis compared with the other three groups (P=0.005). Furthermore, there was a significantly positive correlation between CXCL1 and Snail expression in GC (r=0.431; P<0.001). The expression of CXCL1 is significantly associated with Snail expression and may be used as a predictive co-biomarker for patient prognosis and tumor aggressiveness in GC. CXCL1 may promote GC metastasis by regulating EMT.