scholarly journals The Clinical Implications and Molecular Mechanism of CX3CL1 Expression in Urothelial Bladder Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Guangliang Jiang ◽  
Hui Wang ◽  
Da Huang ◽  
Yishuo Wu ◽  
Weihong Ding ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Mapk Signaling ◽  
High Expression ◽  
Pathway Enrichment Analysis ◽  
Cancer Specific Survival ◽  
Cox Regression Analysis

BackgroundCX3CL1 is a chemokine that may play important roles in cancer immune regulation. Its mechanism in bladder cancer (BCa) is poorly understood. The objective of the current study was to evaluate the association between CX3CL1 and BCa and the related biological mechanisms.MethodsA total of 277 patients with BCa were enrolled in the present study. The association between CX3CL1 expression and disease outcome was evaluated. In vitro and in vivo experiments were performed using the TCCSUP cell line to investigate the function of CX3CL1 in BCa.ResultsCompared with low expression, high expression of CX3CL1 was significantly associated with poorer progression-free survival (hazard ratio [HR]=2.03, 95% confidence interval [95% CI]: 1.26-3.27, P=0.006), cancer-specific survival (HR=2.16, 95% CI: 1.59-2.93, P<0.001), and overall survival (HR=1.55, 95% CI: 1.08-2.24, P=0.039). Multivariable Cox regression analysis suggested that CX3CL1 was an independent prognostic factor for BCa outcomes. In vitro and in vivo experiments indicated that high expression of CX3CL1 was significantly associated with cell proliferation (P<0.001) and invasion (P<0.001). Gene expression profiling results showed that after CX3CL1 knockdown, CDH1 was significantly upregulated, while ETS1, RAF1, and EIF4E were significantly downregulated. Pathway enrichment analysis suggested that the ERK/MAPK signaling pathway was significantly inhibited (P<0.001).ConclusionsCX3CL1 is an independent predictor of a poor prognosis in BCa and can promote the proliferation and invasion of BCa cells.

scholarly journals MCM7 promotes cancer progression through cyclin D1-dependent signaling and serves as a prognostic marker for patients with hepatocellular carcinoma

2017 ◽  
Vol 8 (2) ◽  
pp. e2603-e2603 ◽  
Author(s):  
Kai Qu ◽  
Zhixin Wang ◽  
Haining Fan ◽  
Juan Li ◽  
Jie Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Replication ◽  
Cyclin D1 ◽  
Cancer Progression ◽  
Cellular Proliferation ◽  
High Sensitivity ◽  
Mapk Signaling ◽  
High Expression

Abstract DNA replication is a central procedure of cell proliferation, whereas aberrant DNA replication is indicated to be a driving force of oncogenesis. Minichromosome maintenance complex component 7 (MCM7) plays an essential role in initiating DNA replication. To investigate the potential oncogenic properties and prognostic value of MCM7 in hepatocellular carcinoma (HCC), we conducted immunohistochemistry staining of MCM7 in 153 HCC samples and found that MCM7 high expression level was associated with worse overall survival (OS) of HCC patients. Mechanistically, knockdown of MCM7 significantly inhibited cellular proliferation in vitro and HCC tumorigenicity in vivo. Cyclin D1 was proved to be regulated by MCM7–MAPK signaling pathway. Clinically, high expression of both MCM7 and cyclin D1 exhibited a relatively high sensitivity and specificity to predict worse outcome of HCC patients. Taken together, our results suggest that MCM7–cyclin D1 pathway may participate in cancer progression and serve as a biomarker for prognosis in HCC.

SLFN11 expression (exp) in castration-resistant prostate cancer (CRPC) patients (pts) to predict response to platinum-based chemotherapy (PLT).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5065-5065
Author(s):  
Vincenza Conteduca ◽  
Loredana Puca ◽  
Sheng-Yu Ku ◽  
Judy Hess ◽  
Megan Kearney ◽  
...  
Keyword(s):  
Cox Regression ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Median Number ◽  
Parp Inhibitors ◽  
Castration Resistant Prostate Cancer ◽  
Cox Regression Analysis ◽  
Platinum Based Chemotherapy

5065 Background: Schlafen family member 11 (SLFN11) sensitizes tumor cells to DNA-damaging agents and has been investigated as a potential predictive biomarker of response to PLT and PARP inhibitors, especially in small cell lung cancer (Lok, CCR 2017; Pietanza, JCO 2018). We aimed to explore the predictive/prognostic role of SLFN11 in PLT-treated CRPC. Methods: We assessed tumor exp of SLFN11 in PLT-treated, metastatic CRPC pts by RNAseq (N=27) and/or CTCs (N=20) (via the Epic Sciences platform). In addition, tumor morphology for neuroendocrine (NE) features and genomic status of select genes (ie, AR, TP53, RB1, BRCA2, BRCA1, ATM) by whole exome sequencing were evaluated. Statistical comparisons used Cox regression analysis and Kaplan Meier method for the association with overall/radiographic progression free survival (OS/rPFS). A dose response curve with PLT was performed in patient-derived organoids using Cell Title Glo according to the manufacturer’s protocol. Results: 41 CRPC (including 20 CRPC-NE) treated with PLT monotherapy (N=3) or PLT combination therapy (N=38) between August 2013 and December 2017 were evaluated. Median age was 67.1 years (range 51-91). Median number of prior therapies was 2 (range 1-7). A longer median rPFS was observed in all SLFN11+ pts treated with PLT (regardless of histology, RB1, TP53, PTEN, or DNA repair status) compared to SLFN11- [5.2 vs 2.3 months, HR 3.5, 95%CI 1.6-7.7, P<0.0001]. No association was reported for OS. On multivariable analysis (Table), SLFN11 was an independent factor associated with rPFS. Organoids derived from patient tumors expressing SLFN11 showed sensitivity to PLT in vitro. Conclusions: SLFN11 exp identifies both CRPC and CRPC-NE pts with a better response to PLT. Patient-derived organoids expressing SLFN11 confirmed increased sensitivity to PLT. Larger prospective evaluation of therapy decisions based on SLFN11 exp is now required. [Table: see text]

scholarly journals Long noncoding RNA RP11-757G1.5 sponges miR-139-5p and upregulates YAP1 thereby promoting the proliferation and liver, spleen metastasis of colorectal cancer

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Xiaojian Zhu ◽  
Fanqin Bu ◽  
Ting Tan ◽  
Qilin Luo ◽  
Jinfeng Zhu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
In Situ Hybridization ◽  
Cox Regression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cox Regression Analysis

Abstract Background Accumulating evidence indicates that long non-coding RNAs (lncRNAs) acting as crucial regulators in tumorigenesis. However, its biological functions of lncRNAs in colorectal cancer (CRC) have not been systematically clarified. Methods An unbiased screening was performed to identify disregulated lncRNAs revealed to be implicated in CRC carcinogenesis according to an online-available data dataset. In situ hybridization (ISH), RT-qPCR and RNA fluorescence in situ hybridization (RNA-FISH) were applied to detect RP11-757G1.5 expression in CRC tissues and cell lines. The associations of RP11-757G1.5 with clinicopathological characteristics were analyzed. Their effects on prognosis were analyzed by the Kaplan-Meier analysis, Log-rank test, Univariate and Multivariate Cox regression analysis. The potential biological function of RP11-757G1.5 in CRC was investigated by Colony formation, Edu cell proliferation, Flow cytometry, Wound healing and Transwell assays. Bioinformatics binding site analysis, Luciferase reporter assay, Ago2 immunoprecipitation assays, RNA pull-down assay, RT-qPCR and Western blotting were utilized to demonstrate the mechanism of RP11-757G1.5 acts as a molecular sponge of miR-139-5p to regulate the expression of YAP1. Finally, we further explore the potential role of RP11-757G1.5 in CRC orthotopic xenografts in vivo. Results We discovered a novel oncogenic lncRNA RP11-757G1.5, that was overexpressed in CRC tissues, especially in aggressive cases. Moreover, up-regulation of RP11-757G1.5 strongly correlated with poor clinical outcomes of patients with CRC. Functional analyses revealed that RP11-757G1.5 promoted cell proliferation in vitro and in vivo. Furthermore, RP11-757G1.5 stimulated cell migration and invasion in vitro and in vivo. Mechanistic studies illustrated that RP11-757G1.5 regulated the expression of YAP1 through sponging miR-139-5p and inhibiting its activity thereby promoting CRC progression and development. Conclusions Altogether, these results reveal a novel RP11-757G1.5/miR-139-5p/YAP1 regulatory axis that participates in CRC carcinogenesis and progression.

scholarly journals Does Health Insurance Modify the Association Between Race and Cancer-Specific Survival in Patients with Urinary Bladder Malignancy in the U.S.?

2019 ◽  
Vol 16 (18) ◽  
pp. 3393
Author(s):  
Juliana Morales ◽  
Aaron Malles ◽  
Marrell Kimble ◽  
Pura Rodriguez de la Vega ◽  
Grettel Castro ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Health Insurance ◽  
Urinary Bladder ◽  
Cox Regression ◽  
Cancer Surveillance ◽  
Urinary Bladder Carcinoma ◽  
Insurance Status ◽  
Cancer Specific Survival ◽  
Poor Prognostic Factor ◽  
Cox Regression Analysis

Background: Scientific evidence on the effect of health insurance on racial disparities in urinary bladder cancer patients’ survival is scant. The objective of our study was to determine whether insurance status modifies the association between race and bladder cancer specific survival during 2007–2015. Methods: The 2015 database of the cancer surveillance program of the National Cancer Institute (n = 39,587) was used. The independent variable was race (White, Black and Asian Pacific Islanders (API)), the main outcome was cancer specific survival. Health insurance was divided into uninsured, any Medicaid and insured. An adjusted model with an interaction term for race and insurance status was computed. Unadjusted and adjusted Cox regression analysis were applied. Results: Health insurance was a statistically significant effect modifier of the association between race and survival. Whereas, API had a lower hazard of death among the patients with Medicaid insurance (HR 0.67; 95% CI 0.48–0.94 compared with White patients, no differences in survival was found between Black and White urinary bladder carcinoma patients (HR 1.24; 95% CI 0.95–1.61). This may be due a lack of power. Among the insured study participants, Blacks were 1.46 times more likely than Whites to die of bladder cancer during the 5-year follow-up (95% CI 1.30–1.64). Conclusions: While race is accepted as a poor prognostic factor in the mortality from bladder cancer, insurance status can help to explain some of the survival differences across races.

scholarly journals Intravesical Bacillus Calmette–Guérin Treatment for T1 High-Grade Non-Muscle Invasive Bladder Cancer with Divergent Differentiation or Variant Morphologies

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2615
Author(s):  
Makito Miyake ◽  
Nobutaka Nishimura ◽  
Kota Iida ◽  
Tomomi Fujii ◽  
Ryoma Nishikawa ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cox Regression ◽  
World Health ◽  
High Grade ◽  
Bacillus Calmette Guerin ◽  
Cancer Specific Survival ◽  
Cox Regression Analysis ◽  
Divergent Differentiation ◽  
Intravesical Bcg ◽  
The Impact

The 2016 World Health Organization classification newly described infiltrating urothelial carcinoma (UC) with divergent differentiation (DD) or variant morphologies (VMs). Data comparing oncological outcomes after bladder-preservation therapy using intravesical Bacillus Calmette–Guérin (BCG) treatment among T1 bladder pure UC (pUC), UC with DD (UC-DD), and UC with VMs (UC-VM) are limited. We evaluated 1490 patients with T1 high-grade bladder UC who received intravesical BCG during 2000–2019. They were classified into three groups: 93.6% with pUC, 4.4% with UC-DD, and 2.0% with UC-VM. Recurrence-free, progression-free, and cancer-specific survival following intravesical BCG were compared among the groups using multivariate Cox regression analysis, also used to estimate inverse probability of treatment weighting-adjusted hazard ratio and 95% confidence interval for the outcomes. Glandular differentiation and micropapillary variant were the most common forms in the UC-DD and UC-VM groups, respectively. Of 1490 patients, 31% and 13% experienced recurrence and progression, respectively, and 5.0% died of bladder cancer. Survival analyses revealed the impact of concomitant VMs was significant for cancer-specific survival, but not recurrence-free and progression-free survival compared with that of pUC. Our analysis clearly demonstrated that concomitant VMs were associated with aggressive behavior in contrast to concomitant DD in patients treated with intravesical BCG.

scholarly journals Targeting tumor cell-derived CCL2 as a strategy to overcome bevacizumab resistance in ETV5+ colorectal cancer

2020 ◽  
Author(s):  
Haoran Feng ◽  
Kun Liu ◽  
Juyong Liang ◽  
Changgang Wang ◽  
Weihua Qiu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Candidate Gene ◽  
Tumor Angiogenesis ◽  
Antiangiogenic Therapy ◽  
Mapk Signaling ◽  
High Expression ◽  
Therapy Strategy ◽  
Investigation Methods

Abstract Background ETV5 mediated angiogenesis was dependent on PDGF-BB/PDGFR-β/Src/STAT3/VEGFA pathway in colorectal cancer (CRC) in our previous study. However, whether ETV5 affects effect of antiangiogenic therapy in CRC requires further investigation. Methods GSEA analysis and a series of experiments were performed to identify the critical candidate gene involved in bevacizumab resistance, and further explored whether the treatment targeting the candidate gene enhanced bevacizumab sensitivity in vitro and in vivo. Results ETV5 could directly bind to VEGFA promoter and promote translation of VEGFA. However, by in vitro and in vivo experiments, ETV5 actually accelerated anti-VEGF therapy (bevacizumab) resistance. GSEA analysis and further assays confirmed that ETV5 could promote angiogenesis by enhancing secretion of another tumor angiogenesis factor CCL2 in CRC cells, which resulted in bevacizumab resistance. ETV5 induced VEGFA and CCL2 were mutually independent to induce angiogenesis by activating PI3K/AKT and p38/MAPK signaling pathways in human umbilical vein endothelial cells. In CRC tissues, ETV5 protein level was positively associated with CD31, CCL2, VEGFA protein expression. CRC patients with high expression of ETV5/VEGFA or ETV5/CCL2 showed inferior prognosis than other patients. Combination of anti-CCL2 and anti-VEGFA (Bevacizumab) treatment could more effectively inhibited tumor angiogenesis and growth than single treatment did in CRCs with high expression of ETV5 (ETV5 + CRCs). Conclusions Our results not only revealed ETV5 as a novel biomarker for antiangiogenic therapy, but also indicated a potential combined therapy strategy by simultaneously targeting CCL2 and VEGFA in ETV5 + CRC.

scholarly journals Long noncoding RNA RP11-757G1.5 sponges miR-139-5p and upregulates YAP1 thereby promoting the proliferation and liver, spleen metastasis of colorectal cancer

2020 ◽  
Author(s):  
xiaojian zhu ◽  
Fanqin Bu ◽  
Ting Tan ◽  
Qilin Luo ◽  
Jingfeng Zhu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
In Situ Hybridization ◽  
Cox Regression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cox Regression Analysis

Abstract Background: Accumulating evidence indicates that long non-coding RNAs (lncRNAs) acting as crucial regulators in tumorigenesis. However, its biological functions of lncRNAs in colorectal cancer (CRC) have not been systematically clarified. Methods: An unbiased screening was performed to identify disregulated lncRNAs revealed to be implicated in CRC carcinogenesis according to an online-available data dataset. In situ hybridization (ISH), RT-qPCR and RNA fluorescence in situ hybridization (RNA-FISH) were applied to detect RP11-757G1.5 expression in CRC tissues and cell lines. The associations of RP11-757G1.5 with clinicopathological characteristics were analyzed. Their effects on prognosis were analyzed by the Kaplan-Meier analysis, Log-rank test, Univariate and Multivariate Cox regression analysis. The potential biological function of RP11-757G1.5 in CRC was investigated by Colony formation, Edu cell proliferation, Flow cytometry, Wound healing and Transwell assays. Bioinformatics binding site analysis, Luciferase reporter assay, Ago2 immunoprecipitation assays, RNA pull-down assay, RT-qPCR and Western blotting were utilized to demonstrate the mechanism of RP11-757G1.5 acts as a molecular sponge of miR-139-5p to regulate the expression of YAP1. Finally, we further explore the potential role of RP11-757G1.5 in CRC orthotopic xenografts in vivio . Results: We discovered a novel oncogenic lncRNA RP11-757G1.5, that was overexpressed in CRC tissues, especially in aggressive cases. Moreover, up-regulation of RP11-757G1.5 strongly correlated with poor clinical outcomes of patients with CRC. Functional analyses revealed that RP11-757G1.5 promoted cell proliferation in vitro and in vivo . Furthermore, RP11-757G1.5 stimulated cell migration and invasion in vitro and in vivo . Mechanistic studies illustrated that RP11-757G1.5 regulated the expression of YAP1 through sponging miR-139-5p and inhibiting its activity thereby promoting CRC progression and development. Conclusions: Altogether, these results reveal a novel RP11-757G1.5/miR-139-5p/YAP1 regulatory axis that participates in CRC carcinogenesis and progression.

scholarly journals Biological Functions and Prognostic Value of Ferroptosis-Related Genes in Bladder Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Kezhen Yi ◽  
JingChong Liu ◽  
Yuan Rong ◽  
Cheng Wang ◽  
Xuan Tang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Protein Interactions ◽  
Prognostic Value ◽  
Prognostic Model ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Prognostic Information ◽  
Cox Regression Analysis

Background: Every year, nearly 170,000 people die from bladder cancer worldwide. A major problem after transurethral resection of bladder tumor is that 40–80% of the tumors recur. Ferroptosis is a type of regulatory necrosis mediated by iron-catalyzed, excessive oxidation of polyunsaturated fatty acids. Increasing the sensitivity of tumor cells to ferroptosis is a potential treatment option for cancer. Establishing a diagnostic and prognostic model based on ferroptosis-related genes may provide guidance for the precise treatment of bladder cancer.Methods: We downloaded mRNA data in Bladder Cancer from The Cancer Genome Atlas and analyzed differentially expressed genes based on and extract ferroptosis-related genes. We identified relevant pathways and annotate the functions of ferroptosis-related DEGs using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and Gene Ontology functions. On the website of Search Tool for Retrieving Interacting Genes database (STRING), we downloaded the protein-protein interactions of DEGs, which were drawn by the Cytoscape software. Then the Cox regression analysis were performed so that the prognostic value of ferroptosis-related genes and survival time are combined to identify survival- and ferroptosis-related genes and establish a prognostic formula. Survival analysis and receiver operating characteristic curvevalidation were then performed. Risk curves and nomograms were generated for both groups to predict survival. Finally, RT-qPCR was applied to analyze gene expression.Results: Eight ferroptosis-related genes with prognostic value (ISCU, NFE2L2, MAFG, ZEB1, VDAC2, TXNIP, SCD, and JDP2) were identified. With clinical data, we established a prognostic model to provide promising diagnostic and prognostic information of bladder cancer based on the eight ferroptosis-related genes. RT-qPCR revealed the genes that were differentially expressed between normal and cancer tissues.Conclusion: This study found that the ferroptosis-related genes is associated with bladder cancer, which may serve as new target for the treatment of bladder cancer.

Impact of pharmacokinetics (PK) of sunitinib (SU) and its metabolite SU12662 on clinical outcome and toxicity in metastatic renal cell cancer (mRCC) patients.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 506-506 ◽  
Author(s):  
Nicolas Martin ◽  
Delphine Borchiellini ◽  
Julien Viotti ◽  
Emmanuel Chamorey ◽  
Gerard A. Milano ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Cox Regression ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
High Exposure ◽  
Line Setting ◽  
The Impact

506 Background: Pharmacological activity of SU is usually attributed to SU and its active metabolite SU12662, known to exhibit similar potency in inhibiting tyrosine kinase activity and cellular proliferation in vitro. However, equivalence is not clearly demonstrated towards clinical endpoints. The objective of this phase 2 study was to determine the impact of SU and SU12662 on clinical outcomes and toxicity in mRCC patients (NCT00943839). Methods: Patients with mRCC, eligible for SU in the first line setting, were prospectively included. SU was given orally at 50 mg qd for 4 weeks on/2 weeks off until progression or unacceptable toxicity. Minimal concentration at steady-state (CSSmin) was evaluated by high-performance liquid chromatography at day 28 of each cycle for both SU and SU12662. Data for tumor response, survival, and toxicity were recorded. Kaplan-Meyer’s curves with log-rank tests and cox regression models were used to identify relationships between PK parameters and survival. Chi2 tests and student t-tests were used to identify relationships with toxicity. Results: 41 patients in 7 French centers were included between 2009 and 2012. 16 patients had favourable prognosis, 13 intermediate prognosis, and 1 poor prognosis according to IMDC risk groups (Heng, J Clin Oncol 2009). Median follow-up was 30.6 months. Median progression-free survival (PFS) was 20.2 months and median overall survival (OS) was 39.5 months. Mean CSSmin for SU and SU12662 were 57.2 and 29.8 ng/ml, respectively. CSSmin of SU12662 was independently correlated to poor PFS and OS (p = 0.01 and 0.003 respectively). Patients with a mean CSSmin of SU12662 higher than 42.5 ng/ml had a worse PFS and OS compared to patients with lower concentrations: 5.7 months and 5.7 months versus 20.6 months and 39.5 months (p = 0.01 and 0.002 respectively). High CSSmin of both SU and SU12662 were associated with increased incidence of asthenia (p<0.001). Conclusions: High exposure to SU12662 was associated with poor outcomes and increased asthenia for patients with mRCC treated with SU in the first line setting. It may be related to a higher metabolism and unequal activity between SU and SU12662 in vivo. Clinical trial information: NCT00943839.

scholarly journals Overexpression of DSCR1 prevents proliferation and predicts favorable prognosis in colorectal cancer patients

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Wen-Xiang Li ◽  
Jia-Jia Zheng ◽  
Gang Zhao ◽  
Chen-Tao LYU ◽  
Wei-Qi Lu
Keyword(s):  
Cell Cycle ◽  
Overall Survival ◽  
Tumor Growth ◽  
Cox Regression ◽  
Survival Analyses ◽  
Cox Regression Analysis ◽  
Favorable Prognosis ◽  
Kaplan Meier

Abstract Objectives Down 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. Methods Firstly, 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. Results DSCR1 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. Conclusions Our 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.

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