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  4. Identification of Prognostic and Metastatic Alternative Splicing Signatures in Kidney Renal Clear Cell Carcinoma

Identification of Prognostic and Metastatic Alternative Splicing Signatures in Kidney Renal Clear Cell Carcinoma

Frontiers in Bioengineering and Biotechnology, 2019 · DOI: 10.3389/fbioe.2019.00270 · Published: October 15, 2019

OncologyBioinformatics

Simple Explanation

This study explores the role of alternative splicing events (ASEs) in the development and spread (metastasis) of kidney renal clear cell carcinoma (KIRC). The aim of this study is to explore the mechanism of alternative splicing events (ASEs) underlying tumorigenesis and metastasis of KIRC. Researchers analyzed RNA sequencing data from KIRC samples to identify ASEs linked to patient survival and metastasis. Additionally, metastasis-related ASEs along with corresponding SFs and pathways were also identified by Pearson correlation analysis to illuminate the underlying mechanism of metastasis in KIRC. The study identified specific splicing factors and genes (RHOT2, TCIRG1) that may play a role in KIRC metastasis, which could lead to new treatment targets. Aberrant DDX39B regulated RHOT2-32938-RI and TCIRG1-17288-RI might be related to the tumorigenesis, metastasis and poor prognosis of KIRC via sphingolipid metabolism or N-glycan biosynthesis pathway.

Study Duration
Not specified
Participants
537 KIRC samples
Evidence Level
Not specified

Key Findings

  • 1
    Identified 6,081 overall survival-related ASEs (OS-SEs) in KIRC. A total of prognostic 6,081 overall survival-related ASEs (OS-SEs) were identified by univariate Cox regression analysis
  • 2
    Developed a prediction model based on 5 OS-SEs with an AUC of 0.788, showing good reliability. a prediction model was constructed based on 5 OS-SEs screened by Lasso regression with the Area Under Curve of 0.788.
  • 3
    DDX39B was identified as a significant splicing factor correlated with OS and metastasis. Among 390 identified candidate SFs, DExD-Box Helicase 39B (DDX39B) was significantly correlated with OS and metastasis.

Research Summary

This study aimed to identify alternative splicing events (ASEs) associated with prognosis and metastasis in kidney renal clear cell carcinoma (KIRC) using bioinformatic analysis of TCGA data. In this study, we performed a comprehensive analysis of AS profiling to identify the overall survival-related ASEs (OS- SEs) in patients with KIRC and construct a prognostic model. The analysis identified thousands of OS-SEs, constructed a prognostic model based on 5 key ASEs, and highlighted DDX39B as a significant splicing factor correlated with both overall survival and metastasis. The prediction model might assist oncologists in clinical decision-making. The study proposes that aberrant DDX39B regulation of RHOT2 and TCIRG1 splicing might contribute to KIRC tumorigenesis, metastasis, and poor prognosis through sphingolipid metabolism or N-glycan biosynthesis. Based on the comprehensive bioinformatics analysis, we proposed that aberrant DDX39B regulated RHOT2-32938-RI and TCIRG1- 17288-RI might be related to the tumorigenesis, metastasis and poor prognosis of KIRC

Practical Implications

Prognostic Prediction

The developed prediction model could help oncologists in clinical decision-making for KIRC patients.

Therapeutic Targets

RHOT2 and TCIRG1 could be potential therapeutic targets for KIRC metastasis, especially bone metastasis.

Mechanistic Insights

The study sheds light on the role of sphingolipid metabolism and N-glycan biosynthesis in KIRC tumorigenesis and metastasis.

Study Limitations

  • 1
    Pure bioinformatics study without biological experiments.
  • 2
    Sequencing data from a single cohort with a limited sample size.
  • 3
    Lack of samples from metastatic sites (lung, bone, brain).

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