scholarly journals Basic Pan-Cancer Analysis of the Carcinogenic Effects of Cyclin-Dependent Kinase 4 (CDK4) in Human Surface Tumors

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Jingping Wu ◽  
Tinghan Deng ◽  
Yuanen Huang ◽  
Hongbin Cheng

Although the evidence based on current human, animal, or molecular biology can explain some of the relationships between CDK4 and cancer, there is no pan-cancer analysis of the gene CDK4 in human skin tumors. Therefore, the potential carcinogenic effects of CDK4 in 33 tumors were initially explored in the datasets of the GEO (Gene Expression Omnibus) and the CGA (Cancer Genome Atlas). We found that CDK4 was highly expressed in most cancers and that CDK4 performance levels significantly correlated with the prognosis of cancer patients. These were found in our preliminary exploration. In addition, we used the dataset in tumors such as cutaneous melanoma or lung adenocarcinoma and found increased levels of phosphorylation of r24 l/C/h/s. In addition, fibroblast infiltration associated with CDK4 cancer was observed in head and neck, sarcoma, and melanoma skin. Using this pan-cancer study, our group has provided a comprehensive preliminary demonstration of the oncogenic effects of the CDK4 gene on different human skin tumors.

2020 ◽  
Vol 13 (2) ◽  
pp. 26
Author(s):  
George S. Scaria ◽  
Betsy T. Kren ◽  
Mark A. Klein

Pancreatic cancer, hepatocellular carcinoma (HCC), and mesothelioma are treatment-refractory cancers, and patients afflicted with these cancers generally have a very poor prognosis. The genomics of these tumors were analyzed as part of The Cancer Genome Atlas (TCGA) project. However, these analyses are an overview and may miss pathway interactions that could be exploited for therapeutic targeting. In this study, the TCGA Pan-Cancer datasets were queried via cBioPortal for correlations among mRNA expression of key genes in the cell cycle and mitochondrial (mt) antioxidant defense pathways. Here we describe these correlations. The results support further evaluation to develop combination treatment strategies that target these two critical pathways in pancreatic cancer, hepatocellular carcinoma, and mesothelioma.


2021 ◽  
Author(s):  
Lihong Huang ◽  
ruoling zheng ◽  
Huasong Gong ◽  
Yongchao Qiao

Abstract Although emerging cells or animals based evidence supports an association between nuclear factor kappa-B1 (NF-κB1) cells and cancers, there has no pan-cancer analysis. Therefore, based on TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) data sets, we first studied the potential carcinogenic effect of NF-κB1 in 33 tumors. As we not only found high expression of NF-κB1 in most tumors, but also found that NF-κB1 expression is closely related to the prognosis of tumor patients. Enhanced phosphorylation of S893 was observed in several tumors, such as breast cancer, uterine corpus endometrial carcinoma or lung adenocarcinoma. In thymoma, NF-κB1 expression was relevant to CD8+ T-cell infiltration levels, and tumor-associated fibroblast infiltration has also seen in other tumors, such as uterine corpus endometrial carcinoma or glioblastoma multiforme. In addition, the functional mechanism of NF-κB1 also involves the related functions of protein processing and RNA metabolism. In this study, NF-κB1 was pan-cancer study in order to have a systematic and comprehensive understanding of the carcinogenic effect of NF-κB1 in different tumors.


2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Jie Li ◽  
Ye Tong ◽  
Zhi Wang ◽  
Yi Liu ◽  
Xiaobo Dai ◽  
...  

Recently, it was reported that ubiquilin 4 (UBQLN4) alteration was associated with genomic instability in some cancers. However, whether UBQLN4 is a valuable biomarker for the prognosis of immunotherapy in pan-cancer was not identified. We evaluated the biologic and oncologic significance of UBQLN4 in pan-cancer at multiomics level, such as expression, mutation, copy number variation (CNV), methylation, and N6-methyladenosine (m6A) methylation. These omics data were obtained from several public databases, including Oncomine, The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), the Genotype-Tissue Expression (GTEx), the Human Protein Atlas (HPA), Gene Set Cancer Analysis (GSCA), m6A-Atlas, CancerSEA, and RNAactDrug. We found that UBQLN4 mRNA and protein were overexpressed in most cancer types, and the expression, mutation, CNV, and methylation of UBQLN4 were associated with the prognosis of some cancers. Mechanistically, UBQLN4 was involved in angiogenesis, DNA damage, apoptosis, and the pathway of PI3K/AKT and TSC/mTOR. Moreover, UBQLN4 mRNA was significantly correlated with immune checkpoints, tumor mutational burden (TMB), microsatellite instability (MSI), and mismatch repair (MMR). And, the correlation among UBQLN4 mRNA, CNV, and methylation and immune microenvironment was also identified. Furthermore, UBQLN4 was associated with the sensitivity of chemotherapy and targeted drugs at multiomics level. In conclusion, UBQLN4 was a promising prognostic biomarker of immune-related therapy in pan-cancer.


2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Biao Wu ◽  
Yumeng Wu ◽  
Xianlin Guo ◽  
Yanping Yue ◽  
Yuanyuan Li ◽  
...  

Several studies have suggested that coatomer protein complex subunit beta 2 (COPB2) may act as an oncogene in various cancer types. However, no systematic pan-cancer analysis has been performed to date. Therefore, the present study analyzed the potential oncogenic role of COPB2 using TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) datasets. The majority of the cancer types overexpressed the COPB2 protein, and its expression significantly correlated with tumor prognosis. In certain tumors, such as those found in breast and ovarian tissues, phosphorylated S859 exhibited high expression. It was found that mutations of the COPB2 protein in kidney and endometrial cancers exhibited a significant impact on patient prognosis. It is interesting to note that COPB2 expression correlated with the number of cancer-associated fibroblasts in certain tumors, such as cervical and endocervical cancers and colon adenocarcinomas. In addition, COPB2 was involved in the transport of substances and correlated with chemotherapy sensitivity. This is considered the first pan-tumor study, which provided a relatively comprehensive understanding of the mechanism by which COPB2 promotes cancer growth.


2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Shujie Ruan ◽  
Jingping Shi ◽  
Ming Wang ◽  
Zhechen Zhu

Plakophilins (PKPs) act as a key regulator of different signaling programs and control a variety of cellular processes ranging from transcription, protein synthesis, growth, proliferation, and tumor development. The function and possible mechanism of PKP3 in ovarian cancer (OC) remain unknown. It is extremely important to investigate the expression and prognostic values of PKP3, as well as their possible mechanisms, and immune infiltration in OC. Therefore, in this paper we explored the potential oncogenic role of PKP3 in 33 tumors based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. The result outcomes showed that PKP3 is highly expressed in most cancers, and the expression level and prognosis of PKP3 showed little significance in cancer patients. Moreover, oncologists have found that members of the plakophilin family have different degrees of abnormality in ovarian cancer. PKP3 played a key part in carcinogenesis and aggressiveness of OC as well as malignant biological activity and can be used as a biomarker for early diagnosis and prognosis evaluation in OC.


2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Nathan D. Seligson ◽  
Richard D. Maradiaga ◽  
Colin M. Stets ◽  
Howard M. Katzenstein ◽  
Sherri Z. Millis ◽  
...  

AbstractSarcomas harboring EWSR1-NFATc2 fusions have historically been categorized and treated as Ewing sarcoma. Emerging evidence suggests unique molecular characteristics and chemotherapy sensitivities in EWSR1-NFATc2 fusion positive sarcomas. Comprehensive genomic profiles of 1024 EWSR1 fusion positive sarcomas, including 14 EWSR1-NFATc2 fusions, were identified in the FoundationCore® database. Additional data from the Gene Expression Omnibus, the Genomics of Drug Sensitivity in Cancer and The Cancer Genome Atlas datasets were included for analysis. EWSR1-NFATc2 fusion positive sarcomas were genomically distinct from traditional Ewing sarcoma and demonstrated upregulation of the mTOR pathway. We also present a case of a 58-year-old male patient with metastatic EWSR1-NFATc2 fusion positive sarcoma who achieved 47 months of disease stabilization when treated with combination mTOR and VEGF inhibition. EWSR1-NFATc2 fusion positive sarcomas are molecularly distinct entities with overactive mTOR signaling; which may be therapeutically targetable. These findings support the use of precision medicine in the Ewing family of tumors.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ritu Pandey ◽  
Muhan Zhou ◽  
Shariful Islam ◽  
Baowei Chen ◽  
Natalie K Barker ◽  
...  

AbstractWe investigated biomarker CEACAM6, a highly abundant cell surface adhesion receptor that modulates the extracellular matrix (ECM) in pancreatic ductal adenocarcinoma (PDA). The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) RNA-Seq data from PDA patients were analyzed for CEACAM6 expression and evaluated for overall survival, association, enrichment and correlations. A CRISPR/Cas9 Knockout (KO) of CEACAM6 in PDA cell line for quantitative proteomics, mitochondrial bioenergetics and tumor growth in mice were conducted. We found CEACAM6 is over-expressed in primary and metastatic basal and classical PDA subtypes. Highest levels are in classical activated stroma subtype. CEACAM6 over-expression is universally a poor prognostic marker in KRAS mutant and wild type PDA. High CEACAM6 expression is associated with low cytolytic T-cell activity in both basal and classical PDA subtypes and correlates with low levels of T-REG markers. In HPAF-II cells knockout of CEACAM6 alters ECM-cell adhesion, catabolism, immune environment, transmembrane transport and autophagy. CEACAM6 loss increases mitochondrial basal and maximal respiratory capacity. HPAF-II CEACAM6−/− cells are growth suppressed by >65% vs. wild type in mice bearing tumors. CEACAM6, a key regulator affects several hallmarks of PDA including the fibrotic reaction, immune regulation, energy metabolism and is a novel therapeutic target in PDA.


1997 ◽  
Vol 24 (8) ◽  
pp. 552-553 ◽  
Author(s):  
Yasuhiko Tamada ◽  
Shouko Arisawa ◽  
Toshihiko Ikeya ◽  
Kazuo Hara

Author(s):  
Matheus del Valle ◽  
Kleber Stancari ◽  
Pedro Arthur Augusto de Castro ◽  
Moises Oliveira dos Santos ◽  
Denise Maria Zezell

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