Analysis of TERT Isoforms across TCGA, GTEx and CCLE Datasets

Subasri, Mathushan; Shooshtari, Parisa; Watson, Andrew J.; Betts, Dean H.

doi:10.3390/cancers13081853

Cited by 6 publications

(5 citation statements)

References 114 publications

(94 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, as the research on telomerase [ 2 ] and alternative lengthening of telomeres [ 3 ] in human cancer is being actively conducted, interest in the role of TMM in the immortality of tumor cells (which is one of the hallmarks of cancer) is increasing. It has also been studied in cancer cell lines with tumors of relevant origin based on TERT isoform expression patterns [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Pan-Cancer Analysis of Clinical Relevance via Telomere Maintenance Mechanism

Sung

Cheong

2021

IJMS

View full text Add to dashboard Cite

Understanding the telomere maintenance mechanism (TMM) in immortal cancer cells is vital for TMM-targeted therapies in clinical settings. In this study, we classified four telomere maintenance mechanisms into telomerase, ALT, telomerase + ALT, and non-defined telomere maintenance mechanism (NDTMM) across 31 cancer types using 10,704 transcriptomic datasets from The Cancer Genome Atlas. Our results demonstrated that approximately 50% of the total cohort displayed ALT activity with high telomerase activity in most cancer types. We confirmed significant patient prognoses according to distinct TMMs in six cancer types: adrenocortical carcinoma (ACC), PAAD, HNSC, SARC, GBM, and metastatic cancer. Patients with metastasis had a poor prognosis in the ALT group (p < 0.006) subjected to RAS protein signal transduction. Glioblastoma patients had poor prognosis in NDTMM (p < 0.0043) and showed high levels of myeloid leukocyte activation. Pancreatic adenocarcinoma (p < 0.04) and head and neck squamous cell carcinoma (p < 0.046) patients had a good prognosis in the ALT group with high immune cell activation. Furthermore, we showed that master transcriptional regulators might affect the selection of the TMM pathway and explained why different telomere maintenance mechanisms exist. Furthermore, they can be used to segregate patients and predict responders to different TMM-targeted therapeutics.

show abstract

Section: Introductionmentioning

confidence: 99%

Pan-Cancer Analysis of Clinical Relevance via Telomere Maintenance Mechanism

Sung

Cheong

2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Based on the Cancer Genome Atlas (TCGA) and the Genotype‐Tissue Expression (GTEx) data of 33 cancers, the clinical data of overall survival (OS), disease‐free interval (DFI), progression‐free interval (PFI), disease‐specific survival (DSS) for each TCGA cancer type and TCGA pan‐cancer immune phenotype data were downloaded from the USCS Xena browser (https://xenabrowser.net/datapages/)). Although the TCGA project also included the sequencing data of adjacent normal tissue samples from some patients, these “normal” tissue samples may be affected by neighboring tumor cells, which is why GETx samples were applied to match normal tissue 22,23 . Therefore, we used the “ComBat” function of the “sva” package to correct for the nonbiological batch effects of the standardized RNA‐seq between TCGA and GTEx.…”

Section: Methodsmentioning

confidence: 99%

“…Although the TCGA project also included the sequencing data of adjacent normal tissue samples from some patients, these “normal” tissue samples may be affected by neighboring tumor cells, which is why GETx samples were applied to match normal tissue. 22 , 23 Therefore, we used the “ComBat” function of the “sva” package to correct for the nonbiological batch effects of the standardized RNA‐seq between TCGA and GTEx. The R software was used to extract the expression matrix of IGFBPs.…”

Section: Methodsmentioning

confidence: 99%

Pan‐cancer analysis of oncogenic role of insulin‐like growth factor‐binding proteins and validation in ovarian cancer

et al. 2023

View full text Add to dashboard Cite

Background Numerous studies have shown that the insulin‐like growth factor (IGF) pathway is highly associated with tumor initial and progression in several tumors. However, compared with IGF1/1R and IGF2/2R, insufficient studies have focused on IGF‐binding proteins (IGFBPs). Methods The GDC TCGA and GTEx data of 33 cancers, TCGA pan‐cancer immune phenotypes, tumor mutation burdens, and the copy number alterations of IGFBPs were extracted. Next, the prognostic value of IGFBPs was analyzed based on a univariate Cox analysis. Additionally, the ESTIMATE algorithm was used to calculate stromal and immune scores and tumor purity, and the CIBERSORT algorithm was used to estimate tumor‐infiltrating immunocyte levels. Ultimately, the correlation between IGFBP expression and cancer hallmark pathways was estimated with a Spearman analysis. Results The expression of IGFBPs was differentially expressed and correlated with prognosis in specific cancers. IGFBPs may operate as biological markers for carcinogenesis and progression and as prognostic biomarkers. Additionally, IGFBP5 has been proved that promotes the invasion and migration of ovarian cancer. Conclusions In general, IGFBPs can serve as predictable biomarkers and potential therapeutic targets for specific tumors. Our results could provide underlying targets for the design of laboratory experiments to elucidate the mechanism of IGFBPs in cancers and identify IGFBP5 as a prognostic factor in ovarian cancers.

show abstract

“…In normal cells, telomeres gradually shorten with each cell division, leading to cell cycle arrest or apoptosis [ 8 ]. However, tumor cells employ unique mechanisms like telomerase activation and telomerase-independent alternative lengthening telomeres for maintenance [ 9 , 10 ]. Studies have demonstrated that telomere length changes and maintenance have been linked to tumor survival, proliferation, metastasis, and poor clinical outcomes in various cancers, including PRAD [ 11 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

Predicting prostate adenocarcinoma patients’ survival and immune signature: a novel risk model based on telomere-related genes

Zheng,

Chen,

et al. 2024

Discov Onc

View full text Add to dashboard Cite

Alterations in telomeres constitute some of the earliest occurrences in the tumourigenesis of prostate adenocarcinoma (PRAD) and persist throughout the progression of the tumour. While the activity of telomerase and the length of telomeres have been demonstrated to correlate with the prognosis of PRAD, the prognostic potential of telomere-related genes (TRGs) in this disease remains unexplored. Utilising mRNA expression data from the Cancer Genome Atlas (TCGA), we devised a risk model and a nomogram to predict the survival outcomes of patients with PRAD. Subsequently, our investigations extended to the relationship between the risk model and immune cell infiltration, sensitivity to chemotherapeutic drugs, and specific signalling pathways. The risk model we developed is predicated on seven key TRGs, and immunohistochemistry results revealed significant differential expression of three TRGs in tumours and paracancerous tissues. Based on the risk scores, PRAD patients were stratified into high-risk and low-risk cohorts. The Receiver operating characteristics (ROC) and Kaplan–Meier survival analyses corroborated the exceptional predictive performance of our novel risk model. Multivariate Cox regression analysis indicated that the risk score was an independent risk factor associated with Overall Survival (OS) and was significantly associated with T and N stages of PRAD patients. Notably, the high-risk group exhibited a greater response to chemotherapy and immunosuppression compared to the low-risk group, offering potential guidance for treatment strategies for high-risk patients. In conclusion, our new risk model, based on TRGs, serves as a reliable prognostic indicator for PRAD. The model holds significant value in guiding the selection of immunotherapy and chemotherapy in the clinical management of PRAD patients.

show abstract

Analysis of TERT Isoforms across TCGA, GTEx and CCLE Datasets

Cited by 6 publications

References 114 publications

Pan-Cancer Analysis of Clinical Relevance via Telomere Maintenance Mechanism

Pan-Cancer Analysis of Clinical Relevance via Telomere Maintenance Mechanism

Pan‐cancer analysis of oncogenic role of insulin‐like growth factor‐binding proteins and validation in ovarian cancer

Predicting prostate adenocarcinoma patients’ survival and immune signature: a novel risk model based on telomere-related genes

Contact Info

Product

Resources

About