Depleting ABCE1 expression induces apoptosis and inhibits the ability of proliferation and migration of human esophageal carcinoma cells

Objective: This study aims to explore the clinical characteristics of ABCE1 in esophageal cancers and its roles in the proliferation, invasiveness, migration and apoptosis of the esophageal carcinoma Eca109 cell line. Methods: The expression of ABCE1 and its target protein-RNase L, were first studied in tumor tissues of esophageal carcinoma and adjacent non-tumor tissues. The siRNA green fluorescent protein (GFP) expression vector of ABCE1 was prepared and transfected into the esophageal carcinoma Eca109 cells, then the fluorescence microscope was used to study the transfection efficiency. The MTT assay, cell invasion, the transwell and scratch assay were used to study cell proliferation and migration activity; the apoptosis rate was tested by flow cytometry. Western blot and RT-PCR assay were adopted to measure their silencing efficacy. Results: ABCE1 expression is low in the adjacent non-tumor tissues while the expression is high in the esophageal carcinoma; the expression is reversely proportional to the differentiation degrees. The expression of RNase L was in contrary to ABCE1. After transfected with ABCE1-siRNA, the proliferation, invasiveness and migration capabilities of cells decreased significantly whilst the apoptosis rate enhanced greatly (P<0.01). Meanwhile, the expression of ABCE1 in Eca109 cells was blocked (P<0.01) while the expression of RNase L increased significantly (P<0.01). Conclusion: ABCE1 is closely connected with the pathogenesis and development of esophageal carcinoma, which act through the cellular pathways of 2-5A/RNase L.     

Upregulated SLC1A5 promotes cell growth and survival in colorectal cancer

Glutamine metabolism is essential for tumorigenesis of colorectal cancer, cancer cells remodel their glutamine metabolic pathways to fuel rapid proliferation. SLC1A5 is an important transporter of glutamine various cancer cells. In this study, we investigated SLC1A5 protein expression in colorectal cancer and evaluated its clinical significance and functional importance. Immunohistochemical analysis was performed on tissue microarrays containing 90 pairs of cancer and adjacent normal tissues from colorectal cancer patients, we found that SLC1A5 expression increased significantly in colorectal cancer compared with normal mucosa tissues (P < 0.001). We further validated SLC1A5 overexpression in 12 pairs of fresh cancer and adjacent normal mucosa tissues from colorectal cancer patients by Western blot (P < 0.05). SLC1A5 expression levels were strongly associated with T stage of tumor (P < 0.05), and the tubular adenocarcinoma subtype (P < 0.001). Moreover, downregulation of SLC1A5 by synthetic siRNA could suppress proliferation and induce apoptosis in colorectal cancer cell lines HT29 and HCT116. In conclusion, our results provide for the first time the differential expression in human colorectal cancer and normal tissues, and a functional link between SLC1A5 expression and growth and survival of colorectal cancer, making it an attractive target in colorectal cancer treatment.     

The role of EphB4 and IGF-IR expression in breast cancer cells

Objective: to investigate the role of EphB4 and IGF-1R in the proliferation and migration of breast cancer. Methods: The relative mRNA levels of EphB4 were measured by RT-PCR. The proliferation of the cells was determined by MTT assay, and cells migration and invasive ability was analyzed using the scratch migration assay. Results: The expression of EphB4 in control group was significantly decreased when compared with IGF-I group (P < 0.001). The expression of EphB4 in IGF-I+LY and LY group were lower than that of the control group (P < 0.001).The cell proliferation and migration ability of the cells in IGF-I group increased significantly compared to the cells in the control group (P < 0.001), while the cells in IGF-1+LY group and LY group showed a decreased proliferation and migration ability compared to the control group (P < 0.001). Conclusion: IGF-IR might be a upstream gene of EphB4. Besides, higher expression of EphB4 shows increased tumor proliferation and migration in breast cells. The study of EphB4 upstream gene and signaling pathway can provide more targeted anti-tumor point selection for targeted therapy.     

Roles of the miR-139-5p/CCT5 axis in hepatocellular carcinoma: a bioinformatic analysis

Background: MiRNAs are pivotal regulators involved in proliferation, apoptosis, invasion, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, drug resistance and autophagy in hepatocellular carcinoma (HCC). The aim of this study was to investigate the influence of miR-139-5p and its target genes on the outcomes of HCC.Methods: Survival analysis of miR-139-5p in HCC was conducted in Kaplan-Meier plotter. Target genes of miR-139-5p were identified in TargetScan, miRTarBase and starBase. Gene Expression Omnibus (GEO) series were used for the validation of miR-139-5p target genes. Cox proportional regression model was also established.Results: In Kaplan-Meier plotter, 163 HCC patients were included. MiR-139-5p downregulation was significantly associated with unfavorable overall survival (OS) and disease-free survival (DFS) in HCC patients (all P < 0.001). MiR-139-5p was significantly downregulated in HCC tumors and human hepatoma cell lines (all P < 0.05). As a target gene of miR-139-5p, CCT5 was overexpressed in HCC tumor tissues and peripheral blood mononuclear cells (all P < 0.05). A negative correlation between CCT5 and miR-139-5p was found in TCGA dataset. CCT5 overexpression was significantly associated with worse OS in HCC patients (P < 0.001), which was validated in the {"type":"entrez-geo","attrs":{"text":"GSE14520","term_id":"14520"}}GSE14520 dataset (P = 0.017). CCT5 mRNA was significantly overexpressed in HCC patients with alpha-fetoprotein (AFP) > 300 ng/ml, BCLC staging B-C, TNM staging III and main tumor size > 5 cm (all P < 0.05). According to the Cox regression model of CCT5-interacting genes, HCC patients with high risk had poor OS compared to those with low risk in the TCGA dataset (P < 0.001), with the 1-year, 3-year, and 5-year ROC curves of an area under the curve (AUC) equal to 0.704, 0.662, and 0.631, respectively.Conclusions: MiR-139-5p suppresses HCC tumor aggression and conversely correlated with CCT5. The miR-139-5p/CCT5 axis might perform crucial functions in the development of HCC.     

Knock-down of ABCE1 gene induces G1/S arrest in human oral cancer cells

Purpose: This study aims to explore the clinical characteristics of ATP binding cassette E1 (ABCE1) in oral squamous cell carcinomas (OSCC) and its roles in the proliferation, invasiveness, migration and apoptosis of the human oral squamous cell carcinoma cells CAL-27. Methods: The expression of ABCE1 and its target protein-RNase L, were first studied in tumor tissues of OSCC and adjacent non-tumor tissues. Moreover, CAL-27cells were transfected by ABCE1-specific shRNA, then MTT assay, the transwell and scratch assay were used to study cell proliferation and migration activity; the apoptosis rate and cell cycle distribution were tested by flow cytometry. Western blot and RT-PCR assay were adopted to measure their silencing efficacy. Results: ABCE1 expression is low in the adjacent non-tumor tissues while the expression is high in the oral cancer; the expression is reversely proportional to the differentiation degrees. The expression of RNaseL was in contrary to ABCE1. After transfected with ABCE1-siRNA, the proliferation, invasiveness and migration capabilities of cells decreased significantly whilst the apoptosis rate enhanced greatly (P < 0.01). Meanwhile, the expression of ABCE1 in CAL-27 cells was blocked (P < 0.01) while the expression of RNase L increased significantly (P < 0.01). Conclusion: ABCE1 is closely connected with the pathogenesis and development of oral cancer, which acts through the cellular pathways of 2-5A/RNase L.     

Significance of TLR4/MyD88 expression in breast cancer

Objective: To investigate the expression of TLR4/MyD88 in breast cancer, and explore the relationship between their expression and breast cancer tumor growth and invasion. Methods: We examined the protein expression of TLR4 and MyD88 in 60 cases of histologically confirmed breast cancer. The relationship of their protein expressions with clinical features including age at diagnosis, tumor size and stage, lymph node metastasis and distant metastasis were analyzed. Results: The IHC results showed that TLR4 and MyD88 were expressed in 63.3% (38/60) and 58.3% (35/60) of malignant breast tumors respectively. TLR4 expression in breast cancer were significantly higher than in fibroadenoma (n = 4, 20.0%) and adjacent normal tissues (n = 2, 10.0%) (P < 0.001). MyD88 expression in breast cancer were also significantly higher than in fibroadenoma (n = 4, 20.0%) and adjacent normal tissue (n = 3, 15.0%) (P < 0.001). The gene expressions of TLR4 and MyD88 were significantly higher in breast cancer than in fibroadenoma and adjacent normal tissues (P < 0.05). The protein expressions of TLR4 and MyD88 were also significantly associated with poor clinical features (P < 0.05). Conclusion: TLR4 and MyD88 expression might be associated with breast cancer growth and regional and distant metastases.     

High expression of long non-coding RNA ANRIL is associated with poor prognosis in hepatocellular carcinoma

Introduction: long non-coding RNA ANRIL (lncRNA ANRIL) has been demonstrated to play a crucial role in cancer progression. However, its effects in hepatocellular carcinoma (HCC) have not been explored. The aim of this study was to investigate the clinical significance of lncRNA NRIL in human HCC. Methods: In this study, we determined for the first time the expression of lncRNA ANRIL in human HCC by quantitative Real-time-PCR analysis. Kaplan-Meier curves and multivariate Cox proportional models were used to study the impact on clinical outcome. Small interfering RNA (siRNA) was used to silence lncRNA ANRIL and to explore the effects of reduced lncRNA ANRIL expression on cell growth and metastasis. Results: lncRNA ANRIL expression in HCC tissues was significantly higher than in the adjacent non-tumor tissues (P < 0.05). The expression of lncRNA ANRIL was remarkably associated with the histologic grade and TNM stage of HCC patients (P < 0.05). In addition, HCC patients with higher lncRNA ANRIL expression had significantly poorer overall survival (P < 0.05). Multivariate analysis suggested that high lncRNA ANRIL expression was an independent predictor of poor prognosis (P < 0.05). Moreover, in vitro assays revealed that the decreased expression of lncRNA ANRIL could suppress the cell proliferation, migration and invasion HCC cells. Conclusions: Our results suggest that lncRNA ANRIL may serve as an efficient clinical biomarker and a therapeutic target for HCC patients.     

Lin28B is a novel prognostic marker in gastric adenocarcinoma

Lin28B, a homologue of Lin28, represses biogenesis of let-7 microRNAs with a role in tumorigenesis and is considered a potential therapeutic target for various human cancers. The aim of the study was to identify the clinical significance of Lin28B in gastric adenocarcinoma (GAC). We examined the expression of Lin28B in 97 human gastric cancer samples with 32 samples of non-dysplastic tissues by immunohistochemistry. In the 97 GAC cases, 42 were with high Lin28B expression. The expression levels of Lin28B proteins in GAC were higher than in corresponding adjacent normal tissues (P=0.001). Significant correlations were noted between Lin28B expression and lymph node status (P=0.005), TNM stage (P < 0.001), tumor invasion (P=0.036), and differentiation (P=0.001) of GAC patients. The Kaplan-Meier estimates showed a negative correlation of overall 5-year survival rate with Lin28B expression where higher expression resulted in poorer prognosis in GAC. In univariate analysis, lymph node metastasis, TNM stage, serosal invasion, Lin28B expression as well as differentiation grade could predict the prognosis of GAC patients (P=0.002, P < 0.001, P=0.003, P < 0.001, P=0.001, respectively). Multivariate analysis revealed that the expression level of Lin28B (P < 0.001), TNM stage (P < 0.001) as well as differentiation grade (P < 0.001) were the three potential independent prognostic factors in our study [Hazard ratio (HR)=2.108 and P=0.017, HR=1.994 and P=0.018, HR=1.939 and P=0.046, respectively]. Our findings point to the prognostic role of Lin28B in GAC, and indicate Lin28B as a potential therapeutic target of GAC patients.     

Expression of RKIP,E-cadherin and NF-kB p65 in esophageal squamous cell carcinoma and their correlations

To detect the expression of RKIP, E-cadherin and NF-kB p65 in esophageal squamous cell carcinoma (ESCC) and study their correlations. Steptavidin-peroxidase (S-P) method was employed to detect the expressions of RKIP, E-cadherin and NF-kB p65 in ESCC tissues from 77 cases and paracancerous tissues from 77 cases. The correlations between their expressions and clinicopathological indices and between the expressions of these proteins themselves were analyzed. The expressions of RKIP and E-cadherin in ESCC tissues were obviously lower than those in the paracancerous tissues (P<0.01); the expressions in ESCC tissues from cases with lymph node metastasis were lower than those from cases without lymph node metastasis (P<0.01); the expression of RKIP was positively correlated with the expression of E-cadherin in ESCC tissues (P<0.01). The expression of NF-kB p65 in ESCC tissues was correlated with clinical staging, lymph node metastasis and tumor differentiation (P<0.01); the expression of RKIP was negatively correlated with the expression of NF-kB p65 in ESCC tissues (P<0.05). Downregulation or depletion of RKIP was related to the onset and progression of ESCC, and facilitated the invasion and metastasis of ESCC by downregulating E-cadherin and upregulating NF-kB p65.     

Up-regulation of long non-coding RNA Sox2ot promotes hepatocellular carcinoma cell metastasis and correlates with poor prognosis

Background: Long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in cancer biology, and the lncRNA Sox2ot is up-regulated in some tumors. However, the contributions of Sox2ot to hepatocellular carcinoma (HCC) remain largely unknown. Methods: In the present study, expression of lncRNA Sox2ot was evaluated by quantitative real-time PCR in tumor tissues and adjacent non-tumor tissues in 84 HCC patients. The association of lncRNA Sox2ot expression with clinicopathological features and the prognosis of HCC patients were also analyzed. Survival analysis was performed using the Kaplan-Meier method and Cox’s proportional hazards model. Small interfering RNA assay was used to explore the function of lncRNA Sox2ot on HCC cell migration and invasion. Results: lncRNA Sox2ot expression level was significantly higher in HCC tissues compared with adjacent non-tumor tissues (P<0.05). High expression of lncRNA Sox2ot was associated with histological grade, TNM stage, and vein invasion. The 5-year overall survival of high lncRNA Sox2ot expression group was significantly shorter than that of low lncRNA Sox2ot expression group (P<0.05). The multivariate Cox regression analysis indicated that lncRNA Sox2ot expression was an independent prognostic factor for overall survival. In addition, the metastasis ability of HCC cells was significantly decreased by knocking down lncRNA Sox2ot expression. Conclusions: The results suggested that lncRNA Sox2ot played crucial roles in promoting HCC cell migration and invasion, and might represent a novel prognostic biomarker for HCC.     

Impact of chemokine receptor CXCR3 on tumor-infiltrating lymphocyte recruitment associated with favorable prognosis in advanced gastric cancer

Chemokine receptor CXCR3 has been proved to play an important role in tumorigenesis and tumor progression in many malignancies, but its precise efficacy on gastric cancer (GC) has not been evaluated yet. The present study was aimed to explore the correlation of chemokine receptor CXCR3 with tumor-infiltrating lymphocytes (TILs) and prognosis in advanced gastric cancer (GC). Expression of CXCR3 and CD4+, CD8+ TILs was conducted in 192 advanced GC specimens and 48 corresponding paracancerous tissues by immunohistochemical (IHC) analysis. CXCR3 expression in GC tissues was significantly higher than that in paracancerous tissues (P<0.001) and CD8+, CD4+ TILs infiltration increased with high CXCR3 expression (P=0.032 and P<0.001, respectively). Our study showed significantly lower CXCR3 expression in patients with greater tumor invasion depth and lymph node metastasis compared with patients with lesser tumor invasion depth and without lymph node metastasis (P=0.002 and P=0.001, respectively). Univariate analysis indicated that patients with high CXCR3 expression and high CD8+ TILs infiltration had longer overall survival (OS) (log-rank test, P<0.001 and P=0.002, respectively). Univariate and multivariate analyses indicated that CXCR3 expression was an independent prognostic factor for OS (P=0.002). The present study suggested that CXCR3 expression was upregulated in advanced GC and was associated with increased CD4+, CD8+ TILs infiltration and improved OS. Therefore, CXCR3 overexpression is implicated as a favorable prognostic biomarker in human advanced GC.     

Correlation and prognostic significance of MMP-2 and TFPI-2 differential expression in pancreatic carcinoma

Aberrant expression of matrix metalloproteinase (MMP)-2 and tissue factor pathway inhibitor (TFPI)-2 not only correlate with tumorigenesis, but also with tumor invasion and metastasis. This study aims to investigate the correlation and prognostic significance of MMP-2 and TFPI-2 differential expression in pancreatic carcinoma. Immunohistochemistry was used to evaluate MMP-2 and TFPI-2 expression in tumor tissues and corresponding non-tumor tissues from 122 patients with pancreatic carcinoma. The results showed that the expression of MMP-2 was significantly (P < 0.05) higher in tumor tissues (78.7%) than in adjacent non-tumor tissues (27.9%), whereas the expression of TFPI-2 was significantly (P < 0.001) lower in tumor tissues (27.9%) than in adjacent non-tumor tissues (79.5%). Spearman’s rank correlation test showed a negative correlation between MMP-2 and TFPI-2 expression (r = -0.346, P < 0.001). Kaplan-Meier survival analysis showed that high MMP-2 expression was significantly correlated with decreased disease-free survival (DFS) (P < 0.001) and overall survival (OS) (P < 0.001), while high TFPI-2 expression was significantly associated with increased DFS (P < 0.001) and OS (P < 0.001) of the patients. Multivariate analysis showed that high MMP-2 expression can act as an independent predictive factor for poor DFS (P = 0.01); and low TFPI-2 expression as an independent prognostic factor for poor DFS (P < 0.001) and OS (P < 0.001). In conclusion, our findings suggested that the differential expression of MMP-2 and TFPI-2 have a negative correlation in pancreatic carcinoma tissues; they may be considered as valuable biomarkers for prognosis of pancreatic carcinoma.     

Overexpression of eIF3e is correlated with colon tumor development and poor prognosis

EIF3e is a component of the eukaryotic translation initiation factor 3 (eIF-3) complexes, which is an essential factor for initiation of protein synthesis in mammalian cells. Translational control plays key roles in the complex mechanism of cancer development and progression. However, the clinical significance of eIF3e in colon cancer remains to be elucidated. We analyzed the eIF3e expression in a tissue microarray (TMA), which contained 173 colon cancer tissues paired with adjacent normal mucosa and lymph node metastasis. The expression of eIF3e was significantly elevated in colon cancer tissues in comparison with those in adjacent normal mucosa (P < 0.001) and lymph node metastasis (P < 0.001). The high expression of eIF3e in colon cancer was significantly correlated with tumor size (P < 0.001), lymph node involvement (P < 0.001), distant metastasis (P < 0.001), clinical stage (P < 0.001), histopathologic classification (P < 0.001), and vessel invasion (P = 0.036). Univariate and multivariate analysis revealed that eIF3e is an independent prognosis factor for overall survival and disease-free survival in colon cancer. Down-regulation of eIF3e in vitro inhibited colon cancer cell proliferation, clonality and promoted cell apoptosis. Taken together, high eIF3e expression may contribute to tumor progression and predict poor prognosis in colon cancer.     

miR-21 inhibitor suppresses proliferation and migration of nasopharyngeal carcinoma cells through down-regulation of BCL2 expression

This study is to investigate the expression of miR-21 in nasopharyngeal carcinoma (NPC) cells, and the effect of miR-21 in the biological behavior and expression of B-cell lymphoma 2 (BCL2) in NPC cells. Paired NPC and adjacent non-tumor tissues were obtained from 53 patients who underwent primary surgical resection of NPC tissues. Luciferase reporter assay was performed to test whether BCL2 is a direct target of miR-21. Methylthiazolyl blue tetrazolium assay and colony assay were used to evaluate the effect of miR-21 on NPC cell proliferation. Transwell and wound-healing assays were carried out to test the effect of low expression of miR-21 on cancer cell migration and invasion. QRT-PCR and Western blotting were used to measure the levels of mRNA and protein expression, respectively. Tumor tissues showed a positive correlation between the levels of miR-21 and BCL2 protein expression. Cells transfected with miR-21 inhibitor healed slower compared the control (P < 0.05). In addition, cell migration was notably inhibited by the down-regulation of miR-21 in vitro (P < 0.05). The reduction in miR-21 expression showed a remarkable effect on the biological behavior of NPC cell clone formation (P < 0.05). Low expression of miR-21 by transfection with miRNA expression plasmid led to a decrease in BCL2 expression, which was accompanied by reduced migration and proliferation of the cancer cells. Our results demonstrated that miR-21 inhibitor down-regulated BCL2 expression level, suggesting that BCL2 might be a target gene for the initiation and development of NPC cells.     

Potential role of CXCR3 in proliferation and invasion of prostate cancer cells

Aim: To investigate the potential role of CXCR3 expression on prostate cancer cell proliferation and invasion and to illustrate its mechanism. Methods: Human PC-3 cells were transfected with siRNA-CXCR3A and siRNA-CXCR3B plasmids respectively. The mRNA expressions of CXCR3A and CXCR3B in PC-3 cells from each group were analyzed using RT-PCR. Besides, cell proliferation ability and cell invasion ability of PC-3 cells in each group were analyzed using MTT assay and Matrige assay respectively. Additionally, expressions of CXCR3 downstream proteins were detected using Western blotting. Results: mRNA level of CXCR3A was decreased while CXCR3B mRNA level was increased in PC-3 cells (P<0.05). Compared with the controls, down-regulation of CXCR3A but up-regulation of CXCR3B significantly inhibited PC-3 cell proliferation and cell invasion ability (P<0.05). Besides, aberrant CXCR3 expression significantly increased expressions of phospholipase C (PLCβ), matrix metallo proteinase (MMP-1), and MMP-3 except MMP-7 in PC-3 cells (P<0.05). Conclusion: The data presented in our study suggested that aberrant CXCR3 expression may play crucial roles in suppressing PC metastasis via inhibiting cell proliferation and invasion ability through the PCLβ signaling pathway.     

Expression of PBK/TOPK in cervical cancer and cervical intraepithelial neoplasia

objectives: To evaluate the expression of PBK/TOPK (PDZ-binding kinase/T-LAK cell-originated protein kinase) and its clinical significance in cervical cancer and cervical intraepithelial neoplasia. Methods: PBK/TOPK expression was detected in 28 cases of low-grade cervical intraepithelial neoplasia (CINI), 62 cases of high-grade intraepithelial neoplasia and 80 cases of cervical cancer by immunohistochemistry (IHC). Then, the correlation between PBK/TOPK expression and clinicopathological features was quantitatively analyzed by measuring the positive unit (PU). Results: PBK/TOPK expression was significantly greater in cervical cancer than that in high-grade intraepithelial neoplasia and CINI (P < 0.05). Meanwhile, PBK/TOPK expression in high-grade intraepithelial neoplasia was significantly higher compared with that in CINI (P < 0.05). In addition, PBK/TOPK expression in cervical cancer significantly correlated with histological type, differentiation, lymph node metastasis, vaginal and cervical invasion, TNM stage and tumor size (P < 0.05). Conclusion: PBK/TOPK expression is closely associated with cervical cancer and cervical intraepithelial neoplasia, which may be served as a useful target for tumor diagnosis and immunotherapy.     

Decreased expression of SEMA3A is associated with poor prognosis in gastric carcinoma

Background/purpose: SEMA3A (semaphorin-3A), is a secreted protein that belongs to the semaphorin family and can function as both a chemoattractive agent or a chemorepulsive agent. SEMA3A has been shown to be a tumor suppressor in various cancers. This study investigated the expression of SEMA3A in gastric cancer and its prognostic value for gastric cancer patients. Methods: We examined the expression of SEMA3A in paired cancerous and matched adjacent noncancerous gastric mucosa tissues by real-time quantitative RT-PCR (qRT-PCR) and western blotting. In vitro, we evaluate the effects of SEMA3A on gastric cancer cell proliferation and migration by MTT, transwell and wound-healing assays. Furthermore, we analyzed SEMA3A expression in 128 patients who underwent resection procedures using immunohistochemistry. The relationships between the SEMA3A expression levels, the clinicopathological factors, and patient survival were investigated. Results: Our results revealed decreased SEMA3A mRNA (P = 0.0037) and protein (P = 0.033) expression in tumor tissue samples compared with matched adjacent non-tumorous tissue samples. Overexpression of SEMA3A inhibits gastric cancer cell proliferation and migration in vitro. Immunohistochemical staining data showed that SEMA3A expression was significantly decreased in 54.68% of gastric cancer cases. In addition, the chi-square test revealed that low SEMA3A expression was significantly correlated with poor differentiation (P = 0.015), Vascular invasion (P = 0.001), depth of invasion (P < 0.001), lymph node metastasis (P = 0.029), distant metastasis (P = 0.002) and advanced TNM stage (P = 0.003). SEMA3A expression was positively correlated with clinical TNM stage, that suggested the more advanced clinical TNM stage corresponding to the lower expression level of SEMA3A (r_s = -0.322, P < 0.001) by Spearman rank correlation analysis. Kaplan-Meier survival analysis demonstrated that low expression of SEMA3A was significantly correlated with a poor prognosis for gastric cancer patients (P < 0.001). The multivariate analysis revealed that SEMA3A expression was an independent prognostic factor of the overall survival rate of patients with gastric cancer. Conclusion: SEMA3A expression decreased significantly as gastric cancer progressed and metastasized, suggesting that SEMA3A might serve as a candidate tumor suppressor and a potential prognostic biomarker in gastric carcinogenesis.