scholarly journals Molecular subtyping and prognostic assessment of prostate cancer based on consensus genes

2021 ◽  
Author(s):  
Jialin Meng ◽  
Yu Guan ◽  
Bijun Wang ◽  
Lei Chen ◽  
Junyi Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cox Regression ◽  
Expression Profiles ◽  
Staging System ◽  
Migration And Invasion ◽  
Molecular Subtyping ◽  
Cox Regression Analysis ◽  
Prognostic Assessment ◽  
Selection Operator

Abstract Prostate cancer (PCa) is one of the most common malignancies in men all over the world. We performed molecular subtyping and prognostic assessment based on consensus genes in patients with PCa. Five cohorts containing 1,046 PCa patients with RNA expression profiles and recorded clinical follow-up information were included. Univariate, multivariate Cox regression analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression was used to select prognostic genes and establish the signature. Immunohistochemistry staining, cell proliferation, migration and invasion assay were used to assess the biological function of key genes. 39 intersecting consensus prognostic genes from five independent cohorts were identified (P < 0.05). Subsequently, an eleven-consensus-gene-based classifier was established. Besides, multivariate Cox regression analyses proved that the classifier served as an independent indicator of recurrence-free survival in three of five cohorts. Combined receiver operating character (ROC) achieved synthesized effects by combining the classifier with clinicopathological features in four of five cohorts. SRD5A2 inhibits the cell proliferation, while ITGA11 promote cell migration and invasion, of which might through PI3K/AKT signaling pathway. To conclude, we establish and validate an eleven-consensus-gene-based classifier, which adds prognostic value to the currently available staging system.

scholarly journals MicroRNA-99b predicts clinical outcome of osteosarcoma and suppresses tumor cell proliferation, migration and invasion

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Xin Shi ◽  
Xingfa Guan
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Prognostic Value ◽  
Cox Regression ◽  
Expression Profiles ◽  
Migration And Invasion ◽  
Aberrant Expression ◽  
Cox Regression Analysis ◽  
Normal Tissues

Abstract Background Osteosarcoma (OS) is a malignancy predominantly occurred in children and adolescents. Numerous microRNAs are involved in the pathogenesis of various cancers. This study aimed to investigate the expression profiles of miR-99b and its prognostic value in OS patients, and further analyze the biological function of miR-99b in the tumor progression by using OS cells. Methods Expression of miR-99b was measured using quantitative real-time PCR. Kaplan-Meier survival curves and Cox regression analysis were performed to evaluate the prognostic value of miR-99b. OS cell lines were used to investigate the effects of miR-99b on cell proliferation, migration and invasion. Results A significant decreased expression of miR-99b was observed in the OS tissues and cell lines respectively compared with the normal tissues and cells. Aberrant expression of miR-99b was associated with the patients’ metastasis and TNM stage, and could be used to predict the prognosis of OS. The expression of miR-99b was regulated in vitro by cell transfection, and we found that the overexpression of miR-99b led to suppressed cell proliferation, migration and invasion, whereas the knockdown of miR-99b resulted in the opposite results. Conclusions In one word, the aberrantly expressed miR-99b serves a prognostic biomarker for OS patients. OS cell proliferation, migration and invasion can be inhibited by the overexpression of miR-99b, suggesting that the methods to increase miR-99b expression may be novel therapeutic strategies in OS.

scholarly journals Up-Regulation of Long Noncoding RNA CCAL Predicts Poor Patient Prognosis and Promotes Tumor Metastasis in Osteosarcoma

2017 ◽  
Vol 32 (1) ◽  
pp. 108-112 ◽  
Author(s):  
Da-Kai Zhou ◽  
Xi-Wang Yang ◽  
Huining Li ◽  
Yongbo Yang ◽  
Zhen-Jun Zhu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Noncoding Rna ◽  
Tumor Metastasis ◽  
Cox Regression ◽  
Migration And Invasion ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Patient Prognosis ◽  
Invasion Assays

Background Long noncoding RNAs (IncRNAs) play essential roles in tumor progression. Aberrant colorectal cancer-associated IncRNA (CCAL) has been found in colorectal cancer. However, the function of IncRNA CCAL in osteosarcoma (OS) remains unclear. Methods Quantitative real-time PCR (qRT-PCR) was performed to measure CCAL expression in OS tissues and adjacent nontumor tissues. The correlation betweent CCAL expression and clinicopathological features and prognosis was also analyzed. In addition, the function of CCAL was further evaluated by cell proliferation, migration and invasion assays. Results We showed that CCAL was significantly up-regulated in OS tissues compared with adjacent nontumor tissues. Increased expression of CCAL was correlated with advanced TNM stage and metastasis. Kaplan-Meier analysis demonstrated that patients with high CCAL expression had lower overall survival than those with low CCAL expression. Multivariate Cox regression analysis indicated that CCAL expression might be an independent prognostic factor for OS patients. In addition, functional assays showed that decreased CCAL expression could inhibit OS cell proliferation, migration and invasion ability. Conclusions Our findings suggested that CCAL plays critical roles in OS progression and could act as a therapeutic target in the treatment of OS.

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 Enhanced expression of miR-889 forecasts an unfavorable prognosis and facilitates cell progression in hepatocellular carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
He Wang ◽  
Huiwen Wang ◽  
Wenyu Cui ◽  
Qiao Zhang ◽  
Jing Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cox Regression ◽  
Malignant Tumors ◽  
Prognostic Significance ◽  
High Expression ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Cox Regression Analysis

Abstract Background As a new type of molecular marker, microRNAs (miRNAs) can be used for early diagnosis and prognosis prediction of malignant tumors, and has broad clinical application prospects. This paper mainly studies the important role of miR-889 in the occurrence and development of hepatocellular carcinoma and the prognostic significance of miR-889 in hepatocellular carcinoma. Methods Quantitative real-time PCR analysis detected the expression levels of miR-889 in hepatocellular carcinoma tissues and cell lines. Kaplan-Meier curve and Cox regression analysis were used to explore the prognostic significance of miR-889 in hepatocellular carcinoma. The CCK-8 and Transwell assays assay were used to assess cell proliferation, migration, and invasion abilities ability. Results The expression of miR-889 in hepatocellular carcinoma tissues was significantly higher than that in adjacent tissues. Overexpression of miR-889 was significantly associated with TNM stage, hepatitis B virus infection, and cirrhosis. Patients with high miR-889 expression had shorter overall survival than those with low miR-889 expression. And functional studies in two hepatocellular carcinoma cell lines have shown that overexpression of miR-889 significantly promoted cell proliferation, migration, and invasion in vitro. Conclusions Overall, miR-889 was upregulated in hepatocellular carcinoma tissues and cell lines, and overexpression of miR-889 promoted cell proliferation, migration, and invasion in hepatocellular carcinoma cells. Based on our findings, high expression of miR-889 may promote the progression of hepatocellular carcinoma, and high expression of miR-889 is also forecasted for an unfavorable prognosis in hepatocellular carcinoma.

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 MiR-455-3p downregulation facilitates cell proliferation and invasion and predicts poor prognosis of osteosarcoma

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Xijun Yi ◽  
Yafei Wang ◽  
Shijie Xu
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Cox Regression ◽  
Clinical Stage ◽  
Prognostic Indicator ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Cox Regression Analysis ◽  
Cox Analysis

Abstract Background Osteosarcoma (OS) is one of the most primary malignant bone tumors, mainly attracting children and young adults. The microRNAs are mentioned to play vital roles in many cancers, including OS. The purpose of this study was to explore the expression and function of miR-455-3p in OS and predict the potential effects in clinical diagnosis and prognosis. Method We conducted quantitative real-time PCR to assess the expression of miR-455-3p in OS tissues and cell lines. The Cell Counting Kit-8 assay, Transwell assay, and flow cytometry were performed to assess the ability of miR-455-3p on cell proliferation, migration, invasion, and apoptosis. Kaplan–Meier curve and Cox regression analysis were used to demonstrate the survival outcome. Results This study revealed that the expression of miR-455-3p was decreased in OS tissues and cell lines. The dysregulation of miR-455-3p was in association with tumor size, distant metastasis, and clinical stage. Patients with high miR-455-3p expression had a satisfying survival rate. Multivariate Cox analysis indicated that miR-455-3p was a promising prognostic indicator. Expression of miR-455-3p could inhibit the proliferation, migration, and invasion, and facilitate apoptosis of OS cells in vitro. Conclusion These results indicated the miR-455-3p was a potential clinical therapeutic target and prognostic biomarker by suppressing the proliferation, migration, and invasion, as well as enhancing cell apoptosis.

Overexpression of miR-127 Predicts Poor Prognosis and Contributes to the Progression of Papillary Thyroid Cancer by Targeting REPIN1

2020 ◽  
Author(s):  
Yinghe Sun ◽  
Wenhai Sun ◽  
Hui Hua ◽  
Jianhua Zhang ◽  
Qianqian Yu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Tnm Stage ◽  
Prognostic Indicators ◽  
Migration And Invasion ◽  
Papillary Thyroid ◽  
Cox Regression Analysis

AbstractPapillary thyroid cancer (PTC) is a major kind of thyroid cancer with increasing recurrence and metastasis. MiR-127 has been demonstrated to play roles in many cancers with dysregulation. However, the function of miR-127 is still unknown. This study aimed to explore a novel biomarker for the progression and prognosis of PTC. A set of 118 patients with PTC were collected from the Affiliated Hospital of Qingdao University. qRT-PCR was used to detect the expression of miR-127 in PTC tissues and cells. The association between miR-127 expression and the clinicopathological features of patients were evaluated by the χ2 test, and the prognostic value of miR-127 was evaluated by Kaplan–Meier analysis and Cox regression analysis. The effect of miR-127 on cell proliferation, migration, and invasion of PTC was analyzed by CCK-8 and transwell assay. miR-127 was found to be upregulated in PTC tissues and cells correlated with the TNM stage and poor prognosis of PTC patients. MiR-127 and the TNM stage were considered as two independent prognostic indicators for PTC. Moreover, overexpression of miR-127 significantly enhanced cell proliferation, migration, and invasion of PTC by targeting REPIN1. miR-127 may be involved in the progression of PTC, which provides a new therapeutic strategy for PTC.

scholarly journals Identification of a Costimulatory Molecule-Related Signature for Predicting Prognostic Risk in Prostate Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Shengdong Ge ◽  
Xiaoliang Hua ◽  
Juan Chen ◽  
Haibing Xiao ◽  
Li Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immune Cell ◽  
Cox Regression ◽  
Expression Profiles ◽  
Costimulatory Molecule ◽  
Prognostic Significance ◽  
Gene Expression Profiles ◽  
Treatment Decision ◽  
Prognostic Signature ◽  
Cox Regression Analysis

Costimulatory molecules have been proven to enhance antitumor immune responses, but their roles in prostate cancer (PCa) remain unexplored. In this study, we aimed to explore the gene expression profiles of costimulatory molecule genes in PCa and construct a prognostic signature to improve treatment decision making and clinical outcomes. Five prognosis-related costimulatory molecule genes (RELT, TNFRSF25, EDA2R, TNFSF18, and TNFSF10) were identified, and a prognostic signature was constructed based on these five genes. This signature was an independent prognostic factor according to multivariate Cox regression analysis; it could stratify PCa patients into two subgroups with different prognoses and was highly associated with clinical features. The prognostic significance of the signature was well validated in four different independent external datasets. Moreover, patients identified as high risk based on our prognostic signature exhibited a high mutation frequency, a high level of immune cell infiltration and an immunosuppressive microenvironment. Therefore, our signature could provide clinicians with prognosis predictions and help guide treatment for PCa patients.

scholarly journals PCAT1 is a poor prognostic factor in endometrial carcinoma and associated with cancer cell proliferation, migration and invasion

2019 ◽  
Author(s):  
Xiaohuan Zhao ◽  
Yali Fan ◽  
Changqiong Lu ◽  
Hongfang Li ◽  
Ning Zhou ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endometrial Carcinoma ◽  
Cell Lines ◽  
Cancer Progression ◽  
Cox Regression ◽  
Myometrial Invasion ◽  
B Cell Lymphoma ◽  
Migration And Invasion ◽  
Poor Prognostic Factor ◽  
Cox Regression Analysis

Long non-coding RNAs (lncRNAs) are emerging as important modulators of cancer progression, among which prostate cancer-associated transcript 1 (PCAT1) has been shown to be an oncogene in several tumors. However, the clinical significance and biological function of PCAT1 in endometrial carcinoma (EC) remain unclear. In this study, we used 89 EC tissues and HEC-1B, Ishikawa, RL95-2 and AN3CA EC cell lines. We found elevated expression levels of PCAT1 in EC tissues and cell lines using reverse transcription qPCR (RT-qPCR). The prognostic value of PCAT1 was determined using Kaplan–Meier survival and Cox regression analysis. The results showed that higher PCAT1 expression was positively correlated with FIGO stage, myometrial invasion, lymph node metastasis, and a shorter overall survival. A series of functional assays showed that the knockdown of PCAT1 by small interfering RNA (siRNA) targeting PCAT1 (siPCAT1) suppressed cell proliferation, migration and invasion, but promoted apoptosis. Western blot analysis further showed that B-cell lymphoma 2 (Bcl-2), vimentin and N-cadherin were downregulated, but E-cadherin and Bcl-2-associated death promoter (Bad) were upregulated in PCAT1-silenced EC cells. Taken together, our results underscore the oncogenic role of PCAT1 in EC and show that PCAT1 may be a potential therapeutic target in EC treatment.

scholarly journals Identification and Validation of a PPP1R12A-Related Five-Gene Signature Associated With Metabolism to Predict the Prognosis of Patients With Prostate Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhihao Zou ◽  
Ren Liu ◽  
Yingke Liang ◽  
Rui Zhou ◽  
Qishan Dai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cox Regression ◽  
Expression Profiles ◽  
Affinity Purification ◽  
Disease Free Survival ◽  
Gene Signature ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Free Survival ◽  
Cox Regression Analysis

BackgroundProstate cancer (PCa) is the most common malignant male neoplasm in the American male population. Our prior studies have demonstrated that protein phosphatase 1 regulatory subunit 12A (PPP1R12A) could be an efficient prognostic factor in patients with PCa, promoting further investigation. The present study attempted to construct a gene signature based on PPP1R12A and metabolism-related genes to predict the prognosis of PCa patients.MethodsThe mRNA expression profiles of 499 tumor and 52 normal tissues were extracted from The Cancer Genome Atlas (TCGA) database. We selected differentially expressed PPP1R12A-related genes among these mRNAs. Tandem affinity purification-mass spectrometry was used to identify the proteins that directly interact with PPP1R12A. Gene set enrichment analysis (GSEA) was used to extract metabolism-related genes. Univariate Cox regression analysis and a random survival forest algorithm were used to confirm optimal genes to build a prognostic risk model.ResultsWe identified a five-gene signature (PPP1R12A, PTGS2, GGCT, AOX1, and NT5E) that was associated with PPP1R12A and metabolism in PCa, which effectively predicted disease-free survival (DFS) and biochemical relapse-free survival (BRFS). Moreover, the signature was validated by two internal datasets from TCGA and one external dataset from the Gene Expression Omnibus (GEO).ConclusionThe five-gene signature is an effective potential factor to predict the prognosis of PCa, classifying PCa patients into high- and low-risk groups, which might provide potential novel treatment strategies for these patients.

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