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1.
Introduction: miR-32 has recently been found to be implicated in many critical processes in various types of human cancer. However, its clinical significance in human non-small cell lung cancer (NSCLC) has not yet been elucidated. In the present study, we investigated the expression of miR-32 in NSCLC and analyzed its association with clinical features and prognosis of NSCLC patients. Methods: Quantitative real-time PCR (qRT-PCR) was used to measure expression level of miR-32 in lung cancer cell lines, normal bronchial epithelial cells, 90 pairs of tumor samples and adjacent non-tumor tissues. To determine its prognostic value, overall survival was evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were performed using the Cox proportional hazard analysis. Results: The expression of miR-32 was significantly decreased in lung cancer cell lines and NSCLC tissues compared with normal bronchial epithelial cells and adjacent non-tumor tissues (P < 0.05). This reduction of miR-32 was associated with tumor stage and lymph node metastasis (P < 0.05). Moreover, Kaplan-Meier analysis demonstrated that patients with low miR-32 expression had shorter overall survival time than those with high miR-32 expression (P < 0.05). Univariate analysis revealed statistically significant correlations between overall survival and miR-32 level, tumor stage and lymph node metastasis (P < 0.05). Furthermore, miR-32 levels, tumor stage and lymph node metastasis were independently associated with overall survival (P < 0.05). Conclusions: Our results provided the first evidence that down-regulation of miR-32 was correlated with NSCLC progression, and miR-32 might be a potential molecular biomarker for predicting the prognosis of patients.  相似文献   

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Objectives: The aim was to evaluate the clinical significance and prognostic value of tissue miR-150 expression in non-small cell lung cancer (NSCLC) patients. Materials and methods: Quantitative real-time PCR was used to analyze the expression of miR-150. Overall survival (OS) was estimated using the Kaplan-Meier method, and the differences in survival were compared using the log-rank test. A Cox proportional hazards model was used for multivariate analysis. Results: Mean miR-150 levels were significantly higher in NSCLC tissues compared with matched non-cancerous tissues (4.07 ± 2.33 vs. 1.00 ± 0.46, P < 0.0001). The level of miR-150 in NSCLC was strongly correlated with lymph node metastasis (P = 0.04), distant metastasis (P = 0.01) and clinical TNM stage (P = 0.02). Kaplan-Meier analysis showed that the cumulative 5-year OS rate was 40.8% in the high expression group, and 69.2% in the low expression group. The log-rank test showed that the OS rate of patients with high miR-150 expression was significantly poorer than that of the remaining cases (P = 0.007). Conclusion: Our data indicated that overexpression of miR-150 in NSCLC tissues has prognostic value.  相似文献   

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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.  相似文献   

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Background: miR-153 has been found to be significantly decreased in non-small cell lung cancer (NSCLC) tissues; however, its clinical significance has not been investigated. Methods: The expression patterns of miR-153 in 137 pairs of human lung cancer tissues and adjacent normal lung tissues were analyzed using qRT-PCR. The relationships between miR-153 expression and clinicopathological parameters were examined by chi-square test. Kaplan-Meier method and the log-rank test were used to determine the difference in overall survival (OS) rates between two groups. Results: The expression of miR-153 was reduced significantly, compared with adjacent normal lung tissues (P<0.05). We observed that the expression level of miR-153 was positively correlated with the clinical stage (P=0.005), lymph node status (P=0.014), distant metastasis (P=0.004), and differentiated degree (P<0.001) in NSCLC patients. According to the Kaplan-Meier survival analysis, the patients with low miR-153 expression exhibited evidently poorer overall survival rates than those with high miR-153 expression (P=0.003). Multivariate analysis showed that the expression of miR-153 was an independent and significant factor associated with poor OS rates (P=0.002). Conclusion: Decreased expression of miR-153 might be a potential unfavorable prognostic factor for patients with NSCLC, and further studies would be needed to prove our findings.  相似文献   

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Objective: MiRNAs play crucial roles in progression of cancer. However, the underlying mechanisms of miRNAs in non small cell lung cancer are still poorly understood. The aim of this study was to investigate the expression level of microRNA-126 (miR-126) and microRNA-133b (miR-133b) and also their association with clinicopathological features in patients with non small cell lung cancer (NSCLC). Methods: Total RNA was purified from NSCLC tissues and adjacent non-tumor tissues and then quantitative real-time PCR (qRT-PCR) was used to evaluate the expression rate of microRNAs. Furthermore, the association of miR-126 and miR-133b level with clinicopathological features and prognosis were evaluated. Results: Our findings showed that expression of miR-126 was decreased in NSCLC tissues compared with adjacent non-tumor tissues. On the other hand, a lower expression of miR-133b was seen in NSCLC tissues when compared with adjacent non-tumor tissues. In term of miR-126, our results showed that miR-126 was associated with tumor stage and lymph nodes metastasis (P<0.05). In term of miR-133b, our finding indicated that decreased expression of miR-133b was correlated with advanced tumor stage and lymph nodes metastasis (P<0.05). Kaplan-Meier analysis and log-rank test indicated that patients with low expression of miR-126 and miR-133b had a shorter overall survival (log-rank test; P<0.05). Multivariate Cox proportional hazards model revealed that low expression of miR-126 and miR-133b, advanced tumor stage and lymph nodes metastasis were independent prognostic factors for overall survival of NSCLC patients. Conclusions: These findings suggested that miR-126 and miR-133b might play a key role in the progression and metastasis of NSCLC and would be applied as a novel therapeutic agent.  相似文献   

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Background: The aim of this study was to clarify the clinicopathological significance of miRNA-148b (miR-148b) expression in NSCLC, and to explore the correlation between miR-148b level and the prognosis of patients with NSCLC. Methods: 151 patients diagnosed with NSCLC between May 2007 and April 2012 were included in the present study. Real-time RT-PCR method was used to assess the expression levels of miR-148b. The differences between two groups were assessed using Student’s t -test, and the Kaplan-Meier method was used to estimate overall survival. Results: The expression of miR-148b was decreased in tumor tissues compared to corresponding adjacent normal lung tissues (0.37 ± 0.12 vs. 1.00 ± 0.53, P < 0.05). Low miR-148b expression was significantly associated with TNM stage (P = 0.014), lymph node metastasis (P = 0.031), and distant metastasis (P = 0.008). Kaplan-Meier survival analysis showed that patients with low expression of miR-148b had significantly worse overall survival rates compared with those who had cancers with high miR-148b expression (log-rank test P = 0.039). Furthermore, multivariate Cox proportional hazards model analysis showed that miR-148b expression was independently associated with overall survival of patients with NSCLC (HR = 2.357, 95% CI: 1.612-9.212, P = 0.011). Conclusion: our data indicate that decreased expression of miR-148b in NSCLC tissues has prognostic value.  相似文献   

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Non-small lung cell carcinoma (NSCLC) is a leading lethal disease and a global health burden. The function of the Sex determining region Y (SRY)-related high mobility group box (SOX) family gene in cancer has attracted the attention of more and more scientists recently, yet there are few reports regarding the role of SOX in NSCLC. Our study aimed to investigate the expression of SOX8, a protein belonging to the E group of the SOX family, as well as SOX9, in non-small cell lung cancer (NSCLC) and the relationship of gene expression to clinicopathological factors and prognosis in patients. Immunohistochemical analysis was used to measure the expression of SOX8 in 80 NSCLC and 7 adjacent normal tissues. SOX8 expression was detected as elevated in tumor samples and correlated to tumor size (P < 0.001), lymph node metastasis (P = 0.001), differentiation classification (P = 0.015), and clinical stage (P = 0.013) significantly. Moreover, Kaplan-Meier survival analysis demonstrated that shorter survival time for patients who had higher SOX8 expression (P < 0.001). In addition, our experiments indicate that miRNA-124 functions as a tumor suppressor in NSCLC. We also demonstrate miRNA-124 directly targeted and decreased SOX8 in NSCLC cell lines, suggesting smiRNA-124 may regulate NSCLC cell proliferation via decreasing SOX8 (oncogenicity of biomarker in NSCLC).  相似文献   

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Non-small lung cell carcinoma (NSCLC) is a leading lethal disease and a global health burden. The function of the Sex determining region Y (SRY)-related high mobility group box (SOX) family gene in cancer has attracted the attention of more and more scientists recently, yet there are few reports regarding the role of SOX in NSCLC. Our study aimed to investigate the expression of SOX8, a protein belonging to the E group of the SOX family, as well as SOX9, in non-small cell lung cancer (NSCLC) and the relationship of gene expression to clinicopathological factors and prognosis in patients. Immunohistochemical analysis was used to measure the expression of SOX8 in 80 NSCLC and 7 adjacent normal tissues. SOX8 expression was detected as elevated in tumor samples and correlated to tumor size (P < 0.001), lymph node metastasis (P = 0.001), differentiation classification (P = 0.015), and clinical stage (P = 0.013) significantly. Moreover, Kaplan-Meier survival analysis demonstrated that shorter survival time for patients who had higher SOX8 expression (P < 0.001). In addition, our experiments indicate that miRNA-124 functions as a tumor suppressor in NSCLC. We also demonstrate miRNA-124 directly targeted and decreased SOX8 in NSCLC cell lines, suggesting smiRNA-124 may regulate NSCLC cell proliferation via decreasing SOX8 (oncogenicity of biomarker in NSCLC).  相似文献   

10.
Objective: We aimed to explore what impact miR-503 has on the prognosis of patients with non-small cell lung cancer (NSCLC). Methods: Cancer and matched non-malignant lung tissue specimens were collected from 109 patients who underwent surgery in Tanisha Hospital from Jun 2006 to July 2013. Overall survival (OS) curves were analyzed using the Lapland-Meier method, and the differences were examined using log-rank tests. Cox proportional- hazards regression analysis was applied in order to estimate univariate and multivariate hazard ratios for OS. Results: The relative expression of miR-503 in NSCLC tissues (0.366 ± 0.130) was significantly lower than that in matched noncancerous lung tissues (1.667 ± 1.047, P < 0.01). Statistically significant association was observed between miR-503 expression and lymphatic invasion (P = 0.005), distant metastasis (P = 0.002), TNM stage (P = 0.008), and tumor grade (P = 0.043). Lapland Meier analysis clearly illustrated that the patients with the lower expression of miR-503 had a worse outcome compared to patients with higher miR-503 expression (P = 0.004). Furthermore, multivariate analysis revealed that miR-503 expression level was an independent prognostic factor for overall survival (HR = 3.992, 95% CI: 2.276-9.872; P = 0.018) in NSCLC. Conclusion: In patients with NSCLC, low miR-503 expression is an independent prognostic factor.  相似文献   

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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 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.  相似文献   

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Tumor-stroma ratio (TSR) has been identified as a new and practicable prognostic factor in some solid tumors. The aim of the study is to evaluate the prognostic value of TSR in non-small cell lung cancer (NSCLC). A total of 404 patients who underwent surgery resection for NSCLC were included in this study. TSR was assessed visually on the hematoxylin-stained tissue sections of surgical specimens. Patients with more than 50% intratumor stroma were quantified as the stroma-rich group and those with less than 50% as the stroma-poor group. In 404 cases of tissue samples, 302 cases were included in the stroma-poor group, while 102 cases in stroma-rich group. The different expression of TSR in NSCLC tissue was not correlated with gender, age, smoking history, tumor diameter, histology, differentiation grade and pTNM staging. In the Cox univariate and multivariate analyses of the 5-year OS, the HRs of the TSR were 1.818 (95% CI; 1.323-2.497; P<0.001) and 1.748 (95% CI; 1.262-2.422; P<0.05), respectively. As for DFS, the HRs were 1.715 (95% CI; 1.249-2.354; P<0.001) and 1.570 (95% CI; 1.135-2.172; P<0.05). Stroma-rich tumors were associated with poor prognosis and an increased risk of relapse, which may serve as a new prognostic histological characteristic in NSCLC.  相似文献   

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To investigate the expression of homeobox B (Hoxb)-13 and analyze its relationship with tumor angiogenesis, epithelial-mesenchymal transition (EMT)-associated markers (E-cadherin and vimentin), clinicopathologic data and prognosis in pancreatic carcinoma. Immunohistochemistry was applied to determine the level of Hoxb-13 expression in tumor tissues and surrounding non-tumor tissues from 85 subjects with pancreatic carcinoma. Besides, vascular endothelial growth factor (VEGF), CD31, E-cadherin and vimentin were also detected in tumor tissues by immunostaining. We found that the level of Hoxb-13 expression was significantly higher in pancreatic carcinoma tissues than in paracarcinomatous tissues (P < 0.05). Hoxb-13 staining was positively correlated with VEGF (r = 0.429, P < 0.001) and microvessel density (MVD) (r = 0.454, P < 0.001). Likewise, Hoxb-13 staining was positively correlated with vimentin (r = 0.448, P < 0.001); while it was negatively correlated with E-cadherin (r = -0.405, P < 0.001). High Hoxb-13 expression was associated with aggressive clinicopathological characteristics, worse disease-free survival (DFS) (P < 0.001) and worse overall survival (OS) (P < 0.001). Multivariate analysis showed that Hoxb-13 was an independent predictor for poor DFS (P < 0.001) and OS (P = 0.002). In conclusion, our data show that overexpressed Hoxb-13 is correlated with tumor angiogenesis, aberrant expression of EMT-associated markers and aggressive clinicopathological characteristics, and serves as a promising marker for unfavourable prognosis in pancreatic carcinoma.  相似文献   

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Despite advances made in the diagnosis and treatment of human colorectal cancer (CRC), the long-term survival for CRC remains poor. Long non-coding RNA anti-differentiation ncRNA (lncRNA DANCR) was identified to be involved in carcinogenesis of hepatocellular carcinoma. While its expression in CRC and potential role in tumor progression is still unknown. In the present study, we investigated the expression level of lncRNA DANCR as well as its association with CRC progression and prognosis. The expression of lncRNA DANCR was detected by quantitative real-time PCR (qRT-PCR) in 104 CRC specimens. The prognostic value of lncRNA DANCR was further analysis. Our results showed that lncRNA DANCR expression was increased in CRC tissues compared with that in adjacent normal tissues (P<0.05). In addition, tumors with high lncRNA DANCR expression was correlated with TNM stage, histologic grade, and lymph node metastasis (P<0.05). Kaplan-Meier analysis showed that patients with high lncRNA DANCR expression had a shorter overall survival (OS) and disease-free survival (DFS) compared with the low lncRNA DANCR expression group (P<0.05). Moreover, in a multivariate Cox model, our results showed that lncRNA DANCR expression was an independent poor prognostic factor for both OS and DFS in CRC. Our data indicated that lncRNA DANCR expression might be a novel potential biomarker for CRC prognosis.  相似文献   

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Phosphatase and tensin homolog deleted on chromosome 10(PTEN) and the proliferating antigen Ki67 have been widely studied in several tumors.However,their role as indicator in non-small cell lung cancer(NSCLC)remains unknown.Here,we investigated the expression of PTEN and Ki67 in NSCLC tissues and paired normal lung tissues to identify whether these proteins are associated with lung cancer development and survival.Immunohistochemistry for PTEN and Ki67 was performed on 67 lung cancer tissues and 41 paired adjacent normal lung tissues to detect the expression of these two proteins.The expression of PTEN in NSCLC tissues(32.8%) was significantly lower than that in normal tissues(82.9%,P 〈 0.05).In contrast,the expression of Ki67 in NSCLC tissues(76.1%) was significantly higher than that in normal tissues(27.3%,P 〈 0.05).Expression of both PTEN and Ki67 were strongly associated with tumor histology,clinical stage,lymph node metastasis,differentiation and4-year postoperative survival rate(P 〈 0.05).However,PTEN expression was negatively correlated with Ki67 expression(r =-0.279,P 〈 0.05).In conclusion,low PTEN expression and Ki67 overexpression are associated with malignant invasion and lymph node metastasis of NSCLC.These proteins may serve as diagnostic and prognostic biomarkers of NSCLC.  相似文献   

18.
Previous studies have shown that chemokine receptor CXCR7 plays critical roles in tumor development. However, the clinicopathological and prognositic significance of CXCR7 in colorectal carcinoma (CRC) has not been fully understood. The aim of our study is to investigate the expression of CXCR7 and its clinical significance in CRC. First, quantitative RT-PCR and Western blot assays were performed to determine the expression of CXCR7 mRNA and protein in 20 paired of CRC tissues and corresponding adjacent non-tumor tissues. Next, immunohistochemistry was performed to detect the expression of CXCR7 protein in another 96 cases of CRC tissues, and analyze its correlation with clinicopathological factors of patients. Finally, the correlation of CXCR7 with 5-year overall survival (OS) and progression free survival (PFS) was statistically analyzed by the Kaplan-Meier method and Cox proportional hazards model. Results showed that the expression levels of CXCR7 mRNA and protein were significantly higher in CRC tissues than in normal tissues. Positive CXCR7 expression was observed to be significantly correlated with lymph nodal metastasis (P < 0.001), distant metastasis (P = 0.017), and advanced TNM stage (P < 0.001). Patients with positive expression of CXCR7 were demonstrated to be associated with worse OS and PFS (P < 0.001, P < 0.001, respectively). Moreover, multivariate survival analysis revealed that CXCR7 expression level might be an independent predictive factor for OS and PFS of CRC patients. Collectively, positive CXCR7 expression in CRC was correlated with tumor development and poor prognosis of patients.  相似文献   

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Background and purpose: To investigate the clinical significance of microRNA (miR)-23a and miR-23b expression in human gastric cancer (GC). Methods: Quantitative RT-PCR was performed to detect the expression changes of miR-23a and miR-23b in 160 human GC tissues and paired normal mucosa. The associations between miR-23a and miR-23b expression, and the selected clinicopathological characteristics and patients’ prognosis were also evaluated. Results: MiR-23a (GC vs. Normal: 3.98 ± 1.23 vs. 2.29 ± 1.12, P < 0.001) and miR-23b (GC vs. Normal: 3.70 ± 1.24 vs. 1.58 ± 1.18, P < 0.001) expression were both increased dramatically when compared with paired normal mucosa. Notably, the expression levels of miR-23a in GC tissues were positively correlated with those of miR-23b (Spearman correlation coefficient r = 0.77, P < 0.001). Then, the coexpression of miR-23a and miR-23b (miR-23a-high/miR-23b-high) in GC tissues was significantly associated with the advanced TNM stage (P < 0.001), the presence of lymph node metastasis (P = 0.008) and the great depth of invasion (P = 0.02). Furthermore, both univariate and multivariate analyses showed that miR-23a/miR-23b co-expression was an independent predictor for unfavorable overall survival. Conclusions: These results suggest that the dysregulation of miR-23a and miR-23b may be implicated in the progression of human GC. Combined expression of miR-23a and miR-23b appears to be a valuable marker for prognosis of this disease.  相似文献   

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Golgi phosphoprotein3 (GOLPH3) is known as an oncoprotein and may be a prognostic biomarker in various tumors. Here we performed a meta-analysis on the association of GOLPH3 expression and survival in solid tumors. All eligible studies were identified in Embase, PubMed and Web of Science Databases up to November 2014. Data about overall survival (OS), and disease-free survival (DFS) were extracted and pooled hazard ratios (HRs) of GOLPH3 for survival were calculated by using a random-effect model. Heterogeneity and publication bias were also assessed. A total of 15 eligible studies which comprised of 2529 cases were included in this global analysis: 14 were dealing with overall survival (OS) and 6 were with disease-free survival (DFS). We found that GOLPH3 overexpression was associated with shorter OS (HR 2.487, 95% CI 1.897-3.258, P < 0.001) and DFS (HR 1.911, 95% CI 1.245-2.932, P = 0.003) in general carcinomas. Importantly, subgroup analysis suggested that overexpression of GOLPH3 correlated with shorter OS in urogenital system cancers (HR 4.258, 95% CI 1.81-4.91, P < 0.001). Moreover, publication bias was not significant (P > 0.05). In conclusion, the present meta-analysis showed that overexpression of GOLPH3 predicts poor prognosis in solid tumors.  相似文献   

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