scholarly journals High expression of HSP90 is associated with poor prognosis in patients with colorectal cancer

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7946 ◽  
Author(s):  
Shuming Zhang ◽  
Shichao Guo ◽  
Zhangfu Li ◽  
Dan Li ◽  
Qimin Zhan
Keyword(s):  
Colorectal Cancer ◽  
Poor Prognosis ◽  
Proportional Hazards ◽  
Excision Repair ◽  
Critical Role ◽  
Metabolic Process ◽  
Mrna Levels ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Hsp90 Expression

Background Heat shock protein 90 (HSP90) is a highly conserved chaperone with an approximate molecular weight of 90-kDa. It plays a critical role in maintaining stability and homeostasis of oncoproteins, helping cancer cells living in the unsuitable environmental conditions. The current study aims to inquire the difference of HSP90 expression in tumor tissues and normal tissues, analyze the correlation between HSP90 expression and the prognoses of patients with colorectal cancer (CRC), and investigate its role in CRC preliminarily. Methods Online analysis of HSP90 mRNA levels in different cancers was firstly done in Gene Expression Profiling Interactive Analysis. Then HSP90 expression was determined by immunohistochemistry between 99 CRC tissues and 81 normal tissues. Chi-square test or Fisher’s exact test was used to analyze the relationship between HSP90 and histopathologic characteristics. Kaplan–Meier analysis and Cox’s proportional hazards model were also done for further analysis of the prognostic values of HSP90. Pearson’s correlation coefficients between HSP90 expression values and other mRNA expression values were calculated based on The Cancer Genome Atlas dataset and bioinformatic analysis was done about these screened genes. Results Colorectal cancer tissues showed significantly higher expression of HSP90 than normal tissues (55.6% vs. 3.7%, P < 0.0001). Kaplan–Meier curves showed high HSP90 expression was associated with poor prognosis (P = 0.039) in CRC patients, and multivariate Cox proportional hazards regression model analysis also indicated that HSP90 expression (HR = 1.930, 95% CI [1.113–3.349], P = 0.019) linked to poor prognosis. Moreover, 85 genes were correlated with HSP90, which were involved in metabolic process and enriched in pathways of Proteasome and Base excision repair. Conclusions Our results suggested that HSP90 expression is inversely associated with survival outcomes and could be an independent prognostic factor for CRC patients. It mainly involved in metabolic process and exerted binding and catalytic activities.

scholarly journals Comprehensive analysis of ceRNA network of ERCC4 in colorectal cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12647
Author(s):  
Huixin Hu ◽  
Songyi Liu ◽  
Aining Chu ◽  
Jing Chen ◽  
Chengzhong Xing ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Regulatory Network ◽  
Drug Sensitivity ◽  
Hazard Ratio ◽  
High Expression ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Normal Tissues ◽  
Cerna Network ◽  
Kaplan Meier

Objective ERCC4 is one of the most significant molecules of Nucleotide Excision Repair (NER), which has been researched due to its high expression in colorectal cancer (CRC). This study aimed to find out the ceRNA (competitive endogenous RNA) network of ERCC4 in CRC. Methods and Materials Pan cancer mRNA expression of ERCC4 was evaluated using TCGA database. The protein expression of ERCC4 was evaluated based on the Human Protein Atlas (HPA). We screened DElncRNAs and DEmiRNAs in two groups of ERCC4high and ERCC4low expression in CRC. Then a lncRNA-miRNA-ERCC4 regulatory network was constructed based on DElncRNAs and DEmiRNAs using Starbase database and visualized by Cytoscape software. Kaplan-Meier analysis was performed to evaluate the prognostic value of the ceRNA network. Further, RT-PCR was performed to validate the expression of the representative molecules in the ceRNA network in CRC and normal tissues. The relationship between drug sensitivity and these molecules were also evaluated using RNAactDrug database. Results ERCC4 was overexpressed in a variety of tumors at mRNA levels, including CRC. High expression of ERCC4 was also observed on protein level in CRC. A total of 1,885 DElncRNAs and 68 DEmiRNAs were identified from CRC samples in ERCC4high and ERCC4low expression groups. Predicted by the Starbase database, we got interacting miRNAs and lncRNAs of ERCC4 from the DEmiRNAs and DElncRNAs, and a lncRNA-miRNA-ERCC4 regulatory network was constructed. Kaplan-Meier survival curves results showed that miR-200c-3p (hazard ratio [HR] = 0.62, P = 0.032), MALAT1 (HR = 1.54, P = 0.016), and AC005520.2 (hazard ratio [HR] = 1.75, P = 0.002) were significantly associated with the prognosis of CRC. After validation by RT-PCR, we found that ERCC4 and MALAT1 were up-regulated in CRC compared with normal tissues, while miR-200c-3p was down-regulated. A strong negative correlation was observed between MALAT1 and miR-200c-3p. Drug sensitivity analysis showed that ERCC4, miR-200c and MALAT1 were all associated with Cisplatin. Conclusion We constructed a ceRNA network of ERCC4 in CRC, of which the MALAT1-miR-200c-3p-ERCC4 axis may be involved in the development, prognosis and chemotherapy sensitivity of CRC. These findings might provide novel clues and insights on the molecular mechanisms of ERCC4 and NER pathway in CRC.

Delta-like ligand 4 level in colorectal cancer is associated with tumor aggressiveness, body mass index and clinical outcome

2021 ◽  
pp. 1-8
Author(s):  
Zixi Zhang ◽  
Xiao Li ◽  
Xueli Yan ◽  
He Qiu ◽  
Gai Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Body Mass Index ◽  
Body Mass ◽  
Proportional Hazards ◽  
Prognostic Indicator ◽  
Clinicopathological Characteristics ◽  
Cox Proportional Hazards ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Numerous Cell

BACKGROUND: The Notch signaling regulates numerous cell growth, differentiation, and death. However, the expression pattern of its ligand Delta-like 4 (DLL4) in tumors is still uncertain. OBJECTIVE: In the present study, we examined DLL4 expression in colorectal cancer as well as assessed its role as a prognostic indicator in the present study. Methods: DLL4 expression was examined by immunohistochemistry in 265 surgically resected specimens of colorectal cancer and adjacent normal tissues. The relationship between DLL4 expression and clinicopathological characteristics was analyzed. The association of DLL4 expression with the patients’ overall survival rate was assessed by Kaplan-Meier and Cox proportional-hazards regression. RESULTS: Increased DLL4 level was detected in colorectal cancer compared with that of normal tissues. Elevated DLL4 level in colorectal cancer was associated with increased body mass index of patients. Moreover, increased DLL4 level was also found to be correlated with tumor invasion, metastases and unfavorable clinical outcom of patients. CONCLUSIONS: DLL4 level is increased in colorectal cancer, especially in patients with increased body mass index, indicating potential involvement of obesity-related tumorigenesis and development. It might also serve as a novel molecular marker to predicate outcome of patients.

scholarly journals Cyclin-Dependent Kinase Regulatory Subunit 2 Indicated Poor Prognosis and Facilitated Aggressive Phenotype of Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Jie Zhang ◽  
Qianqian Song ◽  
Jinxia Liu ◽  
Lina Lu ◽  
Yuqing Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Disease Free Survival ◽  
Normal Liver ◽  
Regulatory Subunit ◽  
Mrna Levels ◽  
Cyclin Dependent Kinase ◽  
Normal Tissues ◽  
Hcc Cells

Cyclin-dependent kinase regulatory subunit 2 (CKS2) is a member of the cell cycle-dependent protein kinase subunit family, which is implicated as an oncogene in various malignancies. However, the clinical significance, oncogenic functions, and related mechanisms of CKS2 in hepatocellular carcinoma (HCC) remain largely unclear. In the present study, expression features and prognostic value of CKS2 were evaluated in the bioinformatic databases and HCC tissues. The effects of CKS2 on the malignant phenotypes of HCC cells were explored in vitro. According to the analyses of three bioinformatic databases, mRNA levels of CKS2 were elevated in HCC tissues compared with the normal tissues. Immunohistochemical assays found that high CKS2 expression was closely associated with liver cirrhosis (P=0.019), poor differentiation (P=0.02), portal vein invasion (P<0.001), TNM stage (P=0.019), tumor metastasis (P=0.008), and recurrence (P=0.003). The multivariate regression analyses suggested that CKS2 was an independent prognostic factor for overall survival (HR=2.088, P=0.014) and disease-free survival (HR=2.511, P=0.002) of HCC patients. Moreover, the bioinformatic analyses indicated that CKS2 might be associated with the malignant phenotypes in HCC progression. In addition, in vitro assays showed that CKS2 expression was higher in HCC cell lines than in normal liver cells. Knockdown of CKS2 remarkably repressed the proliferation, colony formation (P=0.0003), chemoresistance, migration (P=0.0047), and invasion (P=0.0012) of HCC cells. Taken together, overexpression of CKS2 was significantly correlated with poor prognosis of HCC patients and the malignant phenotypes of HCC cells, suggesting that it was a novel prognostic biomarker and potential target of HCC.

The Effect of High CDC6 Levels on Predicting Poor Prognosis in Colorectal Cancer

Chemotherapy ◽  
2022 ◽  
pp. 1-10
Author(s):  
Cheng Yang ◽  
Na Xie ◽  
Zhifei Luo ◽  
Xiling Ruan ◽  
Yixin Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Poor Prognosis ◽  
Cancer Metastasis ◽  
Mrna Level ◽  
Normal Mucosa ◽  
Tnm Stage ◽  
Expression Levels ◽  
Normal Tissues

<b><i>Introduction:</i></b> We investigated the function of cell division cycle 6 (CDC6) on the prognosis in colorectal carcinoma (CRC). <b><i>Methods:</i></b> CDC6 protein expression levels in 121 patients with colorectal cancer and adjacent normal mucosa were detected by immunohistochemistry. <b><i>Results:</i></b> Compared to adjacent normal tissues, CDC6 mRNA level was overexpressed in CRC tissues. Moreover, CDC6 protein levels were expressed up to 93.39% (113/121) in CRC tissues in the cell nucleus or cytoplasm. However, there were only 5.79% (7/121) in normal mucosal tissues with nuclear expression. CDC6 expression was significantly correlated with TNM stage and tumor metastasis. The 5-year survival rate was lower in the high CDC6 expression group than the low group. After silencing of CDC6 expression in SW620 cells, cell proliferation was slowed, the tumor clones were decreased, and the cell cycle was arrested in G1 phase. In multivariate analysis, increased CDC6 protein expression levels in colon cancer tissues were associated with cancer metastasis, TNM stage, and patient survival time. <b><i>Conclusion:</i></b> CDC6 is highly expressed in CRC, and downregulation of CDC6 can slow the growth of CRC cells in vitro. It is also an independent predictor for poor prognosis and may be a useful biomarker for targeted therapy and prognostic evaluation.

Prognostic value of biglycan in gastric cancer

2020 ◽  
Author(s):  
Sizhe Hu ◽  
Peipei Li ◽  
Chenying Wang ◽  
Xiyong Liu
Keyword(s):  
Gastric Cancer ◽  
Transcription Factors ◽  
Poor Prognosis ◽  
Prognostic Significance ◽  
Bioinformatic Analysis ◽  
Gene Set Enrichment Analysis ◽  
High Expression ◽  
Mrna Levels ◽  
Gene Signatures ◽  
Kaplan Meier

Abstract Background: BGN (biglycan) is a family member of small leucine-rich repeat proteoglycans. High expression of BGN might enhance the invasion and metastasis in some types of tumors. Here, the prognostic significance of BGN was evaluated in gastric cancer.Material and Methods: Two independent Gene Expression Omnibus (GEO) gastric cancer microarray datasets( n= 64, n=432) were collected for this study. Kaplan-Meier analysis was applied to evaluate if BGN impacts the outcomes of gastric cancer. The gene set enrichment analysis (GSEA) was used to explore BGN and cancer-related gene signatures. Bioinformatic analysis predicted the putative transcription factors of BGN.Results: For gastric cancer, the mRNA expression level of BGN in tumor tissues was significantly higher than that in normal tissues. Kaplan-Meier analysis showed that higher expression of BGN mRNA was significantly associated with more reduced recurrence-free survival (RFS). GSEA results suggested that BGN significantly enriched metastasis and poor prognosis gene signatures, revealing that BGN might be associated with cell proliferation, poor differentiation, high invasiveness of gastric cancer. Meanwhile, the putative transcription factors, including AR, E2F1, and TCF4, weres predicted by bioinformatic analysis and also significantly correlated with expression of BGN in mRNA levels. Conclusion: High expression of BGN mRNA was significantly related to poor prognosis, which suggested BGN was a potential prognostic biomarker and therapeutic target of gastric cancer.

scholarly journals A Functional Polymorphism in the Promoter Region of Interleukin-12B Increases the Risk of Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Yabin Liu ◽  
Binghui Li ◽  
Lili Wang ◽  
Dexian Kong
Keyword(s):  
Colorectal Cancer ◽  
Direct Sequencing ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Normal Tissues ◽  
Sequencing Method ◽  
Direct Sequencing Method ◽  
Healthy Control ◽  
Polymerase Chain ◽  
Interleukin 12B

Objective. To investigate whether the polymorphisms of interleukin-12B (IL-12B) were associated with the risk of developing colorectal cancer (CRC). Patients and Methods. Genotypes of rs17860508 and rs3212227 were determined by polymerase chain reaction with a direct sequencing method in 329 CRC patients and 342 matched healthy control subjects. The expression of IL-12B mRNA was determined by RT-qPCR in 50 pairs of CRC tissues and their adjacent normal tissues. Results. Compared with TTAGAG/TTAGAG genotype of rs17860508, the GC/GC and TTAGAG/GC genotypes may significantly increase the risk of CRC (OR = 1.81, 95% CI = 1.18–2.78; OR = 1.46, 95% CI = 1.01–2.12, respectively). Furthermore, the mRNA levels of IL-12B were significantly higher in the CRC tissues from patients with the rs17860508 GC/GC genotype than those with the TTAGAG/GC (P=0.009) and TTAGAG/TTAGAG (P=0.001) genotypes. Conclusion. These data suggested that the rs17860508 GC/GC genotype might upregulate IL-12B expression at the transcriptional level and thus increase the risk of CRC.

scholarly journals Overexpression of IQGAP1 in advanced colorectal cancer correlates with poor prognosis-critical role in tumor invasion

2010 ◽  
pp. NA-NA ◽  
Author(s):  
Hiroyuki Hayashi ◽  
Kazuki Nabeshima ◽  
Mikiko Aoki ◽  
Makoto Hamasaki ◽  
Sotaro Enatsu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Invasion ◽  
Poor Prognosis ◽  
Advanced Colorectal Cancer ◽  
Critical Role

scholarly journals KIF20A Predicts Poor Survival of Patients and Promotes Colorectal Cancer Tumor Progression through the JAK/STAT3 Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Qi Zhang ◽  
Jun Di ◽  
Zhiyu Ji ◽  
Aoning Mi ◽  
Quanying Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Progression ◽  
Cox Regression ◽  
Critical Role ◽  
Depth Of Invasion ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Reduce Cell Proliferation ◽  
Cancer Tumor ◽  
And Migration

Kinesin family member 20A (KIF20A) has been recently reported to be upregulated and associated with increased invasiveness and metastasis in several malignancies. However, the role of KIF20A in colorectal cancer (CRC) is still unclear. This study is aimed at investigating the potential roles of KIF20A in the development of CRC. The results of bioinformatics analysis, immunohistochemical staining, and Western blot analysis showed that KIF20A was overexpressed in CRC tissues compared with adjacent normal tissues. High expression of KIF20A in CRC tissues was associated with depth of invasion, lymphatic node metastasis, distant metastasis, and TNM stage. Moreover, the Kaplan-Meier survival analysis showed that CRC patients with high KIF20A expression had poor prognoses. Cox regression analysis revealed that KIF20A was an independent prognostic factor in patients with CRC. Further studies suggested that knockdown of KIF20A was able to reduce cell proliferation and migration by inhibiting the JAK/STAT3 pathway. Taken together, we propose that KIF20A plays a critical role in the tumorigenesis and tumor progression of colorectal cancer and could represent a potential therapeutic target for CRC.

scholarly journals Lycopene Protects against Smoking-Induced Lung Cancer by Inducing Base Excision Repair

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 643 ◽  
Author(s):  
Junrui Cheng ◽  
Baxter Miller ◽  
Emilio Balbuena ◽  
Abdulkerim Eroglu
Keyword(s):  
Oxidative Stress ◽  
Lung Cancer ◽  
Cigarette Smoke ◽  
Connexin 43 ◽  
Excision Repair ◽  
Critical Role ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Cigarette Smoke Exposure ◽  
Mrna Levels

Background: Oxidative stress plays a critical role in lung cancer progression. Carotenoids are efficient antioxidants. The objective of this study was to explore the efficacy of all-trans retinoic acid (ATRA) and carotenoids in cigarette smoke-induced oxidative stress within A549 human lung cancer epithelial cells. Methods: A549 cells were pretreated with 1-nM, 10-nM, 100-nM, 1-μM and 10-μM ATRA, β-carotene (BC) and lycopene for 24 h, followed by exposure to cigarette smoke using a smoking chamber. Results: The OxyBlot analysis showed that smoking significantly increased oxidative stress, which was inhibited by lycopene at 1 nM and 10 nM (p < 0.05). In the cells exposed to smoke, lycopene increased 8-oxoguanine DNA glycosylase (OGG1) expression at 1 nM, 10 nM, 100 nM, and 1 μM (p < 0.05), but not at 10 μM. Lycopene at lower doses also improved Nei like DNA glycosylases (NEIL1, NEIL2, NEIL3), and connexin-43 (Cx43) protein levels (p < 0.05). Interestingly, lycopene at lower concentrations promoted OGG1 expression within the cells exposed to smoke to an even greater extent than the cells not exposed to smoke (p < 0.01). This may be attributed to the increased SR-B1 mRNA levels with cigarette smoke exposure (p < 0.05). Conclusions: Lycopene treatment at a lower dosage could inhibit smoke-induced oxidative stress and promote genome stability. These novel findings will shed light on the molecular mechanism of lycopene action against lung cancer.

Identification of epigenetic silencing of GCNT2 expression by comprehensive real-time PCR screening in colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 506-506
Author(s):  
Kazunorii Nakamura ◽  
Horomichi Sawaki ◽  
Keishi Yamashita ◽  
Masahiko Watanabe ◽  
Hisashi Narimatsu
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Real Time ◽  
Cell Lines ◽  
Real Time Pcr ◽  
Critical Role ◽  
Normal Mucosa ◽  
Primary Cancer ◽  
Normal Tissues ◽  
Cancer Tissues

506 Background: Glycoprotein expression profile has been proved to be dramatically altered in human cancers, however specific glycogenes which are aberrant in expression in cancer cells has not been fully identified. Recent accumulated evidence supported notion that the reduced expression of tumor suppressor genes is explained by DNA promoter methylation in human cancer. Methods: We used Comprehensive Real time PCR system (CRPS) for glycogenes (189 genes) to identify genes aberrantly expressed in colorectal cancer tissues (CRC) as compared to the corresponding normal mucosa tissues. GCNT2 was of particular interest among the identified genes in CRC. Results: (1) GCNT2 harbors 3 isoforms which have different promoter regions. (2) All of the 3 isoforms of GCNT2 genes were remarkably decreased in CRC as compared to the corresponding normal mucosa, and each isoform expression was strongly associated with other 2 isoforms in primary cancer tissues by TaqMan real time PCR (R = 0.99-995, p < 0.0001). (3) Among the 5 CRC cell lines (DLD1, HCT116, CACO2, LOVO), those which were silenced in expression were reactivated by demethylating agents such as 5-aza-2’ deoxycytidine and trichostatin A. (4) Promoter region of the variant 2 of GCNT2 was consistent with its silenced expression in CRC cell lines by cloned sequence, so we examined DNA methylation status of the promoter of the GCNT2 variant 2 in 50 primary cancer tissues and the corresponding normal tissues. Quantitative MSP revealed that almost half of normal tissues have methylation as high as tumor tissues, while, in the primary CRC with less methylation in the corresponding normal tissues, DNA methylation was higher in primary CRC tissues than in the corresponding normal tissues. Finally, GCNT2 variant 2 stable transfection induced expression of other 2 isoform variants. Conclusions: We identified novel methylation gene GCNT2 among the glycoenes. Glycoenes that were altered in genomic or epigenetic manner have been few, so GCNT2 may play a critical role in cancer progression through glycan change.

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