Clinical Significance and Prognostic Value of miR-28-5p in Colon Cancer

Background. The association of miR-28-5p with colon cancer remains to be elucidated. This study aimed to determine the clinical significance and prognostic value of miR-28-5p in colon cancer. Methods. We retrospectively analyzed the data of miR-28-5p in colon adenocarcinoma data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and the data was divided into cancer group and normal group, respectively. Forty colon cancer tissues and adjacent normal tissues were collected and tested by qRT-PCR methods. The difference of the miR-28-5p expression between colon cancer and normal tissues was compared. The clinical significance of miR-28-5p in colon cancer and the association with the survival were determined. The predictive value of miR-28-5p in clinical features was determined using receiver operating characteristic curve. The target genes of miR-28-5p were identified, and the functional of target genes was performed using bioinformatics analysis. Results: The expression of miR-28-5p was increased in colon cancer tissues compared with normal controls (p=0.037). The expression of miR-28-5p was significantly increased in tissues with distant metastases compared with that without distant metastases (p=0.026). Patients with high expression of miR-28-5p have a shorter survival time than those with low expression (p=0.004). Cox analysis showed that miR-28-5p was an independent predictor for the survival of patients (p=0.014). Combination of miR-28-5p with TNM stage and clinical stage can improve the prognostic value for the patients (p<0.05). miR-28-5p has a moderate predictive value in predicting the TNM stage and clinical stage (T stage: AUC=0.515; N stage: AUC=0.523, M stage: AUC=0.572; clinical stage: AUC=0.539). 711 potential target genes of miR-28-5p were screened; their function and pathways were identified. Conclusions: This study demonstrated that miR-28-5p was increased in colon cancer and can be an independent indicator for the overall survival in patients with colon cancer.

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The Clinical Significance and Prognostic Value of HER2 Expression in Bladder Cancer: a Systematic Review and Meta-analysis

10.21203/rs.3.rs-135089/v1 ◽

2020 ◽

Author(s):

Kai Gan ◽

Yue Gao ◽

KuangZheng Liu ◽

Bin Xu ◽

Ming Chen

Keyword(s):

Bladder Cancer ◽

Clinical Significance ◽

Prognostic Value ◽

Meta Analysis ◽

Growth Factor Receptor ◽

Tumor Stage ◽

The Cancer Genome Atlas ◽

Her2 Expression ◽

Large Tumor ◽

Normal Tissues

Abstract Objective: Human Epidermal Growth Factor Receptor 2 (HER2) is highly expressed in a variety of tumors and associated with patients’ prognosis, but its role in bladder cancer remains unclear. We conducted this meta-analysis to explore the clinical significance and prognostic value of HER2 in bladder cancer and its potentiality as an immunotherapy target.Methods: PubMed was searched for studies published between January 1, 2000 and January 1, 2020. The odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were used to investigate the relationship between HER2 and bladder cancer. UALCAN website was used to obtain TCGA (The cancer genome atlas) database.Results: Our study includes 14 articles, 1398 patients. HER2 expression was significantly higher in bladder cancer than in normal tissues. Our meta-analysis results did not reveal any effect of gender on the expression of HER2 levels in bladder cancer patients. However, HER2 expression in male patients was significantly higher than that in women according to TCGA databases. HER2 expression was also associated with carcinoma in situ, multifocal tumors, large tumor size, high tumor stage and grade, lymph node metastases, risk of recurrence and progression, low recurrence-free survival (RFS) rate. HER2 expression status had no effect on overall survival.Conclusions: Our meta-analysis showed that HER2 expression was related to pathological malignancy and poor prognosis in bladder cancer which indicated that it could be used as an effective biomarker and therapeutic target.

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The expression and clinical significance of PDCD4 and Her-2 in human gastric cancer

European Journal of Inflammation ◽

10.1177/2058739219828236 ◽

2019 ◽

Vol 17 ◽

pp. 205873921982823

Author(s):

Yuelou Yang ◽

Xiangjun Jiang ◽

Dong Li ◽

Feiyan Wang ◽

Qun Yang ◽

...

Keyword(s):

Gastric Cancer ◽

Protein Expression ◽

Western Blot ◽

Clinical Significance ◽

Normal Mucosa ◽

Normal Tissues ◽

Positive Rate ◽

Her 2 ◽

Cancer Tissues ◽

Pdcd4 Protein

To investigate the correlation and clinical significance between programmed cell death factor 4 (PDCD4) and epidermal growth factor receptor 2 (Her-2) expressions and clinicopathological parameters in patients with gastric cancer, a total of 65 cases of gastric cancer and the corresponding normal mucosa with PDCD4 and Her-2 protein expressions were detected by SP immunohistochemical staining, and 50 cases of gastric cancer and the corresponding normal mucosa with PDCD4 and Her-2 protein expression quantities were detected by Western blot, in order to analyze the relationship between the positive expressions of PDCD4 and Her-2 protein and the clinicopathological features of patients with gastric cancer. The results showed that the positive rate of PDCD4 protein expression in gastric cancer tissues was 7.7%, which was significantly lower than that in the corresponding normal tissues, that is, 77.5% ( P < 0.05); the positive rate of Her-2 expression was 41.5%, which was significantly higher than that of the corresponding normal tissues, which is 2.5% ( P < 0.05). The Western blot test showed that the expression of PDCD4 protein in gastric cancer was 0.3105 ± 0.0073, which was significantly lower than that in the corresponding normal tissues, that is, 0.9428 ± 0.0127 ( P < 0.05); the expression level of Her-2 protein in gastric cancer tissues was 0.9428 ± 0.0127, which was significantly higher than that of the corresponding normal mucosa, which is 0.2054 ± 0.0264 ( P < 0.05). The positive expressions of PDCD4 (5/65) and Her-2 (27/65) were significantly correlated with the differentiation degrees and TNM stages of gastric cancer ( P < 0.05). However, no significant correlation can be observed from Table 2 ( P > 0.05), regarding sex, age, tumor size, and lymph node metastasis. Our research claimed that PDCD4 and Her-2 may play an important role in the invasion and metastasis of gastric cancer, which has a negative correlation with biological behaviors of gastric cancer. The low expression of PDCD4 and the high expression of Her-2 in gastric cancer may promote the occurrence and progression of cancer. The PDCD4 and Her-2 test can be used as an index to evaluate the malignant biological behaviors of gastric cancer and prognosis, and provide a theoretical basis for targeted therapy.

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The Differential Expression of Core Genes in Nucleotide Excision Repair Pathway Indicates Colorectal Carcinogenesis and Prognosis

BioMed Research International ◽

10.1155/2018/9651320 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Jingwei Liu ◽

Hao Li ◽

Liping Sun ◽

Xue Feng ◽

Zhenning Wang ◽

...

Keyword(s):

Rectal Cancer ◽

Colon Cancer ◽

Nucleotide Excision Repair ◽

Excision Repair ◽

Tnm Stage ◽

Colorectal Carcinogenesis ◽

Clinicopathological Parameters ◽

Normal Tissues ◽

T Stage ◽

Nucleotide Excision

Background. Nucleotide excision repair (NER) plays a critical role in maintaining genome integrity. This study aimed to investigate the expression of NER genes and their associations with colorectal cancer (CRC) development. Method. Expressions of NER genes in CRC and normal tissues were analysed by ONCOMINE. The Cancer Genome Atlas (TCGA) data were downloaded to explore relationship of NER expression with clinicopathological parameters and survival of CRC. Results. ERCC1, ERCC2, ERCC5, and DDB2 were upregulated while ERCC4 was downregulated in CRC. For colon cancer, high ERCC3 expression was related to better T stage; ERCC5 expression indicated deeper T stage and distant metastasis; DDB2 expression suggested earlier TNM stage. For rectal cancer, ERCC2 expression correlated with favourable T stage; XPA expression predicted worse TNM stage. ERCC2 expression was associated with worse overall survival (OS) in colon cancer (HR=1.53, P=0.043). Colon cancer patients with high ERCC4 expression showed favorable OS in males (HR=0.54, P=0.035). High XPC expression demonstrated decreased death hazards in rectal cancer (HR=0.40, P=0.026). Conclusion. ERCC1, ERCC2, ERCC4, ERCC5, and DDB2 were differently expressed in CRC and normal tissues; ERCC2, ERCC3, ERCC5, XPA, and DDB2 correlated with clinicopathological parameters of CRC, while ERCC2, ERCC4, and XPC might predict CRC prognosis.

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The expression and Clinical Significance of miRNA-135a and Bach1 in colorectal cancer

International Surgery ◽

10.9738/intsurg-d-20-00026.1 ◽

2021 ◽

Author(s):

Yang zhi Jiang ◽

Qing Guo Tao ◽

fei yan Zhu

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Clinical Information ◽

Control Group ◽

Tumor Control ◽

Cancer Tissue ◽

Expression Levels ◽

Real Time Quantitative Pcr ◽

Normal Tissues ◽

Cancer Tissues

BACKGROUND AIM To explore the correlation between the expression of miRNA-135a and Bach1 in colorectal cancer tissue and the patient's clinical information. Methods 60 patients with colorectal carcinoma were treated as a control group. Real-time quantitative PCR assays and immunohistochemistry method were performed to detect the expression of miRNA-135a and Bach1 in 60 colorectal carcinomas and adjacent normal tissues, and the clinical and pathological classifications had also been investigated. The SPSS 19.00 software was used. All data represented mean±SD of three independent experiments. P<0.05 was considered statistically significant. Results miRNA-135a expression levels increased significantly in the colon cancer tissues compared with the non-tumor control tissues(P<0.01). miRNA-135a expression levels were higher in stage III/IV than in stage I/II colon cancer patients. The expression level of Bach1 in colorectal cancer was significantly lower(P<0.01). Bach1 and miRNA-135a were negatively correlated. Conclusions: The levels of miRNA-135a and Bach1 were opposite, the over-expression of miRNA-135a might downregulated the expression of Bach1, which might be involved in the pathogenesis of colorectal cancer.

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Expression of PAWR predicts prognosis of ovarian cancer

Cancer Cell International ◽

10.1186/s12935-020-01704-y ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Jiahong Tan ◽

Kangjia Tao ◽

Xu Zheng ◽

Dan Liu ◽

Ding Ma ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Prognostic Value ◽

Interaction Network ◽

Clinical Samples ◽

Normal Tissues ◽

Cancer Management ◽

Disease Associations ◽

Drug Responsiveness ◽

Cancer Tissues

Abstract Background Ovarian cancer greatly threatens the general health of women worldwide. Implementation of predictive prognostic biomarkers aids in ovarian cancer management. Methods Using online databases, the general expression profile, target-disease associations, and interaction network of PAWR were explored. To identify the role of PAWR in ovarian cancer, gene correlation analysis, survival analysis, and combined analysis of drug responsiveness and PAWR expression were performed. The predictive prognostic value of PAWR was further validated in clinical samples. Results PAWR was widely expressed in normal and cancer tissues, with decreased expression in ovarian cancer tissues compared with normal tissues. PAWR was associated with various cancers including ovarian cancer. PAWR formed a regulatory network with a group of proteins and correlated with several genes, which were both implicated in ovarian cancer and drug responsiveness. High PAWR expression denoted better survival in ovarian cancer patients (OS: HR = 0.84, P = 0.0077; PFS, HR = 0.86, P = 0.049). Expression of PAWR could predict platinum responsiveness in ovarian cancer and there was a positive correlation between PAWR gene effect and paclitaxel sensitivity. In 12 paired clinical samples, the cancerous tissues exhibited significantly lower PAWR expression than matched normal fallopian tubes. The predictive prognostic value of PAWR was maintained in a cohort of 50 ovarian cancer patients. Conclusions High PAWR expression indicated better survival and higher drug responsiveness in ovarian cancer patients. PAWR could be exploited as a predictive prognostic biomarker in ovarian cancer.

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ChrXq27.3 miRNA cluster functions in cancer development

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01910-0 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Kosuke Yoshida ◽

Akira Yokoi ◽

Yusuke Yamamoto ◽

Hiroaki Kajiyama

Keyword(s):

Cancer Progression ◽

Target Genes ◽

Epithelial Mesenchymal Transition ◽

Mature Mirnas ◽

Mirna Cluster ◽

Mesenchymal Transition ◽

Normal Tissues ◽

Mirna Clusters ◽

Cancer Tissues ◽

Encoding Genes

AbstractMicroRNAs (miRNAs) regulate the expression of their target genes post-transcriptionally; thus, they are deeply involved in fundamental biological processes. miRNA clusters contain two or more miRNA-encoding genes, and these miRNAs are usually coexpressed due to common expression mechanisms. Therefore, miRNA clusters are effective modulators of biological pathways by the members coordinately regulating their multiple target genes, and an miRNA cluster located on the X chromosome q27.3 region has received much attention in cancer research recently. In this review, we discuss the novel findings of the chrXq27.3 miRNA cluster in various types of cancer.The chrXq27.3 miRNA cluster contains 30 mature miRNAs synthesized from 22 miRNA-encoding genes in an ~ 1.3-Mb region. The expressions of these miRNAs are usually negligible in many normal tissues, with the male reproductive system being an exception. In cancer tissues, each miRNA is dysregulated, compared with in adjacent normal tissues. The miRNA-encoding genes are not uniformly distributed in the region, and they are further divided into two groups (the miR-506-514 and miR-888-892 groups) according to their location on the genome. Most of the miRNAs in the former group are tumor-suppressive miRNAs that are further downregulated in various cancers compared with normal tissues. miR-506-3p in particular is the most well-known miRNA in this cluster, and it has various tumor-suppressive functions associated with the epithelial–mesenchymal transition, proliferation, and drug resistance. Moreover, other miRNAs, such as miR-508-3p and miR-509-3p, have similar tumor-suppressive effects. Hence, the expression of these miRNAs is clinically favorable as prognostic factors in various cancers. However, the functions of the latter group are less understood. In the latter group, miR-888-5p displays oncogenic functions, whereas miR-892b is tumor suppressive. Therefore, the functions of the miR-888–892 group are considered to be cell type- or tissue-specific.In conclusion, the chrXq27.3 miRNA cluster is a critical regulator of cancer progression, and the miRNAs themselves, their regulatory mechanisms, and their target genes might be promising therapeutic targets.

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Construction of a long noncoding RNA-based competing endogenous RNA network and prognostic signatures of left- and right-side colon cancer

Cancer Cell International ◽

10.1186/s12935-021-01901-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ke-zhi Li ◽

Yi-xin Yin ◽

Yan-ping Tang ◽

Long Long ◽

Ming-zhi Xie ◽

...

Keyword(s):

Colon Cancer ◽

Prognostic Value ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Molecular Characteristics ◽

Prognostic Signature ◽

Cerna Network ◽

Colon Cancers ◽

Cancer Tissues

Abstract Background Cancers located on the right and left sides of the colon have distinct clinical and molecular characteristics. This study aimed to explore the regulatory mechanisms of location-specific long noncoding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) in colon cancer and identify potential prognostic biomarkers. Method Differentially expressed lncRNAs (DELs), miRNAs (DEMs), and genes (DEGs) between right- and left-side colon cancers were identified by comparing RNA sequencing profiles. Functional enrichment analysis was performed for the DEGs, and a ceRNA network was constructed. Associations between DELs and patient survival were examined, and a DEL-based signature was constructed to examine the prognostic value of these differences. Clinical colon cancer tissues and Gene Expression Omnibus (GEO) datasets were used to validate the results. Results We identified 376 DELs, 35 DEMs, and 805 DEGs between right- and left-side colon cancers. The functional enrichment analysis revealed the functions and pathway involvement of DEGs. A ceRNA network was constructed based on 95 DEL–DEM–DEG interactions. Three DELs (LINC01555, AC015712, and FZD10-AS1) were associated with the overall survival of patients with colon cancer, and a prognostic signature was established based on these three DELs. High risk scores for this signature indicated poor survival, suggesting that the signature has prognostic value for colon cancer. Examination of clinical colon cancer tissues and GEO dataset analysis confirmed the results. Conclusion The ceRNA regulatory network suggests roles for location-specific lncRNAs in colon cancer and allowed the development of an lncRNA-based prognostic signature, which could be used to assess prognosis and determine treatment strategies in patients with colon cancer.

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Clinical Significance of MicroRNA-155 Regulated Autophagy and Apoptosis by targeting gene Rictor/Fos in Gastric Cancer Progression

10.21203/rs.3.rs-18875/v2 ◽

2020 ◽

Author(s):

Gang Chen ◽

Yu Li ◽

Zhijian Ren ◽

Yanmei Gu ◽

Futian Tang ◽

...

Keyword(s):

Gastric Cancer ◽

Western Blot ◽

Cancer Progression ◽

Target Genes ◽

Clinical Stage ◽

Expression Level ◽

Apoptosis Pathway ◽

Significant Difference ◽

Cancer Tissues ◽

Low Expression

Abstract BACKGROUND Microrna-155 plays an important role in the pathogenesis, progression and treatment of various cancers. It is abnormally expressed in gastric cancer, but its expression level, mechanism and significance are controversial in different studies. So we make the study to explore the expression level, significance and mechanism of microRNA-155 on gastric cancer. METHODS Target genes of microRNA-155 in TargetScan and mirDB databases were analyzed by Wayne Mapping, Enrichr database, String database, TIMER database. Forty-three pairs of cancer tissues and adjacent tissues were collected to extract total RNA and protein. Expression of MicroRNA-155, Rictor, Fos, Beclin1, LC3, caspase3 and caspase9 were measured by qRT-PCR and western blot. The relationship between gene expression and clinicopathological factors were analyzed. SPSS 23.0 was used for statistical analysis. RESULTS A total of 700 (miRDB) and 556 (TargetScan) target genes were obtained and 280 genes were in the intersection of Wayne Mapping, 49 of them had a target score of 90 or more. GO and KEGG analysis revealed that they were related to autophagy or apoptosis pathway. Rictor and Fos were selected as research objects. Thirty-two cases showed high microRNA-155 expression (group H) and 11 cases showed low expression (group L). Twelve patients had high Rictor expression and 31 patients had low expression; Thirteen cases had roughly normal Fos expression and 30 cases had low or negative expression; Thirty-three cases had high Beclin1/LC3 expression and 10 cases had low expression; Ten cases had high caspase3/caspase9 expression and 33 cases had low expression. According to the results of immunohistochemistry and western blot, Rictor, Fos, caspase3 and caspase9 were low expressed while Beclin1 and LC3 were high expressed in group H. However, all the six genes had no significant difference in group L. CONCLUSIONS The abnormal expression of microRNA-155 may indicate the occurrence of gastric cancer and its expression level is negatively correlated with clinical stage of cancer. The down-regulated expression of Rictor and Fos, enhancement of autophagy and weakening of apoptosis may be related to the over-expression of microRNA-155. MicroRNA-155 may promote the progression of gastric cancer by promoting autophagy and inhibiting apoptosis.

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The E2F family as potential biomarkers and therapeutic targets in colon cancer

PeerJ ◽

10.7717/peerj.8562 ◽

2020 ◽

Vol 8 ◽

pp. e8562 ◽

Cited By ~ 3

Author(s):

Haibo Yao ◽

Fang Lu ◽

Yanfei Shao

Keyword(s):

Colon Cancer ◽

Overall Survival ◽

Disease Free Survival ◽

Expression Levels ◽

Protein Levels ◽

Normal Tissues ◽

Significant Difference ◽

Regulation Of Cell Cycle ◽

Cancer Tissues ◽

Potential Biomarkers

Background The E2F family is a group of genes encoding a series of transcription factors in higher eukaryotes and participating in the regulation of cell cycle and DNA synthesis in mammals. This study was designed to investigate the role of E2F family in colon cancer. Methods In this study, the transcriptional levels of E2F1-8 in patients with colon cancer from GEPIA was examined. Meanwhile, the immunohistochemical data of the eight genes were also obtained in the The Human Protein Atlas website. Additionally, we re-identified the mRNA expression levels of these genes via real time PCR. Furthermore, the association between the levels of E2F family and stage plot as wells overall survival of patients with colon cancer were analyzed. Results We found that the mRNA and protein levels of E2F1, E2F2, E3F3, E2F5, E2F7 and E2F8 were significantly higher in colon cancer tissues than in normal colon tissues while the expression levels of E2F4 and E2F6 displayed no significant difference between colon cancer tissues and normal tissues. Additionally, E2F3, E2F4, E2F7 and E2F8 were significantly associated with the stages of colon cancer. The Kaplan-Meier Plotter showed that the high levels of E2F3 conferred a worse overall survival and disease free survival of patients with colon cancer. Also, high levels of E2F4 resulted in a worse overall survival. Conclusion Our study implied that E2F3, E2F4, E2F7 and E2F8 are potential targets of precision therapy for patients with colon cancer while E2F1, E2F2, E3F3, E2F5, E2F7 and E2F8 are potential biomarkers for the diagnosis of colon cancer.

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Prognostic value of microRNAs (miRs) expression in stage I-IIIA lung adenocarcinoma (AC).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.11069 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 11069-11069

Author(s):

Marcin Tomasz Skrzypski ◽

Krzysztof Goryca ◽

Piotr Czapiewski ◽

Ewa Jassem ◽

Wojciech Biernat ◽

...

Keyword(s):

Prognostic Value ◽

Pulmonary Resection ◽

Cox Regression ◽

Geometric Mean ◽

Clinical Stage ◽

Distant Metastases ◽

Disease Recurrence ◽

Stage I ◽

Cell Lung Carcinoma ◽

Cox Regression Analysis

11069 Background: About 50% of NSCLC patients (pts) will develop distant metastases following pulmonary resection. Currently, apart from clinical stage at diagnosis, there are no reliable factors to select high-risk pts for adjuvant chemotherapy. We previously demonstrated prognostic value of 22 miRs in frozen samples of early squamous cell lung carcinoma, and the feasibility of their assessment in formalin fixed paraffin embedded (FFPE) samples (Skrzypski et. al. J Clin Oncol 2010;28;15s). In this study, we investigated the expression of 350 microRNAs in operable AC pts. Methods: FFPE tumor samples were obtained from 80 stage I-IIIA pts who underwent curative pulmonary resection, 48% of whom subsequently developed distant metastases. Median follow-up of pts who were disease recurrence-free was 5.8 years (range, 4.0-9.1 years). RNA was isolated from tumor tissue with RecoverAll kit (Ambion). Expression of 350 miRs was analyzed by qRT-PCR (Appliedbiosystems). Raw data were normalized vs. the geometric mean of U6, RNU48 and RNU44 expression. Relative miRs expression was correlated with distant metastases-free survival (MFS) and the mean expression was compared between the groups with and without relapse. Results: Expression of 41 miRs correlated with MFS in Cox regression analysis and 21 of these showed different level in pts with and without relapse in the t-Student test (both at p<0.05 level). The top prognostic miRs included miR-99a* (p=0.006), miR-1255B (p=0.005), miR-1233 (p=0.013) and miR-1303 (p=0.03); all previosly shown to be prognostic in AC or NSCLC. We also found 14 new microRNAs (patent pending) potentially prognostic for relapse in AC. Conclusions: Expression of selected miRs may aid in prediction of distant relapse in AC pts undergoing pulmonary resection.

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