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

Our plain-English summary of SHP2 is involved in the occurrence, development and prognosis of cancer, by S. Li, J. Qu, X. Wang, et al (Oncology Letters, 2023).

The study

• Authors: S. Li, J. Qu, X. Wang, Q. Zou, C. Li
• Journal: Oncology Letters
• Published: 2023;26(3):393
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

Copyright: © Li et al.

In plain English

This study did not examine asbestos. Researchers in Chongqing, China, studied a gene called PTPN11, which makes a protein called SHP2, across 33 cancer types in The Cancer Genome Atlas, a public research database. Mesothelioma was one of the 33, but the article does not say whether those tumors were pleural or peritoneal. In each cancer type, patients were split into high- and low-expression groups at the median. In mesothelioma, the high-expression group had shorter overall survival (hazard ratio 1.80; 95% confidence interval 1.23 to 2.22; P=0.027). Mesothelioma could not be compared with normal tissue because the database had no controls for it. Higher expression went with longer survival in kidney renal clear cell carcinoma and with shorter survival in breast, cervical, bladder and liver cancers. In blood tests on local patients, SHP2 was positive more often than in controls in breast and ovarian cancer and less often in endometrial and cervical cancer. The authors concluded that SHP2 expression was related to tumor development and prognosis and that it may be a drug target.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Analysis of public tumor gene-expression data from 33 cancer types (The Cancer Genome Atlas), combined with a laboratory ELISA blood test comparing cancer patients with controls
• Who was studied: Patients with 33 tumor types in The Cancer Genome Atlas, including mesothelioma (the number of patients per tumor type is not given). Also serum samples collected in Chongqing, China, from February 2021 to December 2022: breast cancer 42 vs 42 controls, ovarian cancer 34 vs 36, endometrial cancer 29 vs 33, cervical cancer 46 vs 40
• Exposure: No asbestos or fiber exposure was studied. The factor examined was the expression level of the SHP2/PTPN11 gene, with patients split into high and low groups at the median
• Main results:
  • Of 30 tumor types with normal tissue for comparison, PTPN11 expression was higher in 23 and lower in thymoma, uterine corpus endometrial carcinoma and uterine carcinosarcoma. Mesothelioma, acute myeloid leukemia and uveal melanoma had no normal controls
  • In mesothelioma, the high PTPN11 expression group had shorter overall survival: hazard ratio 1.80, 95% CI 1.23 to 2.22, P=0.027
  • In kidney renal clear cell carcinoma, high PTPN11 expression went with longer overall survival (HR 0.60; 95% CI 0.54 to 0.89; P=0.001)
  • For disease-free survival, high expression went with shorter time in bladder urothelial carcinoma and cervical and endocervical cancer and with longer time in kidney renal clear cell carcinoma. This was not seen in the other tumor types, so no disease-free survival link was reported for mesothelioma
  • In mesothelioma, PTPN11 expression was positively correlated with tumor mutational burden (rho=0.315)
  • In mesothelioma, uterine carcinosarcoma and thyroid carcinoma, PTPN11 expression was negatively correlated with the immune checkpoint gene LAG3. For mesothelioma the table gives rho of minus 0.361, P less than 0.01
  • In several tumor types (not including mesothelioma), PTPN11 expression was negatively correlated with regulatory, follicular helper and CD8+ T cells. In others it was positively correlated with M2 macrophages. These were correlations
  • In blood, SHP2 was positive more often in cancer patients than in controls for breast cancer (30 of 42, 71.43%, vs 8 of 42 controls; odds ratio 10.44) and ovarian cancer (20 of 34, 58.82%, vs 12 of 36 controls; odds ratio 2.92)
  • SHP2 was positive less often in cancer patients than in controls for endometrial cancer (9 of 29, 31.03%, vs 23 of 33 controls) and cervical cancer (19 of 46, 41.30%, vs 26 of 40 controls)
• The authors' conclusion: The authors concluded that SHP2/PTPN11 was widely expressed in most tumors assessed and that its expression was related to tumor development and prognosis. They stated that higher expression could reduce overall survival in bladder, cervical, breast, mesothelioma and liver cancers. They suggested SHP2 may be a target for new cancer drugs

Topics

Medical terms in this study, explained in our Lexicon: Prognosis, Tumor Mutational Burden (TMB), Microsatellite Instability (MSI-H), Tumor Microenvironment, Ovarian Cancer, Overall Survival, Carcinoma, Mesothelioma.

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