Alternative Polyadenylation Regulatory Factors Signature for Survival Prediction in Kidney Renal Cell Carcinoma
View abstract on PubMed
Summary
This summary is machine-generated.Alternative polyadenylation (APA) regulatory factors impact renal cell carcinoma prognosis. A risk score based on five key APA factors predicts patient outcomes and correlates with tumor mutational burden, suggesting a role in immunotherapy response.
Area Of Science
- Molecular Biology
- Oncology
- Genomics
Background
- Alternative polyadenylation (APA) is a crucial regulatory mechanism in disease pathogenesis.
- APA is known to be controlled by specific APA regulatory factors.
Purpose Of The Study
- To investigate the role of APA regulatory factors in the prognosis of renal cell carcinoma (RCC).
- To develop a predictive model for RCC outcomes based on APA regulatory factors.
Main Methods
- Utilized The Cancer Genome Atlas (TCGA) for transcriptome and clinical data.
- Employed Lasso regression to build an APA model for analyzing APA factors in RCC.
- Validated the APA model using independent Gene Expression Omnibus (GEO) datasets (GSE29609, GSE76207).
Main Results
- Identified significant associations between five APA regulatory factors (CPSF1, CPSF2, CSTF2, PABPC1, PABPC4) and tumor mutational burden (TMB) in RCC.
- Developed a risk score using these five factors that effectively predicts RCC patient prognosis.
- Observed that the TMB score is linked to immune microenvironment remodeling.
Conclusions
- Key APA regulatory factors significantly influence the prognosis of renal cell carcinoma patients.
- The developed risk score, associated with TMB, suggests APA's potential role in modulating immunotherapy efficacy via immune microenvironment genes.
- This study enhances understanding of mRNA processing in RCC and its clinical implications.
Related Concept Videos
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...

