Related Experiment Video
Updated: Jul 18, 2025

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
Published on: July 17, 2020
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.
Abstract:
Src homology-2 domain-containing protein tyrosine phosphatase (SHP2), encoded by protein tyrosine phosphatase non-receptor type 11 (PTPN11), is widely expressed in several human tissue types, and plays an important role in a variety of diseases. The present study assessed the impact of SHP2 on the occurrence, development and prognosis of solid tumors. The transcriptome sequencing data of 33 cancer types were downloaded from The Cancer Genome Atlas database. Clinical information of the corresponding patients, tumor mutational burden and information pertinent to microsatellite instability were also downloaded. The log-rank test and univariate Cox's regression test were used to evaluate patient survival. The 'ESTIMATE' method was used to assess the tumor microenvironment, and the 'CIBERSORT' algorithm was used to evaluate tumor immune cell infiltration. Spearman's correlation analysis was used to evaluate the correlation between SHP2 expression and the targets identified. ELISA was used to assess the SHP2 expression levels in peripheral blood samples of patients with breast, ovarian, endometrial and cervical cancer. The data indicated that the expression levels of SHP2 were increased in a variety of tumor tissues, and were associated with tumor progression and prognosis. In peripheral blood, the positive rates of SHP2 expression in breast cancer (71.43%) and ovarian cancer (58.82%) were significantly higher than those in the corresponding control groups. However, the positive rates of SHP2 expression in patients with endometrial cancer (31.03%) and cervical cancer (41.30%) were significantly lower than those in the corresponding control groups. Increased SHP2 expression improved overall survival (OS) and disease free survival (DFS) time in patients with kidney renal clear cell carcinoma. However, increased SHP2 expression reduced OS and DFS in patients with urothelial carcinoma, and cervical and endocervical cancer types. Moreover, the elevated expression of SHP2 could also reduce the OS of patients with breast invasive carcinoma, mesothelioma and liver hepatocellular carcinoma. PTPN11 expression was associated with the tumor microenvironment of various tumor types. The tumor mutational burden of various tumor types was associated with microsatellite instability. PTPN11 inhibited T-cell activation and promoted M2 macrophage activation in several tumors. Therefore, SHP2 may be used in the evaluation of tumor progression and prognosis, and it may be an optimal potential biological target for cancer therapy.
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.
More Related Videos
Related Concept Videos
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Hedgehog Signaling Pathway
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Abnormal Proliferation
Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...

