Amplifications of NCOA3 gene in colorectal cancers in a Chinese population

AIM: To investigate the copy number variation of NACO3 gene in colorectal cancer (CRC) and its correlation with tumor progression. METHODS: A total of 142 samples of case-matched CRC tissues and adjacent normal tissues were obtained from patients undergoing bowel resection. Quantitative real-time polymerase chain reaction method was used to investigate the copy number variations of NCOA3 as well as gene expression in the collected tissues. RESULTS: Copy number gains of NCOA3 were detected in 39 CRC samples (27.5%) and were correlatedwith tumor progression (χ2 = 6.42, P = 0.0112). Moreover, there was a positive correlation between copy number gain and mRNA over-expression of NCOA3 in CRCs (P = 0.0023). Expression level of NCOA3 mRNA was also enhanced in the CRC samples with unaltered copy numbers (3.85 ± 1.23 vs 2.71 ± 0.64, P 0.01). CONCLUSION: Sporadic colorectal cancers exhibit different mechanisms of NCOA3 regulation.     

miR-422a is an independent prognostic factor and functions as a potential tumor suppressor in colorectal cancer

AIM: To determine the expression of miR-422a in colorectal cancer (CRC) tissues and to further explore the prognostic value and function of miR-422a in CRC carcinogenesis.METHODS: miR-422a expression was analyzed in 102 CRC tissues and paired normal mucosa adjacent to carcinoma by quantitative real-time PCR. The relationship of miR-422a expression with clinicopathological parameters was also analyzed. Kaplan-Meier analysis and Cox multivariate analysis were performed to estimate the potential role of miR-422a. Cell proliferation, migration, and invasion were used for in vitro functional analysis of miR-422a.RESULTS: The levels of miR-422a were dramatically reduced in CRC tissues compared with normal mucosa (P < 0.05), and significantly correlated with local invasion (P = 0.004) and lymph node metastasis (P < 0.001). Kaplan-Meier survival and Cox regression multivariate analyses revealed that miR-422a expression (HR = 0.568, P = 0.015) and clinical TNM stage (HR = 2.942, P = 0.003) were independent prognostic factors for overall survival in CRC patients. Furthermore, in vitro experiments showed that overexpression of miR-422a inhibited the proliferation, migration, and invasion of SW480 and HT-29 cells.CONCLUSION: Down-regulation of miR-422a may serve as an independent prognosis factor in CRC. MiR-422a functions as a tumor suppressor and regulates progression of CRC.     

Insulin-like growth factor-1 induces lymphangiogenesis and facilitates lymphatic metastasis in colorectal cancer

AIM:To investigate the expression of insulin-like growth factor-1(IGF-1)/insulin-like growth factor-1 receptor(IGF-1R)in colorectal cancer(CRC)tissues and to analyze their correlation with lymphangiogenesis and lymphatic metastasis.METHODS:Immunohistochemistry was used to evaluate IGF-1 and IGF-1R expression and lymphatic vessel density(LVD)in 40 CRC specimens.The correlation between IGF-1/IGF-1R and LVD was investigated.Effects of IGF-1 on migration and invasion of CRC cells were examined using transwell chamber assays.A LoVo cell xenograft model was established to further detect the role of IGF-1 in CRC lymphangiogenesis in vivo. RESULTS:Elevated IGF-1 and IGF-1R expression in CRC tissues was correlated with lymph node metastasis(r=0.715 and 0.569,respectively,P<0.05)and tumor TNM stage(r=0.731 and 0.609,P<0.05).A higher LVD was also found in CRC tissues and was correlated with lymphatic metastasis(r=0.405,P<0.05).A positive correlation was found between LVD and IGF-1R expression(r=0.437,P<0.05).Transwell assays revealed that IGF-1 increased the migration and invasion of CRC cells.In vivo mouse studies showed that IGF-1 also increased LVD in LoVo cell xenografts.CONCLUSION:IGF-1/IGF-1R signaling induces tumorassociated lymphangiogenesis and contributes to lymphatic metastasis of CRC.     

MT1M and MT1G promoter methylation as biomarkers for hepatocellular carcinoma

AIM:To investigate the potential of promoter methylation of two tumor suppressor genes(TSGs)as biomarkers for hepatocellular carcinoma(HCC).METHODS:A total of 189 subjects were included in this retrospective cohort,which contained 121 HCC patients without any history of curative treatment,37 patients with chronic hepatitis B(CHB),and 31 normal controls(NCs).DNA samples were extracted from 400μL of serum of each subject and then modified using bisulfite treatment.Methylation of the promoters of the TSGs(metallothionein1M,MT1M;and metallothionein 1G,MT1G)was determined using methylation-specific polymerase chain reaction.The diagnostic value of combined MT1M and MT1G promoter methylation was evaluated using the area under the receiver operating characteristic curves.RESULTS:Our results indicated that the methylation status of serum MT1M(48.8%,59/121)and MT1G(70.2%,85/121)promoters in the HCC group was significantly higher than that in the CHB group(MT1M 5.4%,2/37,P<0.001;MT1G 16.2%,6/37,P<0.001)and NC group(MT1M 6.5%,2/31,P<0.001;MT1G 12.9%,4/27,P<0.001).Aberrant serum MT1M promoter methylation gave higher specificity to discriminate HCC from CHB(94.6%)and NCs(93.5%),whereas combined methylation of serum MT1M and MT1G promoters showed higher diagnostic sensitivity(90.9%),suggesting that they are potential markers for noninvasive detection of HCC.Furthermore,MT1M promoter methylation was positively correlated with tumor size(rs=0.321,P<0.001),and HCC patients with both MT1M and MT1G promoter methylation tended to show a higher incidence of vascular invasion or metastasis(P=0.018).CONCLUSION:MT1M and MT1G promoter methylation may be used as serum biomarkers for noninvasive detection of HCC.     

Association of Fusobacterium nucleatum infection with colorectal cancer in Chinese patients

AIM: To investigate Fusobacterium nucleatum(F. nucleatum) abundance in colorectal cancer(CRC) tissues and its association with CRC invasiveness in Chinese patients.METHODS: The resected cancer and adjacent normal tissues(10 cm beyond cancer margins) from 101 consecutive patients with CRC were collected. Fluorescent quantitative polymerase chain reaction(FQ-PCR) was applied to detect F. nucleatum in CRC and normal tissues. The difference of F. nucleatum abundance between cancer and normal tissues and the relationship of F. nucleatum abundance with clinical variables were evaluated. Fluorescence in situ hybridization(FISH) analysis was performed on 22 CRC tissues with the highest F. nucleatum abundance by FQ-PCR testing to confirm FQ-PCR results.RESULTS: The median abundance of F. nucleatum in CRC tissues [0.242(0.178-0.276)] was significantly higher than that in normal controls [0.050(0.023-0.067)](P 0.001). F. nucleatum was over-represented in 88/101(87.1%) CRC samples. The abundance of F. nucleatum determined by 2~(-ΔCT) was significantly greater in tumor samples [0.242(0.178, 0.276)] than in normal controls [0.050(0.023, 0.067)](P 0.001). The frequency of patients with lymph node metastases was higher in the over-abundance group [52/88(59.1%)] than in the under-abundance group [0/13(0%)](P 0.005). No significant association of F. nucleatum with other clinico-pathological variables was observed(P 0.05). FISH analysis also found more F. nucleatum in CRC than in normal tissues(median number 6, 25~(th) 3, 75~(th) 10 vs 2, 25~(th) 1, 75~(th) 5)(P 0.01).CONCLUSION: F. nucleatum was enriched in CRC tissues and associated with CRC development and metastasis.     

miR-132 inhibits colorectal cancer invasion and metastasis via directly targeting ZEB2

AIM:To investigate the biological role and underlying mechanism of miR-132 in colorectal cancer(CRC)progression and invasion.METHODS:Quantitative RT-PCR analysis was used to examine the expression levels of miR-132 in five CRC cell lines(SW480,SW620,HCT116,HT29 and LoVo)and a normal colonic cell line NCM460,as well as in tumor tissues with or without metastases.The KaplanMeier method was used to analyze the prognostic significance of miR-132 in CRC patients.The biological effects of miR-132 were assessed in CRC cell lines using the transwell assay.Quantitative RT-PCR and western blot analyses were employed to evaluate the expression of miR-132 targets.The regulation of ZEB2 by miR-132was confirmed using the luciferase activity assay.RESULTS:miR-132 was significantly down-regulated in the CRC cell lines compared with the normal colonic cell line(P<0.05),as well as in the CRC tissues withdistant metastases compared with the tissues without metastases(10.52±4.69 vs 23.11±7.84)(P<0.001).Down-regulation of miR-132 was associated with tumor size(P=0.016),distant metastasis(P=0.002),and TNM stage(P=0.020)in CRC patients.Kaplan-Meier survival curve analysis indicated that patients with low expression of miR-132 tended to have worse diseasefree survival than patients with high expression of miR-132(P<0.001).Moreover,ectopic expression of miR-132 markedly inhibited cell invasion(P<0.05)and the epithelial-mesenchymal transition(EMT)in CRC cell lines.Further investigation revealed ZEB2,an EMT regulator,was a downstream target of miR-132.CONCLUSION:Our study indicated that miR-132 plays an important role in the invasion and metastasis of CRC.     

Hypermethylation of TGF-β1 gene promoter in gastric cancer

AIM:To examine transforming growth factor-β1(TGF-β1)promoter methylation in gastric cancer and to determine if Helicobacter pylori(H.pylori)or interleukin(IL)-1β could induce TGF-β1 hypermethylation in vitro.METHODS:We examined the frequency and extent of TGF-β1 promoter methylation using methylationspecific PCR in the gastric tissues from 47 gastric cancer patients and 39 non-gastric cancer subjects.H.pylori infection was confirmed by a positive result from either a serological test,histological analysis or C13urea breath test.GES-1 and MKN-45 cells co-cultured with H.pylori or treated with IL-1β for 12,24 and 48 h in vitro tested the effects of H.pylori or IL-1β on TGF-1β.RESULTS:Twenty-four/forty-seven(51%)cases of gastric cancer(GC)tissues showed TGF-β1 promoter methylation,15/47(31.9%)cases of matched noncancerous gastric mucosa tissues from the GC patients,and 11/39(28%)case of the normal gastric mucosa tissues from non-GC subjects showed TGF-β1 promoter methylation(51%vs 28%,P<0.05).Significantly higher levels of methylation of TGF-β1 were found in the tumor tissues than in non-tumor tissues from GC patients(0.24±0.06 vs 0.17±0.04,P<0.05)and normal gastric tissues from non-GC subjects(0.24±0.06 vs 0.15±0.03,P<0.05).TGF-β1 methylation was found in 48.3% of H.pylori-positive gastric mucosal tissues whereas only 23.1% of H.pylori-negative gastric mucosal tissues showed TGF-β1 methylation(48.3%vs 23.1%,P<0.05).IL-1β appeared to induce a dose-dependent methylation of TGF-β1 and the strongest methylation was observed in GES-1 cells treated with 2.5 ng/mL of IL-1β for 48 h.Further studies showed that pre-treatment of GES-1 cells with 20ng/mL IL-1RA for 1 h could partially abolish the effect of IL-1β on TGF-β1 methylation.Infection of GES-1cells by H.pylori was not found to induce significant TGF-β1 promoter methylation.CONCLUSION:Our data revealed that TGF-1 promoter is methylated in GC patients.IL-1β may be an important mediator for H.pylori induced gene methylation during GC     

Fibulin-1 Is Downregulated Through Promoter Hypermethylation in Colorectal Cancer: A Consort Study

Fibulin-1 (FBLN1) is involved in the progression of some types of cancer. However, the role of FBLN1 in colorectal cancer (CRC) has not been examined. The purpose of this study was to understand the molecular mechanisms and clinical significance of FBLN1 inactivation in CRC.The expression of FBLN1 in CRC tissues and adjacent normal tissues was analyzed by immunohistochemical analysis and quantitative real-time polymerase chain reaction (qRT-PCR). Methylation-specific polymerase chain reaction (MSP) and bisulfite sequencing PCR (BSP) were performed to examine the methylation status of the FBLN1 gene promoter. Furthermore, the methylated level of FBLN1 was analyzed with the clinicopathological characteristics.Immunohistochemical analysis and qRT-PCR analysis showed that FBLN1 protein and messenger RNA (mRNA) levels in tumor tissues were both significantly decreased compared with that in adjacent nontumor tissues. The methylation rate of FBLN1 promoter was significantly higher in CRC tissues than that in adjacent nontumor tissues (P < 0.001). In addition, the correlation between FBLN1 hypermethylation, protein expression, and overall survival (OS) was statistically significant.Our results indicated that the FBLN1 gene may be a novel candidate of tumor suppressor gene in CRC, and that promoter hypermethylation of FBLN1 is an important reason for its downregulation and is also a good predictor of OS for CRC.     

Somatic molecular changes and histo-pathological features of colorectal cancer in Tunisia

AIM:To determine correlations between family history,clinical features and mutational status of genes involved in the progression of colorectal cancer(CRC).METHODS:Histo-pathological features and molecular changes[KRAS,BRAF and CTNNB1 genes mutations,microsatellite instability(MSI)phenotype,expression of mismatch repair(MMR)and mucin(MUC)5AC proteins,mutation and expression analysis of TP53,MLH1promoter hypermethylation analysis]were examined in a series of 51 unselected Tunisian CRC patients,10 of them had a proven or probable hereditary disease,on the track of new tumoral markers for CRC susceptibility in Tunisian patients.RESULTS:As expected,MSI and MMR expression loss were associated to the presence of familial CRC(75%vs 9%,P<0.001).However,no significant associations have been detected between personal or familial cancer history and KRAS(codons 12 and 13)or TP53(exons 4-9)alterations.A significant inverse relationship has been observed between the presence of MSI and TP53 accumulation(10.0%vs 48.8%,P=0.0335)in CRC tumors,suggesting different molecular pathways to CRC that in turn may reflect different environmental exposures.Interestingly,MUC5AC expression was significantly associated to the presence of MSI(46.7%vs 8.3%,P=0.0039),MMR expression loss(46.7%vs8.3%,P=0.0039)and the presence of familial CRC(63%vs 23%,P=0.039).CONCLUSION:These findings suggest that MUC5AC expression analysis may be useful in the screening of Tunisian patients with high risk of CRC.     

MGMT and MLH1 methylation in Helicobacter pylori-infected children and adults

AIM:To evaluate the association between Helicobacter pylori(H.pylori) infection and MLH1 and MGMT methylation and its relationship with microsatellite instability(MSI).METHODS:The methylation status of the MLH1 and MGMT promoter region was analysed by methylation specific methylation-polymerase chain reaction(MSPPCR) in gastric biopsy samples from uninfected or H.pylori-infected children(n = 50),from adults with chronic gastritis(n = 97) and from adults with gastric cancer(n = 92).MLH1 and MGMT mRNA expression were measured by real-time PCR and normalised to a constitutive gene(β actin).MSI analysis was performed by screening MSI markers at 4 loci(Bat-25,Bat-26,D17S250 and D2S123) with PCR;PCR products were analysed by single strand conformation polymorphism followed by silver staining.Statistical analyses were performed with either the χ 2 test with Yates continuity correction or Fisher’s exact test,and statistical significance for expression analysis was assessed using an unpaired Student’s t-test.RESULTS:Methylation was not detected in the promoter regions of MLH1 and MGMT in gastric biopsy samples from children,regardless of H.pylori infection status.The MGMT promoter was methylated in 51% of chronic gastritis adult patients and was associated with H.pylori infection(P < 0.05);this region was methylated in 66% of gastric cancer patients,and the difference in the percentage of methylated samples between these patients and those from H.pylori-infected chronic gastritis patients was statistically significant(P < 0.05).MLH1 methylation frequencies among H.pylori-infected and non-infected chronic gastritis adult patients were 13% and 7%,respectively.We observed methylation of the MLH1 promoter(39%) and increased MSI levels(68%) in samples from gastric cancer patients in comparison to samples from H.pylori-infected adult chronic gastritis patients(P < 0.001 and P < 0.01,respectively).The frequency of promoter methylation for both genes was higher in gastric cancer samples than in H.pylori-positiv     

Downregulation of fibulin-3 gene by promoter methylation in colorectal cancer predicts adverse prognosis

Fibulin-3 gene has been identified as an antagonist of angiogenesis. We investigated the protein expression and promoter methylation status of fibulin-3 gene in colorectal cancer (CRC) and analyzed its correlation with clinicopathological factors. The study population enrolled 85 paired CRC specimens and adjacent normal tissues, as well as 32 cases of colorectal adenoma. Genomic DNA was extracted from paraffin-embedded samples using manual microdissection. Methylation-specific polymerase chain reaction (MSP) was used to determine the promoter methylation status and fibulin-3 gene expression was detected by immunohistochemistry. The results showed that, downregulation or silence of fibulin-3 protein was found in 57.6% (49/85) of CRC tissues, which was significantly higher than that of adjacent normal tissues (28.2%, 24/85) and colorectal adenoma (34.4%, 11/32) (P<0.05). Furthermore, 33 out of 85 (38.8%) CRC specimens showed hypermethylation in fibulin-3 promoter region, and fibulin-3 methylation was closely correlated with its loss of expression. Also, downregulation of fibulin-3 was associated with advanced stage (P=0.008) and lymph node metastasis (P=0.013). Survival analyses and Cox proportional hazard models indicated that fibulin-3 downregulation was an independent factor related to adverse overall survival (OS) and disease-free survival (DFS) of CRC. In conclusion, we found aberrant methylation caused fibulin-3 downregulation in CRC, and fibulin-3 downregulation was correlated with tumor stage, lymph node metastasis and poor survival, which maybe use as a potential prognostic factor for CRC.     

Semaphorin 4D and hypoxia-inducible factor-1α overexpression is related to prognosis in colorectal carcinoma

AIM:To investigate semaphorin 4D(Sema4D)and hypoxia-inducible factor-1α(HIF-1α)expression in colorectal carcinoma and evaluate their clinicopathological and prognostic significance.METHODS:Eighty-six curatively resected colorectal carcinoma patients at different stages of disease were randomly selected from the group of patients who underwent surgery,and none of them received preoperative radiochemotherapy.Normal proximal adjacent bowel tissue,which served as an internal control,was obtained from 52 randomly selected patients.Immunohistochemistry was performed to analyze the expression of Sema4D and the tumor angiogenesisrelated protein HIF-1αin normal colorectal tissues and colorectal carcinoma tissues.The relationships between the expression and clinical characters and prognosis were analyzed.RESULTS:HIF-1αand Sema4D were positively expressed in 58%and 60%of colorectal carcinoma tissues,respectively.Significantly lower expression levels were observed in normal mucosa(8%and 12%,respectively).HIF-1αand Sema4D expression was closely correlated with histological tumor type,tumornode-metastasis(TNM)stage,and lymphatic metastasis(P0.05),but not with age or tumor size(P0.05).HIF-1αand Sema4D protein expression was significantly correlated with prognosis of colorectal carcinoma,as determined by Spearman rank correlation analysis(r=0.567;P0.01).Multivariate Cox analysis revealed that only Sema4D expression played a significant role in predicting patient prognosis(P0.05).CONCLUSION:These findings suggest that HIF-1αand Sema4D expression correlates with histological tumor type,TNM stage,and lymphatic metastasis in colorectal carcinoma and that Sema4D is a prognostic indicator of colorectal carcinoma.     

Correlation between mitochondrial TRAP-1 expression and lymph node metastasis in colorectal cancer

AIM: To evaluate the effect of mitochondrial tumor necrosis factor receptor-associated protein-1 (TRAP-1) on the lymph node metastasis (LNM) in Chinese colorectal cancer (CRC) patients, and develop potential LNM-associated biomarkers for CRC using quantitative real-time polymerase chain reaction (RT-PCR) analysis.METHODS: Differences in mitochondrial TRAP-1 gene expression between primary CRC with LNM (LNM CRC) and without LNM (non-LNM CRC) were assessed in 96 Chinese colorectal carcinoma samples using quantitative RT-PCR analysis, Western blotting, and confirmed with immunohistochemical assay. The relationship between clinicopathological parameters and potential diagnostic biomarkers was also examined.RESULTS: TRAP-1 was significantly upregulated in LNM CRC compared with non-LNM CRC, which was confirmed by RT-PCR, Western blotting and immunohistochemical assay. The expression of TRAP-1 in two different metastatic potential human colorectal cancer cell lines, LoVo and HT29, was analyzed with Western blotting. The expression level of TRAP-1 was dramatically higher in LoVo than in HT29. Overexpression of TRAP-1 was significantly associated with LNM (90.2% in LNM group vs 22% in non-LNM group, P < 0.001), the advanced tumor node metastasis stage (89.1% in LNM group vs 26.9% in non-LNM group, P < 0.001), the increased 5-year recurrence rate (82.7% in LNM group vs 22.6% in non-LNM group, P < 0.001) and the decreased 5-year overall survival rate (48.4% in LNM vs 83.2% in non-LNM group, P < 0.001). Univariate and multivariate analyses indicated that TRAP-1 expression was an independent prognostic factor for recurrence and survival of CRC patients (Hazard ratio of 2.445 in recurrence, P = 0.017; 2.867 in survival, P = 0.028).CONCLUSION: Mitochondria TRAP-1 affects the lymph node metastasis in CRC, and may be a potential biomarker for LNM and a prognostic factor in CRC. Over-expression of TRAP-1 is a predictive factor for the poor outcome of colorectal cancer patients.     

Combined detection of plasma GATA5 and SFRP2 methylation is a valid noninvasive biomarker for colorectal cancer and adenomas

AIM:To investigate GATA5,SFRP2,and ITGA4 methylation in plasma DNA as noninvasive biomarkers for colorectal cancer(CRC) or adenomas.METHODS:There were 57 CRC patients,30 adenomas patients,and 47 control patients enrolled in this study.Methylation-specific polymerase chain reaction was used to determine the promoter methylation status of GATA5,SFRP2,and ITGA4 genes in plasma DNA,and their association with clinical outcome in CRC.The predictive ability of GATA5,SFRP2,and ITGA4 methylation,individually or in combination,to detect CRC or adenomas was further analyzed.RESULTS:Hypermethylated GATA5 was detected in plasma in 61.4%(35/57) of CRC cases,43.33%(13/30) of adenoma cases,and 21.28%(10/47) of control cases.The hypermethylation of SFRP2 was detected in 54.39%(31/57),40.00%(12/30),and 27.66%(13/47) in plasma samples from CRC,adenomas,and controls,respectively.ITGA4 methylation was detected in 36.84%(21/57) of plasma samples of CRC patients and in 30.00%(9/30) of plasma samples from patients with colorectal adenomas,and the specificity of this individual biomarker was 80.85%(9/47).Moreover,GATA5 methylation in the plasma was significantly correlated with larger tumor size(P =0.019),differentiation status(P =0.038),TNM stage(P =0.008),and lymph node metastasis(P =0.008).SFRP2 and ITGA4 methylation in plasma significantly correlated with differentiation status(SFRP2,P =0.012; ITGA4,P =0.007),TNM stage(SFRP2,P =0.034; ITGA4,P =0.021),and lymph node metastasis(SFRP2,P =0.034; ITGA4,P =0.021).From the perspective of predictive power and cost-performance,using GATA5 and SFRP2 together as methylation markers seemed the most favorable predictor for CRC(OR =8.06;95%CI:2.54-25.5; P < 0.01) and adenomas(OR =3.35; 95%CI:1.29-8.71; P =0.012).CONCLUSION:A combination of GATA5 and SFRP2 methylation could be promising as a marker for the detection and diagnosis of CRC and adenomas.     

Correlational research of Golgi phosphorylation protein 3 expression in colorectal cancer

AIM: To investigate the effect of Golgi phosphorylation protein 3 (GOLPH3) expression on cell apoptosis, angiogenesis and prognosis in colorectal cancer (CRC).METHODS: The expression of GOLPH3 in CRC tissues and normal colorectal mucosae was determined by immunohistochemistry in 62 patients. In addition, immunohistochemistry was also carried out to detect the expression of vascular endothelial growth factor (VEGF), CD34 and microvessel density (MVD). Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay was used to determine the apoptotic index (AI). The Kaplan-Meier method was used to analyze the relationship between GOLPH3 expression and survival in another 123 CRC cases.RESULTS: Compared with normal colorectal mucosae, a notably higher level of GOLPH3 protein expression was identified in CRC tissues (53.2% vs 24.2%, P < 0.05). Positive GOLPH3 expression was significantly associated with tumor invasion depth, TNM stage, and lymph node metastasis (P = 0.001; P = 0.020; P = 0.020; P < 0.05, respectively), but not with tumor length, tumor site, and age (P = 0.363; P = 0.819; P = 0.599; P > 0.05, respectively). VEGF expression and MVD in GOLPH3-positive CRC was significantly higher than in GOLPH3-negative CRC (VEGF: 69.7% vs 31.0%; MVD: 21.45 ± 9.39 vs 14.24 ± 8.97; P < 0.05). GOLPH3 expression was negatively correlated with AI in CRC as shown by Spearman correlation analysis (r = -0.320, P < 0.05). The 5-year survival rate in GOLPH3-negative CRC (69.4%) was significantly higher than in GOLPH3-positive CRC (48.6%) (log-rank test, P < 0.05).CONCLUSION: High expression of GOLPH3 is found in CRC tissues. GOLPH3 expression may be a novel prognostic marker for CRC patients.     

Decreased expression of miR-133a correlates with poor prognosis in colorectal cancer patients

AIM: To investigate microRNA-133a (miR-133a) expression in colorectal cancer (CRC) and its relationship with tumorigenesis and disease prognosis.METHODS: Quantitative real-time polymerase chain reaction was used to measure levels of miR-133a in tumor samples and adjacent non-cancerous tissues from 169 patients undergoing radical resection for CRC. The associations between miR-133a expression and patient age, sex, as well as clinicopathologic parameters, such as tumor size, differentiation, location, invasion depth, metastasis, tumor-node-metastasis (TNM) stage and overall patient survival, were analyzed by Mann-Whitney U and Kruskal-Wallis tests. The Kaplan-Meier method and Cox proportional hazards regression analyses were performed to estimate the prognostic factors for patient survival prediction.RESULTS: The expression of miR-133a was significantly downregulated in CRC tissues compared with adjacent non-cancerous tissues (P < 0.05). This reduction was associated with the depth of the local invasion, poor differentiation, lymph node metastasis and advanced disease (P < 0.05). Moreover, Kaplan-Meier analysis demonstrated that patients with low miR-133a expression had poorer overall survival (OS) than those with high miR-133a expression (P < 0.001). Univariate analysis revealed statistically significant correlations between OS and miR-133a level, tumor local invasion, lymph node metastasis and TNM stage (P < 0.001). Furthermore, miR-133a levels and TNM stage were independently associated with OS (HR = 0.590, 95%CI: 0.350-0.995, P < 0.05; and HR = 6.111, 95%CI: 1.029-36.278, P < 0.05, respectively).CONCLUSION: The downregulation of miR-133a may play an important role in the progression of CRC and can be used as an independent factor to determine CRC prognosis.