scholarly journals A Pan-Cancer Analysis of the Prognostic Value and Expression of Adenylate Cyclase 7 (ADCY7) in Human Tumors

2021 ◽  
Vol Volume 14 ◽  
pp. 5415-5429
Author(s):  
Yu Zeng ◽  
Nanhong Li ◽  
Zhenzhen Zheng ◽  
Riken Chen ◽  
Wang Liu ◽  
...  
Bioengineered ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 3634-3646
Author(s):  
Hanyu Zhang ◽  
Cheng Ding ◽  
Yatong Li ◽  
Cheng Xing ◽  
Shunda Wang ◽  
...  

2021 ◽  
Vol 20 ◽  
pp. 117693512110024
Author(s):  
Jason D Wells ◽  
Jacqueline R Griffin ◽  
Todd W Miller

Motivation: Despite increasing understanding of the molecular characteristics of cancer, chemotherapy success rates remain low for many cancer types. Studies have attempted to identify patient and tumor characteristics that predict sensitivity or resistance to different types of conventional chemotherapies, yet a concise model that predicts chemosensitivity based on gene expression profiles across cancer types remains to be formulated. We attempted to generate pan-cancer models predictive of chemosensitivity and chemoresistance. Such models may increase the likelihood of identifying the type of chemotherapy most likely to be effective for a given patient based on the overall gene expression of their tumor. Results: Gene expression and drug sensitivity data from solid tumor cell lines were used to build predictive models for 11 individual chemotherapy drugs. Models were validated using datasets from solid tumors from patients. For all drug models, accuracy ranged from 0.81 to 0.93 when applied to all relevant cancer types in the testing dataset. When considering how well the models predicted chemosensitivity or chemoresistance within individual cancer types in the testing dataset, accuracy was as high as 0.98. Cell line–derived pan-cancer models were able to statistically significantly predict sensitivity in human tumors in some instances; for example, a pan-cancer model predicting sensitivity in patients with bladder cancer treated with cisplatin was able to significantly segregate sensitive and resistant patients based on recurrence-free survival times ( P = .048) and in patients with pancreatic cancer treated with gemcitabine ( P = .038). These models can predict chemosensitivity and chemoresistance across cancer types with clinically useful levels of accuracy.


2021 ◽  
Vol 12 (2) ◽  
pp. 595-610
Author(s):  
Qianyun Ge ◽  
Ganxun Li ◽  
Jin Chen ◽  
Jia Song ◽  
Guangzhen Cai ◽  
...  
Keyword(s):  

2020 ◽  
Vol 89 ◽  
pp. 107080
Author(s):  
Yandong Miao ◽  
Jiangtao Wang ◽  
Qiutian Li ◽  
Wuxia Quan ◽  
Yingying Wang ◽  
...  
Keyword(s):  

2021 ◽  
Vol 11 ◽  
Author(s):  
Huaide Qiu ◽  
Wei Tian ◽  
Yikang He ◽  
Jiahui Li ◽  
Chuan He ◽  
...  

BackgroundCD86 has great potential to be a new target of immunotherapy by regulating cancer immune response. However, it remains unclear whether CD86 is a friend or foe in lower-grade glioma (LGG).MethodsThe prognostic value of CD86 expression in pan-cancer was analyzed using Cox regression and Kaplan-Meier analysis with data from the cancer genome atlas (TCGA). Cancer types where CD86 showed prognostic value in overall survival and disease-specific survival were identified for further analyses. The Chinese Glioma Genome Atlas (CGGA) dataset were utilized for external validation. Quantitative real-time PCR (qRT-PCR), Western blot (WB), and Immunohistochemistry (IHC) were conducted for further validation using surgical samples from Jiangsu Province hospital. The correlations between CD86 expression and tumor immunity were analyzed using the Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm, Tumor IMmune Estimation Resource (TIMER) database, and expressions of immune checkpoint molecules. Gene Set Enrichment Analysis (GSEA) was performed using clusterprofiler r package to reveal potential pathways.ResultsPan-cancer survival analysis established CD86 expression as an unfavorable prognostic factor in tumor progression and survival for LGG. CD86 expression between Grade-II and Grade-III LGG was validated using qRT-PCR and WB. Additionally, CD86 expression in LGG with unmethylated O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter was significantly higher than those with methylated MGMT (P<0.05), while in LGG with codeletion of 1p/19q it was significantly downregulated as opposed to those with non-codeletion (P<2.2*10-16). IHC staining validated that CD86 expression was correlated with MGMT status and X1p/19q subtypes, which was independent of tumor grade. Multivariate regression validated that CD86 expression acts as an unfavorable prognostic factor independent of clinicopathological factors in overall survival of LGG patients. Analysis of tumor immunity and GSEA revealed pivotal role of CD86 in immune response for LGG.ConclusionsIntegrated analysis shows that CD86 is an unfavorable prognostic biomarker in LGG patients. Targeting CD86 may become a novel approach for immunotherapy of LGG.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Neng Tang ◽  
Xiaolin Dou ◽  
Xing You ◽  
Qiman Shi ◽  
Mujing Ke ◽  
...  

Abstract Background In recent years, there have been many studies on the relationship between DLGAP5 and different types of cancers, yet there is no pan-cancer analysis of DLGAP5. Therefore, this study aims to analyze the roles of DLGAP5 in human tumors. Methods Firstly, we evaluated the expression level of DLGAP5 in 33 types of tumors throughout the datasets of TCGA (Cancer Genome Atlas) and GEO (Gene Expression Synthesis). Secondly, we used the GEPIA2 and Kaplan-Meier plotter to conduct Survival prognosis analysis. Additionally, cBioPortal web was utilized to analyze the genetic alteration of DLGAP5, after which we selected hepatocellular carcinoma (HCC) cell lines to define the function of DLGAP5. Last but not least, we performed immune infiltration analysis and DLGAP5-related gene enrichment analysis. Results DLGAP5 is highly expressed in most type of cancers, and there is a significant correlation between the expression of DLGAP5 and the prognosis of cancer patients. We have observed that DLGAP5 promotes the proliferation and invasion of hepatocellular carcinoma (HCC) cell lines. We also found that DLGAP5 expression was related with the CD8+ T-cell infiltration status in kidney renal clear cell carcinoma, uveal melanoma, and thymoma, and cancer-associated fibroblast infiltration was observed in breast invasive carcinoma, kidney renal papillary cell carcinoma and testicular germ cell tumors. In addition, enrichment analysis revealed that cell cycle- and oocyte meiosis-associated functions were involved in the functional mechanism of DLGAP5. Conclusions Taken together, our unpresented pan-cancer analysis of DLGAP5 provides a relatively integrative understanding of the oncogenic role of DLGAP5 in various tumors. DLGAP5 may prompt HCC cellular proliferation, invasion and metastasis. All of these provides solid basement and will promote more advanced understanding the role of DLGAP5 in tumorigenesis and development from the perspective of clinical tumor samples and cells.


2020 ◽  
Author(s):  
Minghui Zhang ◽  
Yanbin Zhao ◽  
Haihong Pu ◽  
Shengyue Guo ◽  
Shuai Zhang ◽  
...  

Abstract Background: CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6) reportedly stabilizes programmed death-ligand 1 (PD-L1) and enhances the efficacy of immunotherapy. However, correlations between CMTM6 expression and the immune microenvironment and its prognostic value remain unknown in a variety of tumors.Methods: CMTM6 expression data were obtained from The Cancer Genome Atlas (TCGA) for 33 cancer types classified into high and low expression subgroups according to the median CMTM6 expression value. Pan-cancer analysis of CMTM6 protein expression in 20 tumor types was performed using a cohort from the Human Protein Atlas (HPA). PD-L1 protein expression data were obtained from The Cancer Proteome Atlas (TCPA) for 32 cancer types. Frequencies of CMTM6 copy number alterations and mutations were analyzed using cBioPortal. MANTIS was employed to estimate microsatellite instability in the TCGA cohort. CIBERSORT and the ESTIMATE algorithm were applied to estimate the relative fractions of infiltrating immune cell types and immune scores, respectively. Kaplan–Meier survival curve analysis was performed to assess the pan-cancer prognostic value of CMTM6.Results: CMTM6 is heterogeneously expressed in diverse cancers. Further, the results revealed low CMTM6 mutation frequencies in multiple cancers. Among them, CMTM6 mutation frequency was the highest in uterine cancer. Additionally, CMTM6 expression was related to PD-L1 protein expression in breast invasive carcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma, cholangiocarcinoma, glioblastoma multiforme (GBM), head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma, sarcoma (SARC), stomach adenocarcinoma, and uterine carcinosarcoma. Increased CMTM6 expression may be associated with increased infiltration of neutrophils in some types of cancer. Finally, pan-cancer analysis indicated that CMTM6 expression was closely related to overall survival in adrenocortical carcinoma, GBM, acute myeloid leukemia, liver hepatocellular carcinoma, mesothelioma, SARC, thymoma, and uveal melanoma. Conclusions: Taken together, these findings highlight that CMTM6 plays an important role in the tumor immune microenvironment, and CMTM6 has been identified to have prognostic value in some types of cancers.Thus, CMTM6 is a potential target for cancer immunotherapy and an effective prognostic biomarker.


2021 ◽  
Author(s):  
Quan Chen ◽  
Chao Jiang ◽  
Jing Li ◽  
Peiqiong Li ◽  
Yekui Yin ◽  
...  

Abstract Background δ-aminolevulinic acid dehydratase (ALAD) is a kind of metalloenzyme, which can catalyze δ-aminolevulinic acid to synthesize bilirubin. However, the expression level, prognostic role, biological function and mechanism of action of ALAD in a variety of human tumors are still not clear. Methods GEPIA Online (http://gepia.cancer-pku.cn) website was used for mRNA analysis of ALAD in multiple human solid tumors. NCBI/GEO database and UALCAN website (http://ualcan.path.uab.edu) were used to analyze the ALAD mRNA expression in breast cancer and lung cancer. Immunohistochemical (IHC) analysis from HPA database was used to detect the protein expression of ALAD in different human tumors. Kaplan-Meier plotter database (http://kmplot.com/analy sis/) was used to evaluate the prognostic value of ALAD expression in different human tumors. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis and Gene Set Enrichment Analysis (GSEA) analysis were used for ALAD enrichment analysis and signal pathway analysis. Results Analyzed by GEPIA, UALCAN online website and GEO analysis in multiple human tumors, the results showed that ALAD mRNA expression is significantly down-regulated and positively correlated with the overall survival (OS) time of different cancer patients. Besides, the expression of ALAD protein is always none or low in multiple solid tumors. In addition, GO and KEGG enrichment analysis suggested that ALAD may play an anti-tumor role in many directions, and GSEA further found that the overexpression of ALAD is negatively correlated with cell cycle signal pathway and PI3K/AKT/mTOR signal pathway. Conclusions In conclusion, our study demonstrated for the first time that ALAD is downregulated in multiple human cancers and ALAD low expression is associated with worse overall survival of different cancer patients. Furthermore, we showed that ALAD low expression is associated with tumor cell cycle process and PI3K/AKT/mTOR signaling pathway. ALAD may be a valuable prognostic biomarker and therapeutic target of multiple human tumors.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Hongshan Ye ◽  
Ning Zhang

Mitochondrial ribosomal protein (MRPL) genes have been reported to participate in many cellular processes, such as cell proliferation, apoptosis, and cell cycle. Meanwhile, the occurrence rate of breast cancer (BRCA) in China steadily increased. Exploring the prognostic value of MRPL genes in BRCA could provide novel biomarkers for BRCA. In this study, to identify prognosis-related genes in breast cancer, the P value and the hazard ratio (HR) of all genes are analyzed with TCGA database. We revealed higher expression level of CEL, PGK1, WNT3A, USP41, LINC02037, PCMT1, LRP11, MCTS1, TCP1, TMEM31, STK4-AS1, STXBP5, LOC100287036, SLC16A2, MRPL13, DERL1, and TARS was correlated to shorter OS time in BRCA. However, higher expression level of JCHAIN, KLRB1, and TNFRSF14 was correlated to longer OS time in BRCA. The further analysis demonstrated MRPL13 was overexpressed in BRCA. Subtype analysis showed that MRPL13 was overexpressed in luminal, HER2-positive BRCA, and TNBC samples and was highest in TNBC samples. Moreover, we revealed higher expression of MRPL13 was significantly correlated to shorter OS time and higher TMB levels in BRCA. Pan-cancer analysis further revealed the prognostic value of MRPL13 in human cancers. MRPL13 expression was significantly increased in multiple human cancers, such as bladder cancer, colon cancer, liver cancer, and prostate cancer. Pan-cancer TMB and overall survival time showed dysregulation of MRPL13 is significantly related to the OS and TMB levels in various cancers. These results further proved that MRPL13 may be a pan-cancer biomarker for predicting prognosis and the response to immunotherapy.


2021 ◽  
Vol 2021 ◽  
pp. 1-23
Author(s):  
Yulan Bu ◽  
Lihua Zhang ◽  
Xiaolin Ma ◽  
Rui Wang ◽  
Xuecheng Zhang ◽  
...  

Background. Emerging studies support the oncogenic role of WD repeat domain 62 (WDR62) in few tumors, while no pan-cancer analysis is available. In this study, we analyzed systematically the oncogenic role of WDR62 across a series of human tumors based on bioinformatic data mining. Methods. The expression level of WDR62 was analyzed via GEPIA2, TIMER, UALCAN, and StarBase databases. The prognostic role was analyzed via GEPIA2, TIMER, UALCAN, StarBase, TISIDB, TCGA portal, Kaplan-Meier Plotter, and PrognoScan databases. Then, we explored the causes for WDR62 abnormal expression via TCGA portal and UALCAN databases. Subsequently, the STRING and GeneMANIA databases were used to find the interactive networks for WDR62. Furthermore, we analyzed the correlation between WDR62 expression and immune features via TIMER and TISIDB databases. Results. We found that WDR62 was significantly upregulated in most of the tumors and correlated with poor prognosis mainly in 6 candidate tumors—BLCA, BRCA, KIRC, KIRP, LIHC, and LUAD. Abnormal WDR62 expression may be probably attributed to TP53 mutation and promoter DNA methylation. Relative network analysis demonstrated that WDR62 was mainly involved in MAPK and toll-like receptor signaling pathway. WDR62 expression was associated with various immune cell infiltrations, especially cancer-associated fibroblasts (CAF) and T cell regulatory (Treg) cells, and was markedly correlated with poor prognosis. Moreover, WDR62 expression was closely associated with the expression of some immunomodulators such as PD-L1 and has a significant prognostic value. Conclusions. Our study revealed that WDR62 could serve as a diagnostic and prognostic biomarker for several cancers. Importantly, WDR62 was closely associated with various immune cell infiltration, and to a certain extent, it can predict the effect of immunotherapy in particular PD1/PD-L1 inhibitors. Our pan-cancer study provided useful information on the oncogenic role of WDR62, contributing to further exploring the underlying mechanisms.


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