Overexpression of BIRC6 Is a Predictor of Prognosis for Colorectal Cancer.
Ontology highlight
ABSTRACT: Background and objective
Inhibitors of apoptosis proteins (IAPs) have been well investigated in human cancers, where they are frequently overexpressed and associated with poor prognosis. Here we explored the role of baculoviral IAP repeat containing 6 (BIRC6), a member of IAPs, in human colorectal cancer (CRC).Methods
We used Western blotting and immunohistochemistry to examine BIRC6 expression in 7 CRC cell lines and 126 CRC clinical samples. We determined the biological significance of BIRC6 in CRC cell lines by a lentivirus-mediated silencing method.Results
We reported that BIRC6 was overexpressed in CRC cell lines and clinical CRC tissues. BIRC6 overexpression was correlated with tumor size and invasion depth of CRC. BIRC6 overexpression is associated with worse overall survival (OS) (P = 0.001) and shorter disease-free survival (DFS) (P = 0.010). BIRC6 knockdown inhibited cell proliferation, arrested cell cycle at S phase, downregulated cyclin A2, B1, D1 and E1 levels, and sensitized CRC cells to chemotherapy in vitro and in vivo.Conclusions
Taken together, these data suggests that BIRC6 overexpression is a predictor of poor prognosis in colorectal cancer and BIRC6 could be a potential target of CRC therapy.
SUBMITTER: Hu T
PROVIDER: S-EPMC4416929 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundStructural maintenance of chromosomes 1A (SMC1A) is a member of the cohesion family of proteins that plays crucial roles in cell cycle control. Recent studies have concluded that SMC1A is involved in the pathogenesis of cancer. This study aims to evaluate the functional role of SMC1A in colorectal cancer (CRC) both in vitro and in vivo, and the underlying molecular mechanisms.MethodsWe firstly investigated the expression levels of SMC1A in 427 CRC specimens. Antigen expression was determined by immunohistochemical analysis of SMC1A on tissue microarrays. Stable SMC1A knockdown CRC cell lines were employed. The effects of SMC1A depletion on cell growth in vitro were examined by MTT, colony formation and flow cytometry assays. Tumor forming was evaluated by nude mice model in vivo. To detect the activation of intracellular signaling, pathscan intracellular signaling array and western blotting were performed.ResultsThe expression of SMC1A was much stronger in CRC tumor tissues than in adenomas and normal colorectal tissues. High SMC1A expression, indicated as an independent poor prognostic predictor for patients with stage III and stage IV CRC, was correlated with overall survival (OS) (p = 0.008). Functional analysis indicated that SMC1A knockdown by small interfering RNA (siRNA) mediated the significant inhibition of cell proliferation; induced cell cycle arrest and apoptosis via the suppression of CDK4, PCNA and PARP; and blocked the activation of the Erk1/2 and Akt cascades in CRC cells. In addition, SMC1A depletion significantly decreased the growth of subcutaneously inoculated tumors in nude mice.ConclusionsThese results suggest that SMC1A plays an essential role in the development of CRC and may be a predictive factor in patients with CRC. The inhibition of SMC1A may serve as a promising therapeutic strategy for human CRC.
| S-EPMC4352287 | biostudies-literature
Project description:BackgroundThe long non-coding RNA (lncRNA) prostate cancer-associated transcript 6 (PCAT6) has been studied in many cancers, yet its relationship with colorectal cancer (CRC) remains poorly defined. Here, we conducted an analysis of The Cancer Genome Atlas (TCGA) database to better clarify the role of PCAT6 in this cancer type.MethodsWilcoxon rank-sum tests were utilized to assess relative levels of PCAT6 in CRC tumors and normal tissues, while logistic regression analyses were utilized to compare the relationships between PCAT6 levels and clinicopathological findings. Kaplan-Meier curves and Cox regression analyses were used to gauge correlations between PCAT6 and patient survival outcomes, while the biological roles of this lncRNA were investigated via a gene set enrichment analysis (GSEA) approach. The expression level of PCAT6 in CRC cell lines was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR).ResultsPCAT6 levels were significantly correlated with CRC patient lymph node metastasis (N) stage [odds ratio (OR) =1.8 for N1 & N2 vs. N0], lymphatic invasion [OR =1.9 for yes vs. no), distant metastasis (M stage) (OR =2.1 for M1 vs. M0), carcinoembryonic antigen (CEA) level (OR =1.9 for >5 vs. ≤5), perineural invasion (OR =1.9 for yes vs. no), pathologic stage (OR =1.9 for stage III/IV vs. stage I/II), and neoplasm type (OR =2.1 for rectal adenocarcinoma vs. colon adenocarcinoma) (all P<0.05). CRC patients expressing higher PCAT6 levels exhibited poorer survival outcomes than those expressing low levels of this lncRNA (P=0.017), and in univariate analyses, higher PCAT6 levels were linked to worse overall survival [hazard ratio (HR) =1.540; 95% confidence interval (CI): 1.079-2.199; P=0.017], with this relationship also being preserved in a multivariate analysis (HR =6.892; 95% CI: 1.713-27.727, P=0.007). GSEA revealed high PCAT6 expression to be linked to differential DNA methylation enrichment, with high PCAT6 levels being associated with changes in base excision repair, cellular senescence, G2/M DNA damage checkpoint, chromatin-modifying enzyme, and gene silencing by RNA activity. The high expression of lncRNA PCAT6 in CRC cell lines was demonstrated by PCR experiments.ConclusionsPCAT6 represents a promising prognostic biomarker of poor CRC patient survival outcomes, with DNA methylation and RNA-mediated gene silencing being potentially promising mechanistic pathways whereby this lncRNA may shape patient outcomes.
| S-EPMC10932681 | biostudies-literature
Project description:BackgroundBladder cancer is one of the most common urinary malignancies. This study is aimed at providing some promising molecular biomarkers for bladder cancer (BC) by investigating the correlation between C1QTNF6 expression and clinical characteristics as well as prognosis in patients with bladder cancer.MethodsSequencing profiles of C1QTNF6 mRNA in BC patients were collected to evaluate the distinctive gene expression, between normal bladder mucosa and BC, according to the TCGA and GEO databases. The association between C1QTNF6 expression and the clinical features as well as the disease prognosis was evaluated using two independent cohorts. The expression of C1QTNF6 in normal bladder and BC cells was examined by western blotting and PCR, so the underlying molecular mechanism could be further investigated.ResultsC1QTNF6 mRNA levels were found to be differentially expressed in two independent public cohorts, including the TCGA database and GSE13507 dataset from GEO. The protein and RNA levels of C1QTNF6 in BC cells were both elevated when compared to normal bladder cell lines. High C1QTNF6 expression was detected in advanced T/M stages, pathological grade, and AJCC stage when compared to the low C1QTNF6 expression group. The underlying mechanism related to this differential expression could be explained by cell migration and invasion assays, where bladder cancer cells 5637 and T24 had a significant reduction on migration and invasion ability upon knockdown of C1QTNF6 expression. The low C1QTNF6 expression group presented a more prominent OS advantage over the high-expression group in both TCGA and GSE13507 cohorts. Moreover, the protein content in tissues was further validated using the HPA database and TMA. Survival analyses also indicated that the high C1QTNF6 expression group had an unfavorable OS when compared to the low-expression group.ConclusionsHigh C1QTNF6 expression may serve as a predictor of poor prognosis in bladder cancer patients, and the underlying mechanism is possibly associated with changes on cancer cell migration and invasion ability.
| S-EPMC7585664 | biostudies-literature
Project description:Bone morphogenetic proteins (BMPs) both promote and suppress tumorigenesis, and multiple BMP antagonists reportedly contribute to cancer progression. In this study, we demonstrated that the BMP antagonist Chordin-like 2 (CHRDL2) is upregulated in colorectal cancer (CRC) tissues, and that CHRDL2 levels correlate with clinical features of CRC patients, including tumor size, TNM staging, and tumor differentiation. In addition, survival rate and Cox proportional hazards model analyses showed that high CHRDL2 levels correlate with a poor prognosis in CRC. Moreover, CHRDL2 promoted CRC cell proliferation in vitro and in vivo, perhaps through up-regulation of Cyclin D1 and down-regulation of P21. Co-immunoprecipitation assays showed that CHRDL2 bound to BMPs, which inhibited p-Smad1/5, thereby promoting CRC cell proliferation and inhibiting apoptosis. These results suggest CHRDL2 could serve as a biomarker of poor prognosis in CRC, and provide evidence that CHRDL2 acts as an oncogene in human CRC, making it a novel potential therapeutic target.
| S-EPMC5355280 | biostudies-literature
Project description:Background and objectiveYes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are nuclear effectors of the Hippo pathway. Although they are abundantly expressed in the cytoplasm and nuclei of human colorectal cancer (CRC), and related to tumor proliferation status, there have been few studies on the predictive role of YAP and TAZ expression on the overall survival of patients with CRC. This study investigated YAP and TAZ expression in both CRC patients and colon cancer cell lines, and assessed their prognostic value.MethodsParaffin-embedded specimens from 168 eligible patients were used to investigate YAP and TAZ expression by immunohistochemistry, and compared with experimental results in colon cancer HCT116 cell line to explore their clinical significance in CRC.ResultsStatistically significant positive correlations were found between protein expression of YAP and TAZ in CRC tissues. Patients with higher YAP or TAZ expression showed a trend of shorter survival times; more importantly, our cohort study indicated that patients with both YAP and TAZ overexpression presented the worst outcomes. This was supported by multivariate analysis. In HCT116 colon cancer cells, the capacity for proliferation, metastasis, and invasion was dramatically reduced by knockdown of YAP and TAZ expressions by siRNA.ConclusionsCo-overexpression of YAP and TAZ is an independent predictor of prognosis for patients with CRC, and may account for the higher proliferation, metastasis, and poor survival outcome of these patients.
| S-EPMC3677905 | biostudies-literature
Project description:Colorectal cancer is a heterogeneous disease. Although many risk factors are used to predict colorectal cancer patients' prognosis after surgical resection, new prognostic factors are still needed to be defined to promote predictive efficacy of prognosis and further guide therapies. Herein, we identified the prognostic significance of CXCR2 in colorectal cancer patients. We retrospectively analysed 134 patients with colorectal cancer who underwent minimally invasive surgery between 2010 and 2011. The overall cohort was divided into a training set (n = 78) and a validation set (n = 56). We detected CXCR2 expression using immunohistochemical staining and defined the cut-off value using X-tile program. Next, we analysed the association between CXCR2 expression and clinicopathologic features in training and validation sets. High expression of CXCR2 was associated with Dukes stage (P = 0.018), tumor invasion (P = 0.018) and liver metastasis (P = 0.047). Multivariate COX regression analyses confirmed that high CXCR2 level was an independent prognostic risk factor for both overall survival and disease free survival. Kaplan-Meier survival analysis demonstrated that patients with high expression of CXCR2 had a poor overall survival and disease free survival even in low-risk group (I + II). This indicated that CXCR2 can help to refine individual risk stratification. In addition, we established Nomograms of all significant factors to predict 3- or 5-years overall survival and disease free survival. Moreover, we found the combination of CXCR2 and its ligand CXCL5 had more significant value in predicting the prognosis than single CXCR2 factor.
| S-EPMC5438662 | biostudies-literature
Project description:BACKGROUND: Colorectal cancer (CRC) remains one of the most common cancers worldwide. We observed that MUC20 was significantly up-regulated in CRC patients with poor prognosis based on the microarray analysis. However, little is known about the role of MUC20 in CRC. METHODS: Microarray experiments were performed on the Affymetrix U133 plus 2.0 GeneChip Array. The protein and mRNA levels of MUC20 were examined by immunohistochemistry (IHC) and Real-Time quantitative PCR (RT-qPCR) in CRC tissues and adjacent noncancerous tissues (ANCT). ShRNA and overexpression plasmids were used to regulate MUC20 expression in CRC cell lines in vitro; wound healing, Transwell migration assays, and Western blotting were used to detect migration and invasion changes. RESULTS: MUC20 was one of the up-regulated genes in CRC patients with poor prognosis by microarray. Using IHC and RT-qPCR, we showed that MUC20 expression was significantly higher in CRC tissues than in ANCT (P?<?0.05). We further showed that MUC20 overexpression was correlated with recurrence and poor outcome (P?<?0.05). The Kaplan-Meier survival curves indicated that disease-free survival (DFS) and overall survival (OS) were significantly worse in CRC patients with MUC20 overexpression. The Cox multivariate analysis revealed that MUC20 overexpression and TNM stage were independent prognostic factors. Elevated expression of MUC20 in cells promoted migration and invasion, whereas ShRNA-mediated knockdown inhibited these processes. In addition, Western blotting demonstrated that MUC20-induced invasion was associated with MMP-2, MMP-3, and E-cadherin. CONCLUSIONS: Cumulatively, MUC20 may serve as an important predictor of recurrence and poor outcome for CRC patients. MUC20 overexpression could enhance migration and invasion abilities of CRC cells. Translation of its roles into clinical practice will need further investigation and additional test validation.
| S-EPMC3702436 | biostudies-literature
Project description:α-taxilin is a binding partner of syntaxins, which are the central coordinators of membrane traffic. Expression of α-taxilin has been implicated in the development of human glioblastoma, hepatocellular carcinoma and renal cell carcinoma. In the present study, the clinical significance of α-taxilin expression in colorectal cancer (CRC) was investigated. A total of 20 cases of colorectal intramucosal adenocarcinoma (IMA) with adenoma were analyzed using immunohistochemical analysis. The results demonstrated that α-taxilin expression was significantly associated with Ki-67 indices in adenoma and IMA. The patients expressed equally high levels of α-taxilin in the upper third of the intramucosal glands. These results suggest that α-taxilin expression is significantly associated with the proliferative activity of CRC, but that its overexpression alone is not a biomarker of malignancy. Next, α-taxilin expression was investigated in 57 advanced CRCs and its association with prognosis was determined. Well-differentiated and/or moderately differentiated adenocarcinomas in the left-sided colon with anatomic stage II and/or III were analyzed. α-taxilin expression levels were high on the surface of nearly all tumors, but variable at the deep advancing edge. α-taxilin levels at the advancing edge were not significantly associated with local invasiveness or prognosis. In conclusion, α-taxilin is a cell proliferation marker in colorectal epithelial neoplasms but cannot be a marker of malignancy or prognosis of CRCs.
| S-EPMC5529874 | biostudies-other
Project description:ObjectivesDown syndrome critical region 1 (DSCR1) is associated with carcinogenesis and tumor growth in several types of malignancy. However, little is known about the role of DSCR1 in CRC progression. The present study aimed to elucidate the clinicopathological significance, prognostic, and function roles of DSCR1 in CRC.MethodsFirstly, we analyzed DSCR1 expression in 58 paired CRC samples and Oncomine database. Then, we analyzed DSCR1 expression in two independent CRC cohorts (test cohort: n = 70; validation cohort: n = 58) and tested its overall survival (OS) by Kaplan-Meier survival analyses. Finally, we overexpressed DSCR1 in two CRC cell lines DLD1 and LoVo and analyzed its effect on cell cycle and senescence.ResultsDSCR1 expression was significantly decreased in CRC samples and associated with clinicopathologic features of CRC patients, such as tumor size, lymph node metastasis, and TNM stage. CRC patients with low expression of DSCR1 had shorter overall survival (OS). Kaplan-Meier survival analyses showed that the expression of DSCR1 was significant factor for OS in both cohorts. Multiple Cox regression analysis showed that DSCR1 expression was an independent prognostic marker for OS in test cohort. Overexpression of DSCR1 isoform 4 (DSCR1-4) increased p21, p16, p-NFAT1, and p-NFAT2, while decreased CDK2, CDK4, and Cyclin D1 in CRC cells. In addition, overexpression of DSCR1-4 prevented proliferation and colony formation, and induced senescence in vitro. Moreover, overexpression of DSCR1-4 inhibited tumor growth and tumor angiogenesis in vivo.ConclusionsOur study found high expression of DSCR1 contributes to favorable prognosis of CRC patients and prevents cell cycle and proliferation of CRC cells, indicating a critical tumor suppressive role in CRC progression.
| S-EPMC8028816 | biostudies-literature
Project description:Tumor metastasis and anticancer drug resistance are the major causes of mortality in patients with colorectal cancer (CRC). Due to the limitations of conventional biomarkers, it is urgent to identify novel and valid biomarkers to predict the progression and prognosis of CRC. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect MAGT1 expression in CRC clinical samples or cell lines. Bioinformatics analysis was used to investigate the association between MAGT1 alteration and clinicopathological features of patients with CRC. The present study revealed that the transcription levels of magnesium transporter 1 (MAGT1) were significantly increased in CRC tissues compared with matched adjacent normal tissues. Overexpression of MAGT1 was associated with advanced tumor stage, N and M classification. In addition, for patients who underwent chemotherapy, patients in the MAGT1-low expression group exhibited a longer overall survival (OS) time than patients in the high-expression group. Patients with CRC treated with chemotherapy had a longer OS time than those treated without chemotherapy in the MAGT1-low expression group but not in the MAGT1-high expression group. Furthermore, MAGT1 was a valid but not an independent prognostic factor for CRC. Therefore, the present study highlighted that MAGT1 may serve as a valid biomarker for predicting the development, progression and poor prognosis of CRC.
| S-EPMC6732944 | biostudies-literature