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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

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Alternative splicing and alternative polyadenylation define tumor immune microenvironment and pharmacogenomic

Weimin Zhong1, Yulong Wu2, Maoshu Zhu1

  • 1Central Laboratory at The Fifth Hospital of Xiamen, Xiamen 361101, Fujian Province, China.

Molecular Therapy. Nucleic Acids
|February 25, 2022
PubMed

Insights

This study reveals how alternative splicing (AS) and alternative polyadenylation (APA) impact clear cell renal cell carcinoma (ccRCC). High AS and APA scores correlate with poor prognosis but may indicate better immunotherapy response.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genomics

Background:

  • Alternative splicing (AS) and alternative polyadenylation (APA) are key posttranscriptional RNA processing events.
  • The roles of AS and APA in clear cell renal cell carcinoma (ccRCC) progression are not well understood.

Purpose of the Study:

  • To investigate the implications of AS and APA events in ccRCC progression.
  • To define AS and APA RNA processing phenotypes in ccRCC.
  • To develop a scoring system to quantify AS and APA patterns in ccRCC.

Main Methods:

  • Consensus molecular clustering analysis to identify AS/APA phenotypes.
  • Principal-component analysis to construct AS/APA scores.
  • Correlation analysis between AS, APA, prognosis, and immune microenvironment.

Main Results:

  • Two distinct AS or APA RNA processing phenotypes were identified, associated with different prognoses, immune cell infiltration, and treatment responses.
  • High AS and APA scores correlated with poorer survival, higher response to immunotherapy, and lower sensitivity to targeted therapies (e.g., sorafenib, pazopanib).
  • A positive correlation between AS and APA scores was observed, with their interplay affecting prognosis and the tumor immune microenvironment.

Conclusions:

  • This is the first comprehensive analysis of AS and APA in ccRCC.
  • AS and APA events play significant roles in ccRCC progression, influencing prognosis and immune evasion.
  • AS and APA patterns offer potential therapeutic targets for immunotherapy and targeted therapy in ccRCC.
Keywords:
alternative polyadenylationalternative splicingclear cell renal carcinomaimmunotherapyprognosistumor microenvironment

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