scholarly journals A gradient tree boosting and network propagation derived pan-cancer survival network of the tumor microenvironment

iScience ◽  
2021 ◽  
pp. 103617
Author(s):  
Kristina Thedinga ◽  
Ralf Herwig
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Survival ◽  
Network Propagation ◽  
Pan Cancer

scholarly journals Chromosomal copy number heterogeneity predicts survival rates across cancers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Erik van Dijk ◽  
Tom van den Bosch ◽  
Kristiaan J. Lenos ◽  
Khalid El Makrini ◽  
Lisanne E. Nijman ◽  
...  
Keyword(s):  
Copy Number ◽  
Cancer Survival ◽  
Survival Rates ◽  
Cancer Prognosis ◽  
Disease Outcomes ◽  
Distinct Disease ◽  
Cancer Types ◽  
Chromosomal Copy Number ◽  
Chromosomal Copy ◽  
Pan Cancer

AbstractSurvival rates of cancer patients vary widely within and between malignancies. While genetic aberrations are at the root of all cancers, individual genomic features cannot explain these distinct disease outcomes. In contrast, intra-tumour heterogeneity (ITH) has the potential to elucidate pan-cancer survival rates and the biology that drives cancer prognosis. Unfortunately, a comprehensive and effective framework to measure ITH across cancers is missing. Here, we introduce a scalable measure of chromosomal copy number heterogeneity (CNH) that predicts patient survival across cancers. We show that the level of ITH can be derived from a single-sample copy number profile. Using gene-expression data and live cell imaging we demonstrate that ongoing chromosomal instability underlies the observed heterogeneity. Analysing 11,534 primary cancer samples from 37 different malignancies, we find that copy number heterogeneity can be accurately deduced and predicts cancer survival across tissues of origin and stages of disease. Our results provide a unifying molecular explanation for the different survival rates observed between cancer types.

scholarly journals Pan-cancer analysis reveals tumor-associated macrophage communication in the tumor microenvironment

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Linbang Wang ◽  
Tao He ◽  
Jingkun Liu ◽  
Jiaojiao Tai ◽  
Bing Wang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Hub Genes ◽  
Tumor Associated Macrophage ◽  
Molecular Features ◽  
Receptor Interactions ◽  
Tumor Types ◽  
Pan Cancer

Abstract Background Tumor-associated macrophages (TAMs) are abundant in the tumor microenvironment (TME). However, their contribution to the immunosuppressive status of the TME remains unclear. Methods We integrated single-cell sequencing and transcriptome data from different tumor types to uncover the molecular features of TAMs. In vitro experiments and prospective clinical tests confirmed the results of these analysis. Results We first detected intra- and inter-tumoral heterogeneities between TAM subpopulations and their functions, with CD86+ TAMs playing a crucial role in tumor progression. Next, we focused on the ligand-receptor interactions between TAMs and tumor cells in different TME phenotypes and discovered that aberrant expressions of six hub genes, including FLI1, are involved in this process. A TAM-tumor cell co-culture experiment proved that FLI1 was involved in tumor cell invasion, and FLI1 also showed a unique pattern in patients. Finally, TAMs were discovered to communicate with immune and stromal cells. Conclusion We determined the role of TAMs in the TME by focusing on their communication pattern with other TME components. Additionally, the screening of hub genes revealed potential therapeutic targets.

Pan-cancer analysis of ligand-receptor crosstalk in the tumor microenvironment

2021 ◽  
pp. canres.2352.2020
Author(s):  
Umesh Ghoshdastider ◽  
Neha Rohatgi ◽  
Marjan Mojtabavi Naeini ◽  
Probhonjon Baruah ◽  
Egor Revkov ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Receptor Crosstalk ◽  
Pan Cancer

Abstract PO-055: Pan-cancer metabolic profiling of the tumor microenvironment

2020 ◽  
Author(s):  
Neha Rohatgi ◽  
Umesh Ghoshdastider ◽  
Probhonjon Baruah ◽  
Anders Jacobsen Skanderup
Keyword(s):  
Tumor Microenvironment ◽  
Metabolic Profiling ◽  
Pan Cancer

Abstract 1573: Non-canonical NF-kappaB signaling in the tumor microenvironment in relation to ovarian cancer survival

2019 ◽  
Author(s):  
Demetra Hufnagel ◽  
Andrew J. Wilson ◽  
Jamie Saxon ◽  
Timothy Blackwell ◽  
Dineo Khabele ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Cancer Survival ◽  
Nf Kappab ◽  
Ovarian Cancer Survival

scholarly journals A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling

Cell Research ◽  
2020 ◽  
Vol 30 (9) ◽  
pp. 745-762 ◽  
Author(s):  
Junbin Qian ◽  
Siel Olbrecht ◽  
Bram Boeckx ◽  
Hanne Vos ◽  
Damya Laoui ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Single Cell ◽  
Single Cell Profiling ◽  
Pan Cancer ◽  
Heterogeneous Tumor

scholarly journals Pan-Cancer Prognostic, Immunity, Stemness, and Anticancer Drug Sensitivity Characterization of N6-Methyladenosine RNA Modification Regulators in Human Cancers

2021 ◽  
Vol 8 ◽  
Author(s):  
Rui Li ◽  
Yun-Hong Yin ◽  
Xiu-Li Ji ◽  
Xiao Liu ◽  
Jian-Ping Li ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Anticancer Drug ◽  
Drug Sensitivity ◽  
Rna Modification ◽  
Immune Microenvironment ◽  
Normal Tissues ◽  
Tumor Immune Microenvironment ◽  
Cancer Types ◽  
Pan Cancer

N6-methyladenosine RNA modification plays a significant role in the progression of multiple tumorigenesis. Our study identified the imperative role of m6A regulators in the tumor immune microenvironment, survival, stemness score, and anticancer drug sensitivity of pan-cancer. The Wilcox test was to identify the differential expression between 17 m6A regulators across 33 TCGA cancer types and their normal tissues from UCSC Xena GDC pan-cancer. Survival analysis of m6A-related regulators in 33 TCGA cancer types was identified using the “survival” and “survminer” package. The Spearman correlation test and Pearson correlation test were used to identify the correlation relationship between m6A regulators expression and tumor microenvironment, tumor stem cell score, and drug sensitivity of anticancer drugs. ConsensusPathDB was used for exploring m6A regulators functional enrichment. The 17 (METTL3, WTAP, METTL14, RBM15, RBM15B, VIRMA, HNRNPC, HNRNPA2B1, YTHDC1, ZC3H13, YTHDF1, YTHDC2, YTHDF2, IGF2BP3, IGF2BP1, FTO, and ALKBH5) m6A regulators were differentially expressed in 18 TCGA cancer types and adjacent normal tissues. Correlation analysis indicated that the relationship between the expression of 17 m6A regulators and tumor microenvironment indicated that the higher expression of m6A regulators, the higher the degree of tumor stem cells. The anticancer drug sensitivity analysis indicated that ZC3H13 expression had a positive relationship with anticancer drugs such as selumetinib, dabrafenib, cobimetinib, trametinib, and hypothemycin (p < 0.001). YTHDF2 expression was significantly negatively correlated with the anticancer drug dasatinib (p < 0.001). The pan-cancer immune subtype analysis showed that the 17 m6A regulators were significantly different in immune subtype C1 (wound healing), C3 (inflammatory), C2 (IFN-gamma dominant), C5 (immunological quiet), C4 (lymphocyte depleted), and C6 (TGF-beta dominant) (p < 0.001). Our study provides a comprehensive insight for revealing the significant role of m6A regulators in the tumor immune microenvironment, stemness score, and anticancer drug sensitivity of human cancers.

scholarly journals A Pan-cancer Analysis of the Prognostic and Immunological Role of PPP1R14A

2021 ◽  
Author(s):  
JiaJie Lu ◽  
Rihong Huang ◽  
Haojian Wang ◽  
Yuecheng Peng ◽  
Yongyang Fan ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Cancer Survival ◽  
Malignant Tumors ◽  
Genetic Alterations ◽  
Poor Overall Survival ◽  
Carcinogenic Effect ◽  
Genetic Changes ◽  
Pan Cancer

Abstract BackgroundDespite emerging evidence revealed the remarkable roles of Protein Phosphatase 1 Regulatory Inhibitor Subunit 14A (PPP1R14A) in cancer tumorigenesis and progression, no pan-cancer analysis is available. Our research, for the first time, comprehensively investigated the potential carcinogenic mechanism of PPP1R14A across 33 tumors using bioinformatic techniques. MethodsTCGA datasets and the CPTAC datasets embedded in UALCAN were first applied to study the differential expression of PPP1R14A in various cancer types at the transcription and protein levels, respectively. Besides, we also conducted relevant prognostic survival analysis and used the GEPIA2 database to explore the association between PPP1R14A expression and pathological stages. In addition, cBioPortal and UALCAN databases were employed to analyze the genetic alterations and post-transcriptional phosphorylation of PPP1R14A. Then based on TCGA, we analyzed the relationship between PPP1R14A and immune infiltration, the correlation with tumor mutational burden (TMB), microsatellite instability (MSI) and immune checkpoint molecules (ICMs), and whether it is expected to be a predictive indicator in cancer patients, which was achieved by receiver operating characteristic (ROC) curve. Finally, STRING, GEPIE2 and TIMER2.0 databased were used to explore the potential mechanism of PPP1R14A in cancer and find molecules that have potential close interactions with PPP1R14A.ResultsPPP1R14A is down-expressed in major malignancies and there is a significant correlation between the PPP1R14A expression and the prognosis of patients. Pan-cancer survival analysis indicated that the high expression of PPP1R14A in most cases was associated with poor overall survival (OS), disease-specific survival (DSS), and progress-free interval (PFI) across patients with various malignant tumors, containing adrenocortical carcinoma (ACC), bladder urothelial carcinoma (BLCA). The results of ROC analysis subsequently exhibited that the molecule has a high reference significance in diagnosing a variety of cancers. Besides, we detected that the frequency of PPP1R14A genetic changes including genetic mutations and copy number alterations (CNAs) in uterine carcinosarcoma reached 16.07%, and these alterations brought misfortune to the survival and prognosis of cancer patients. In addition, the methylation within the promoter region of PPP1R14A DNA was enhanced in a majority of cancers. Downregulated phosphorylation levels of phosphorylation sites including S26, T38, etc. in most cases took place in several tumors, such as breast cancer, colon cancer, etc. PPP1R14A remarkably correlated with the levels of infiltrating cells and immune checkpoint genes. ConclusionsOur research summarized and analyzed the carcinogenic effect of PPP1R14A in different tumors comprehensively and provided a theoretical basis for promising therapeutic and immunotherapy strategies.

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