SHP2 is involved in the occurrence, development and prognosis of cancer

Shu Li1,2, Jialing Qu1,2, Xiaotong Wang3,4

  • 1Department of Clinical Laboratory, Women and Children's Hospital of Chongqing Medical University, Chongqing 401174, P.R. China.

Oncology Letters
|August 21, 2023
PubMed

Insights

Src homology-2 domain-containing protein tyrosine phosphatase (SHP2) impacts solid tumor progression and prognosis. While elevated SHP2 benefits some cancers, it worsens outcomes in others, suggesting it as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Src homology-2 domain-containing protein tyrosine phosphatase (SHP2), encoded by PTPN11, is crucial in cellular signaling and disease.
  • SHP2's role in solid tumor development, progression, and patient prognosis requires comprehensive investigation.

Purpose of the Study:

  • To evaluate the impact of SHP2 expression on the occurrence, development, and prognosis of various solid tumors.
  • To explore the association between SHP2 and the tumor microenvironment, immune cell infiltration, and tumor mutational burden.

Main Methods:

  • Transcriptome sequencing data from The Cancer Genome Atlas (TCGA) for 33 cancer types.
  • Bioinformatic analyses including survival analysis (log-rank, Cox regression), ESTIMATE, CIBERSORT, and Spearman's correlation.
  • ELISA for SHP2 expression in peripheral blood samples of specific cancer patients.

Main Results:

  • SHP2 expression is elevated in numerous tumor tissues and correlates with tumor progression and prognosis.
  • SHP2's prognostic value varies significantly across cancer types; it improves survival in kidney renal clear cell carcinoma but reduces it in urothelial carcinoma, cervical/endocervical, breast invasive carcinoma, mesothelioma, and liver hepatocellular carcinoma.
  • SHP2 expression correlates with the tumor microenvironment, influences T-cell and M2 macrophage activation, and shows associations with tumor mutational burden and microsatellite instability.

Conclusions:

  • SHP2 plays a complex, context-dependent role in solid tumor progression and patient outcomes.
  • SHP2 expression levels can serve as a prognostic biomarker for various cancers.
  • SHP2 represents a promising therapeutic target for cancer treatment, warranting further investigation.

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