scholarly journals Expression and Prognostic Characteristics of m6A RNA Methylation Regulators in Colon Cancer

2021 ◽  
Vol 22 (4) ◽  
pp. 2134
Author(s):  
Liting Huang ◽  
Jie Zhu ◽  
Weikaixin Kong ◽  
Peifeng Li ◽  
Sujie Zhu
Keyword(s):  
Colon Cancer ◽  
Clinical Information ◽  
The Cancer Genome Atlas ◽  
Cancer Cell Proliferation ◽  
Genetic Changes ◽  
Prognosis Model ◽  
Cancer Genome Atlas ◽  
M6a Rna Methylation ◽  
The Relationship

Colon cancer is a common and leading cause of death and malignancy worldwide. N6-methylation of adenosine (m6A) is the most common reversible mRNA modification in eukaryotes, and it plays a crucial role in various biological functions in vivo. Dysregulated expression and genetic changes of m6A regulators have been correlated with tumorigenesis, cancer cell proliferation, tumor microenvironment, and prognosis in cancers. This study used RNA-seq and colon cancer clinical data to explore the relationship between N6-methylation and colon cancer. Based on the seven m6A regulators related to prognosis, three molecular subgroups of colon cancer were identified. Surprisingly, we found that each subgroup had unique survival characteristics. We then identified three subtypes of tumors based on 299 m6A phenotype-related genes, and one subtype was characterized as an immunosuppressive tumor and patients in this subtype may be more suitable for immunotherapy than other subtypes. Finally, using m6A-related genes and clinical information from The Cancer Genome Atlas cohort, we constructed a prognosis model, and this model could be used to predict the prognosis of patients in clinics.

scholarly journals Involvement of Differentially Expressed microRNAs in the PEGylated Liposome Encapsulated 188Rhenium-Mediated Suppression of Orthotopic Hypopharyngeal Tumor

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3609
Author(s):  
Bing-Ze Lin ◽  
Shen-Ying Wan ◽  
Min-Ying Lin ◽  
Chih-Hsien Chang ◽  
Ting-Wen Chen ◽  
...  
Keyword(s):  
Therapeutic Efficacy ◽  
Survival Rates ◽  
Clinical Information ◽  
Hypopharyngeal Cancer ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas ◽  
Cancer Genome Atlas ◽  
Next Generation Sequencing Ngs

Hypopharyngeal cancer (HPC) accounts for the lowest survival rate among all types of head and neck cancers (HNSCC). However, the therapeutic approach for HPC still needs to be investigated. In this study, a theranostic 188Re-liposome was prepared to treat orthotopic HPC tumors and analyze the deregulated microRNA expressive profiles. The therapeutic efficacy of 188Re-liposome on HPC tumors was evaluated using bioluminescent imaging followed by next generation sequencing (NGS) analysis, in order to address the deregulated microRNAs and associated signaling pathways. The differentially expressed microRNAs were also confirmed using clinical HNSCC samples and clinical information from The Cancer Genome Atlas (TCGA) database. Repeated doses of 188Re-liposome were administrated to tumor-bearing mice, and the tumor growth was apparently suppressed after treatment. For NGS analysis, 13 and 9 microRNAs were respectively up-regulated and down-regulated when the cutoffs of fold change were set to 5. Additionally, miR-206-3p and miR-142-5p represented the highest fold of up-regulation and down-regulation by 188Re-liposome, respectively. According to Differentially Expressed MiRNAs in human Cancers (dbDEMC) analysis, most of 188Re-liposome up-regulated microRNAs were categorized as tumor suppressors, while down-regulated microRNAs were oncogenic. The KEGG pathway analysis showed that cancer-related pathways and olfactory and taste transduction accounted for the top pathways affected by 188Re-liposome. 188Re-liposome down-regulated microRNAs, including miR-143, miR-6723, miR-944, and miR-136 were associated with lower survival rates at a high expressive level. 188Re-liposome could suppress the HPC tumors in vivo, and the therapeutic efficacy was associated with the deregulation of microRNAs that could be considered as a prognostic factor.

scholarly journals Construction of a Risk Score Prognosis Model for Hepatocellular Carcinoma Based on Pyroptosis Related Genes

2021 ◽  
Author(s):  
Xin-yu Li ◽  
Li-xin Su ◽  
Ming-zhe Wen ◽  
Jian-xiong You ◽  
xi-tao Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Roc Curve ◽  
Prognostic Model ◽  
Operating Characteristic ◽  
Clinical Information ◽  
The Cancer Genome Atlas ◽  
Expression Data ◽  
Model Based ◽  
Prognosis Model ◽  
Cancer Genome Atlas

Abstract Background: In this study, a prognostic model based on pyroptosis-related genes was established to predict overall survival (OS) in patients with hepatocellular carcinoma(HCC).Methods: The gene expression data and clinical information of HCC patients were acquired from The Cancer Genome Atlas (TCGA). Using bioinformatics analysis, this predictive signature was constructed and validated. The performance of predictive signature was assessed by the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC). Results: A total of 3 pyroptosis-related genes (BAK1, GSDME, and NOD2) were used to construct a survival prognostic model, and experimental validation performed using an experimental cohort. The prognosis model exhibited good performance based on the AUC (AUC: 0.826 at 1 years, 0.796 at 3 years, 0.867 at 5 years). The calibration plots showed excellent calibration.Conclusion: In this study, a novel prognostic model based on three pyroptosis-related genes is constructed and used to predict the prognosis of HCC patients. The model can accurately and conveniently predict the 1- 3-and 5-year OS of HCC patients.

scholarly journals Expression and Prognostic Characteristics of Ferroptosis-Related Genes in Colon Cancer

2021 ◽  
Vol 22 (11) ◽  
pp. 5652
Author(s):  
Jie Zhu ◽  
Weikaixin Kong ◽  
Zhengwei Xie
Keyword(s):  
Colon Cancer ◽  
The Cancer Genome Atlas ◽  
Braf Mutations ◽  
Mutation Burden ◽  
The Status ◽  
Prognosis Model ◽  
Cancer Genome Atlas ◽  
Causes Of Mortality ◽  
New Type ◽  
Checkpoint Genes

Ferroptosis is a new type of programmed cell death, which occurs with iron dependence. Previous studies have showed that ferroptosis plays an important regulatory role in the occurrence and development of tumors. Colon cancer is one of the major morbidities and causes of mortality in the world. This study used RNA-seq and colon cancer clinical data to explore the relationship between ferroptosis-related genes and colon cancer. Based on the fifteen prognostic ferroptosis-related genes, two molecular subgroups of colon cancer were identified. Surprisingly, we also found cluster2 was characterized by lower mutation burden and expression of checkpoint genes, better survival, and higher expression of NOX1. Moreover, cluster2 has fewer BRAF mutations. We also found the expression of NOX1 is related to the status of BRAF. Finally, using 15 ferroptosis-related genes from The Cancer Genome Atlas cohort, we constructed a prognosis model, and this model may be used to predict the prognosis of patients in clinics.

scholarly journals TRIM27 interacts with Iκbα to promote the growth of human renal cancer cells through regulating the NF-κB pathway

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chengwu Xiao ◽  
Wei Zhang ◽  
Meimian Hua ◽  
Huan Chen ◽  
Bin Yang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Protein Levels ◽  
Kaplan Meier ◽  
Cancer Genome Atlas

Abstract Background The tripartite motif (TRIM) family proteins exhibit oncogenic roles in various cancers. The roles of TRIM27, a member of the TRIM super family, in renal cell carcinoma (RCC) remained unexplored. In the current study, we aimed to investigate the clinical impact and roles of TRIM27 in the development of RCC. Methods The mRNA levels of TRIM27 and Kaplan–Meier survival of RCC were analyzed from The Cancer Genome Atlas database. Real-time PCR and Western blotting were used to measure the mRNA and protein levels of TRIM27 both in vivo and in vitro. siRNA and TRIM27 were exogenously overexpressed in RCC cell lines to manipulate TRIM27 expression. Results We discovered that TRIM27 was elevated in RCC patients, and the expression of TRIM27 was closely correlated with poor prognosis. The loss of function and gain of function results illustrated that TRIM27 promotes cell proliferation and inhibits apoptosis in RCC cell lines. Furthermore, TRIM27 expression was positively associated with NF-κB expression in patients with RCC. Blocking the activity of NF-κB attenuated the TRIM27-mediated enhancement of proliferation and inhibition of apoptosis. TRIM27 directly interacted with Iκbα, an inhibitor of NF-κB, to promote its ubiquitination, and the inhibitory effects of TRIM27 on Iκbα led to NF-κB activation. Conclusions Our results suggest that TRIM27 exhibits an oncogenic role in RCC by regulating NF-κB signaling. TRIM27 serves as a specific prognostic indicator for RCC, and strategies targeting the suppression of TRIM27 function may shed light on future therapeutic approaches.

scholarly journals HNRNPH1-stabilized LINC00662 promotes ovarian cancer progression by activating the GRP78/p38 pathway

Oncogene ◽  
2021 ◽  
Author(s):  
Yong Wu ◽  
Qinhao Guo ◽  
Xingzhu Ju ◽  
Zhixiang Hu ◽  
Lingfang Xia ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Prognostic Indicator ◽  
Mapk Signaling ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Proliferation And Metastasis ◽  
Nuclear Ribonucleoprotein

AbstractNumerous studies suggest an important role for copy number alterations (CNAs) in cancer progression. However, CNAs of long intergenic noncoding RNAs (lincRNAs) in ovarian cancer (OC) and their potential functions have not been fully investigated. Here, based on analysis of The Cancer Genome Atlas (TCGA) database, we identified in this study an oncogenic lincRNA termed LINC00662 that exhibited a significant correlation between its CNA and its increased expression. LINC00662 overexpression is highly associated with malignant features in OC patients and is a prognostic indicator. LINC00662 significantly promotes OC cell proliferation and metastasis in vitro and in vivo. Mechanistically, LINC00662 is stabilized by heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1). Moreover, LINC00662 exerts oncogenic effects by interacting with glucose-regulated protein 78 (GRP78) and preventing its ubiquitination in OC cells, leading to activation of the oncogenic p38 MAPK signaling pathway. Taken together, our results define an oncogenic role for LINC00662 in OC progression mediated via GRP78/p38 signaling, with potential implications regarding therapeutic targets for OC.

scholarly journals Exceptional Chemotherapy Response in Metastatic Colorectal Cancer Associated With Hyper-Indel–Hypermutated Cancer Genome and Comutation of POLD1 and MLH1

2017 ◽  
pp. 1-12
Author(s):  
Manish R. Sharma ◽  
James T. Auman ◽  
Nirali M. Patel ◽  
Juneko E. Grilley-Olson ◽  
Xiaobei Zhao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Somatic Mutation ◽  
Mutation Rate ◽  
Germ Line ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Response To Chemotherapy ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Purpose A 73-year-old woman with metastatic colon cancer experienced a complete response to chemotherapy with dose-intensified irinotecan that has been durable for 5 years. We sequenced her tumor and germ line DNA and looked for similar patterns in publicly available genomic data from patients with colorectal cancer. Patients and Methods Tumor DNA was obtained from a biopsy before therapy, and germ line DNA was obtained from blood. Tumor and germline DNA were sequenced using a commercial panel with approximately 250 genes. Whole-genome amplification and exome sequencing were performed for POLE and POLD1. A POLD1 mutation was confirmed by Sanger sequencing. The somatic mutation and clinical annotation data files from the colon (n = 461) and rectal (n = 171) adenocarcinoma data sets were downloaded from The Cancer Genome Atlas data portal and analyzed for patterns of mutations and clinical outcomes in patients with POLE- and/or POLD1-mutated tumors. Results The pattern of alterations included APC biallelic inactivation and microsatellite instability high (MSI-H) phenotype, with somatic inactivation of MLH1 and hypermutation (estimated mutation rate > 200 per megabase). The extremely high mutation rate led us to investigate additional mechanisms for hypermutation, including loss of function of POLE. POLE was unaltered, but a related gene not typically associated with somatic mutation in colon cancer, POLD1, had a somatic mutation c.2171G>A [p.Gly724Glu]. Additionally, we noted that the high mutation rate was largely composed of dinucleotide deletions. A similar pattern of hypermutation (dinucleotide deletions, POLD1 mutations, MSI-H) was found in tumors from The Cancer Genome Atlas. Conclusion POLD1 mutation with associated MSI-H and hyper-indel–hypermutated cancer genome characterizes a previously unrecognized variant of colon cancer that was found in this patient with an exceptional response to chemotherapy.

Identification of a lncRNA prognostic signature-related to stem cell index and its significance in colorectal cancer

2021 ◽  
Author(s):  
Xiao-Cheng Wang ◽  
Ya Liu ◽  
Fei-Wu Long ◽  
Liang-Ren Liu ◽  
Chuan-Wen Fan
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prognostic Markers ◽  
The Cancer Genome Atlas ◽  
Prognostic Signature ◽  
Free Survival ◽  
Cancer Genome Atlas ◽  
Bioinformatic Approaches ◽  
Cell Phenotypes ◽  
The Relationship

Background: The relationship between long noncoding RNAs (lncRNAs) and the mRNA stemness index (mRNAsi) in colorectal cancer (CRC) is still unclear. Materials & methods: The mRNAsi, mRNAsi-related lncRNAs and their clinical significance were analyzed by bioinformatic approaches in The Cancer Genome Atlas (TCGA)-COREAD dataset. Results: mRNAsi was negatively related to pathological features but positively related to overall survival and recurrence-free survival in CRC. A five mRNAsi-related lncRNAs prognostic signature was further developed and showed independent prognostic factors related to overall survival in CRC patients, due to the five mRNAsi-related lncRNAs involved in several pathways of the cancer stem cells and malignant cancer cell phenotypes. Conclusion: The present study highlights the potential roles of mRNAsi-related lncRNAs as alternative prognostic markers.

scholarly journals Prognostic Value of A Risk Score Model Constructed By m6A Methylation Regulators In Breast Cancer

2021 ◽  
Author(s):  
Xiaowei Qiu ◽  
Qiaoli Zhang ◽  
Jingnan Xu ◽  
Xin Jiang ◽  
Xuewei Qi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Score ◽  
Prognostic Value ◽  
Validation Cohort ◽  
Risk Group ◽  
The Cancer Genome Atlas ◽  
Rna Methylation ◽  
Model Based ◽  
Prognosis Model ◽  
M6a Rna Methylation

Abstract Background: N6-methyladenosine (m6A) methylation modification can affect the tumorigenesis, progression, and metastasis of breast cancer (BC). Up to now, a prognostic model based on m6A methylation regulators for BC is still lacking. This study aimed to construct an accurate prediction prognosis model by m6A methylation regulators for BC patients.Methods: After processing of The Cancer Genome Atlas (TCGA) datasets, the differential expression and correlation analysis of m6A RNA methylation regulators were applied. Next, tumor samples were clustered into different groups and clinicopathologic features in different clusters were explored. By univariate Cox and Least Absolute Shrinkage and Selection Operator (LASSO) analysis, m6A regulators with prognostic value were identified to develop a prediction model. Furthermore, we constructed and validated a predictive nomogram to predict the prognosis of BC patients.Results: 19 m6A related genes were extracted and 908 BC patients enrolled from TCGA dataset. After univariate Cox and LASSO analysis, 3 m6A RNA methylation regulators (YTHDF3, ZC3H13 and HNRNPC) were selected to establish the prognosis model based on median risk score (RS) in training and validation cohort. With the increasing of RS, the expression levels of YTHDF3 and ZC3H13 were individually elevated, while the HNRNPC expressed decreasingly. By survival analysis and Receiver Operating Characteristic (ROC) curve, we found that the overall survival (OS) of high-risk group was significantly shorter than that of the low-risk group based on Kaplan-Meier (KM) analysis in each cohort. Univariate and multivariate analysis identified the RS, age, and pathological stage are independent prognostic factors. A nomogram was constructed to predict 1- and 3-year OS and the calibration plots validate the performance. The C-index of nomogram reached 0.757 (95% CI:0.7-0.814) in training cohort and 0.749 (95% CI:0.648-0.85) in validation cohort, respectively.Conclusions: We successfully constructed a predictive prognosis model by m6A RNA methylation regulators. These results indicated that the m6A RNA methylation regulators are potential therapeutic targets of BC patients.

scholarly journals CYSTM1: A Novel Biomarker for Hepatocellular Carcinoma Prognosis

2021 ◽  
Author(s):  
Jun Du ◽  
Jinguo Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Early Stage ◽  
Human Tumor ◽  
The Cancer Genome Atlas ◽  
Data Set ◽  
Kaplan Meier ◽  
Cancer Genome Atlas ◽  
Cox Proportional Hazard Regression ◽  
The Relationship

Abstract Background: The expression and molecular mechanism of cysteine rich transmembrane module containing 1 (CYSTM1) in human tumor cells remains unclear. The aim of this study was to determine whether CYSTM1 could be used as a potential prognostic biomarker for hepatocellular carcinoma (HCC).Methods: We first demonstrated the relationship between CYSTM1 expression and HCC in various public databases. Secondly, Kaplan–Meier analysis and Cox proportional hazard regression model were performed to evaluate the relationship between the expression of CYSTM1 and the survival of HCC patients which data was downloaded in the cancer genome atlas (TCGA) database. Finally, we used the expression data of CYSTM1 in TCGA database to predict CYSTM1-related signaling pathways through bioinformatics analysis.Results: The expression level of CYSTM1 in HCC tissues was significantly correlated with T stage (p = 0.039). In addition, Kaplan–Meier analysis showed that the expression of CYSTM1 was significantly associated with poor prognosis in patients with early-stage HCC (p = 0.003). Multivariate analysis indicated that CYSTM1 is a potential predictor of poor prognosis in HCC patients (p = 0.036). The results of biosynthesis analysis demonstrated that the data set of CYSTM1 high expression was mainly enriched in neurodegeneration and oxidative phosphorylation pathways.Conclusion: CYSTM1 is an effective biomarker for the prognosis of patients with early-stage HCC and may play a key role in the occurrence and progression of HCC.

scholarly journals Identification and Validation of a Glycolysis Related Metabolic Reprogramming Gene Signature for Predicting Survival in Colon Cancer Patients

2021 ◽  
Author(s):  
Gang Liu ◽  
Xiaowang WU ◽  
Jian Chen
Keyword(s):  
Colon Cancer ◽  
Prediction Model ◽  
Cox Regression ◽  
Malignant Tumors ◽  
Gene Signature ◽  
Metabolic Reprogramming ◽  
Risk Scores ◽  
Cox Regression Analysis ◽  
Prognosis Model ◽  
The Relationship

Abstract Background Colon cancer (CC) is one of the most common gastrointestinal malignant tumors with high mortality rate. Because of malignancy and easily metastasis feather, and limited treatments, the prognosis of CC remains poor. Glycolysis is a metabolic process of glucose in anoxic environments which is an important way to provide energy for tumor. The role of glycolysis in CC largely remains unknown and is necessary to be explored. Method In our study, we analyzed glycolysis related genes expression in CC, patients gene expression and corresponding clinical data were downloaded from GEO dataset, glycolysis related genes sets were collected from Msigdb. Through COX regression analysis, prognosis model based on glycolysis-related genes was established. The efficacy of gene model was tested by Survival analysis, ROC analysis and PCA analysis. Furthermore, the relationship between risk scores and clinical characteristic was researched. Results Our findings identified 13 glycolysis related genes (NUP107, SEC13, ALDH7A1, ALG1, CHPF, FAM162A, FBP2, GALK1, IDH1, TGFA, VLDLR, XYLT2 and OGDHL) consisted prognostic prediction model with relative high accuracy. The relationship between prediction model and clinical feathers were specifically studied, results showed age > 65years, TNM III-IV, T3-4, N1-3, M1 and high-risk score were independent prognostic risk factors with poorer prognosis. Finally, model genes were significantly expressed and EMT were activated in CC patients. Conclusion This study provided a new aspect to advance our understanding in the potential mechanism of glycolysis in CC.

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