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Article Open Access

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

  • Authors:
    • Shu Li
    • Jialing Qu
    • Xiaotong Wang
    • Qin Zou
    • Chunli Li
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Laboratory, Women and Children's Hospital of Chongqing Medical University, Chongqing 401174, P.R. China, Department of Clinical Laboratory, Chongqing Health Center for Women and Children, Chongqing 401174, P.R. China, Department of Obstetrics and Gynecology, Women and Children's Hospital of Chongqing Medical University, Chongqing 401174, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 393
    |
    Published online on: July 27, 2023
       https://doi.org/10.3892/ol.2023.13979
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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.
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1 

Yuan H, Zhao J, Yang Y, Wei R, Zhu L, Wang J, Ding M, Wang M and Gu Y: SHP-2 Interacts with CD81 and regulates the malignant evolution of colorectal cancer by inhibiting epithelial-mesenchymal transition. Cancer Manag Res. 12:13273–13284. 2020. View Article : Google Scholar : PubMed/NCBI

2 

Zhou L, Feng Y, Ma YC, Zhang Z, Wu JW, Du S, Li WY, Lu XH, Ma Y and Wang RL: Exploring the mechanism of the potent allosteric inhibitor compound2 on SHP2WT and SHP2F285S by molecular dynamics study. J Mol Graph Model. 103:1078072021. View Article : Google Scholar : PubMed/NCBI

3 

Mitra R and Ayyannan SR: Small-Molecule Inhibitors of Shp2 phosphatase as potential chemotherapeutic agents for Glioblastoma: A Minireview. ChemMedChem. 16:777–787. 2021. View Article : Google Scholar : PubMed/NCBI

4 

Li S, Wang X, Li Q and Li C: Role of SHP2/PTPN11 in the occurrence and prognosis of cancer: A systematic review and meta-analysis. Oncol Lett. 25:192023. View Article : Google Scholar : PubMed/NCBI

5 

Kim JS, Shin OR, Kim HK, Cho YS, An CH, Lim KW and Kim SS: Overexpression of protein phosphatase non-receptor type 11 (PTPN11) in gastric carcinomas. Dig Dis Sci. 55:1565–1569. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Kerr DL, Haderk F and Bivona TG: Allosteric SHP2 inhibitors in cancer: Targeting the intersection of RAS, resistance, and the immune microenvironment. Curr Opin Chem Biol. 62:1–12. 2021. View Article : Google Scholar : PubMed/NCBI

7 

Sausgruber N, Coissieux MM, Britschgi A, Wyckoff J, Aceto N, Leroy C, Stadler MB, Voshol H, Bonenfant D and Bentires-Alj M: Tyrosine phosphatase SHP2 increases cell motility in triple-negative breast cancer through the activation of SRC-family kinases. Oncogene. 34:2272–2278. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Mainardi S, Mulero-Sánchez A, Prahallad A, Germano G, Bosma A, Krimpenfort P, Lieftink C, Steinberg JD, de Wit N, Gonçalves-Ribeiro S, et al: SHP2 is required for growth of KRAS-mutant non-small-cell lung cancer in vivo. Nat Med. 24:961–967. 2018. View Article : Google Scholar : PubMed/NCBI

9 

Jiang C, Hu F, Tai Y, Du J, Mao B, Yuan Z, Wang Y and Wei L: The tumor suppressor role of Src homology phosphotyrosine phosphatase 2 in hepatocellular carcinoma. J Cancer Res Clin Oncol. 138:637–646. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Xinhua S: Role of CAD gene in the prognosis evaluation of pan-cancer. J Basic Clinical Oncol. 33:485–90. 2020.

11 

Zhang Z, Lin E, Zhuang H, Xie L, Feng X, Liu J and Yu Y: Construction of a novel gene-based model for prognosis prediction of clear cell renal cell carcinoma. Cancer Cell Int. 20:272020. View Article : Google Scholar : PubMed/NCBI

12 

Sturm G, Finotello F, Petitprez F, Zhang JD, Baumbach J, Fridman WH, List M and Aneichyk T: Comprehensive evaluation of transcriptome-based cell-type quantification methods for immuno-oncology. Bioinformatics. 35:i436–i45. 2019. View Article : Google Scholar : PubMed/NCBI

13 

Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang TH, Porta-Pardo E, Gao GF, Plaisier CL, Eddy JA, et al: The Immune landscape of cancer. Immunity. 51:411–412. 2019. View Article : Google Scholar : PubMed/NCBI

14 

Gu J, Han T, Ma RH, Zhu YL, Jia YN, Du JJ, Chen Y, Jiang XJ, Xie XD and Guo X: SHP2 promotes laryngeal cancer growth through the Ras/Raf/Mek/Erk pathway and serves as a prognostic indicator for laryngeal cancer. Int J Oncol. 44:481–490. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Chalfant CE, Kim M, Hartman Z, Geldenhuys WJ and Agazie YM: Novel Small-molecule inhibitor for the oncogenic tyrosine phosphatase SHP2 with anti-breast cancer cell effects. Mol Cancer Res. 5:25113–25124. 2020.

16 

Vazhappilly CG, Saleh E, Ramadan W, Menon V, Al-Azawi AM, Tarazi H, Abdu-Allah H, El-Shorbagi AN and El-Awady R: Inhibition of SHP2 by new compounds induces differential effects on RAS/RAF/ERK and PI3K/AKT pathways in different cancer cell types. Invest New Drugs. 37:252–261. 2019. View Article : Google Scholar : PubMed/NCBI

17 

Ahmed TA, Adamopoulos C, Karoulia Z, Wu X, Sachidanandam R, Aaronson SA and Poulikakos PI: SHP2 Drives adaptive resistance to ERK signaling inhibition in molecularly defined subsets of ERK-Dependent tumors. Cell Rep. 26:65–78.e5. 2019. View Article : Google Scholar : PubMed/NCBI

18 

Fedele C, Ran H, Diskin B, Wei W, Jen J, Geer MJ, Araki K, Ozerdem U, Simeone DM, Miller G, et al: SHP2 inhibition prevents adaptive resistance to MEK inhibitors in multiple cancer models. Cancer Discov. 8:1237–1249. 2018. View Article : Google Scholar : PubMed/NCBI

19 

Feng HB, Chen Y, Xie Z, Jiang J, Zhong YM, Guo WB, Yan WQ, Lv ZY, Lu DX, Liang HL, et al: High SHP2 expression determines the efficacy of PD-1/PD-L1 inhibitors in advanced KRAS mutant non-small cell lung cancer. Thorac Cancer. 12:2564–2573. 2021. View Article : Google Scholar : PubMed/NCBI

20 

Lei W, Qin X, Wang X and Zhu F: Expression and clinical significance of Shp2 protein in breast cancer. Jilin Med J. 32:7692–7694. 2011.

21 

Hu Z, Li J, Gao Q, Wei S and Yang B: SHP2 overexpression enhances the invasion and metastasis of ovarian cancer in vitro and in vivo. Onco Targets Ther. 10:3881–3891. 2017. View Article : Google Scholar : PubMed/NCBI

22 

Liotti F, Kumar N, Prevete N, Marotta M, Sorriento D, Ieranò C, Ronchi A, Marino FZ, Moretti S, Colella R, et al: PD-1 blockade delays tumor growth by inhibiting an intrinsic SHP2/Ras/MAPK signalling in thyroid cancer cells. J Exp Clin Cancer Res. 40:222021. View Article : Google Scholar : PubMed/NCBI

23 

Zhao Y, Yu H, Ida CM, Halling KC, Kipp BR, Geiersbach K, Rumilla KM, Gupta S, Lin MT and Zheng G: Assessment of RAS dependency for BRAF alterations using cancer genomic databases. JAMA Netw Open. 4:e20354792021. View Article : Google Scholar : PubMed/NCBI

24 

Yuan X, Bu H and Zhou J: Recent advances of SHP2 inhibitors in cancer therapy: Current development and clinical application. J Med Chem. 63:11368–11396. 2020. View Article : Google Scholar : PubMed/NCBI

25 

Kim M, Morales LD and Jang IS: Protein tyrosine phosphatases as potential regulators of STAT3 signaling. Int J Mol Sci. 19:27082018. View Article : Google Scholar : PubMed/NCBI

26 

Zhang W, Chan RJ, Chen H, Yang Z, He Y, Zhang X, Luo Y, Yin F, Moh A, Miller LC, et al: Negative regulation of Stat3 by activating PTPN11 mutants contributes to the pathogenesis of Noonan syndrome and juvenile myelomonocytic leukemia. J Biol Chem. 284:22353–22363. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Wang J, Pollard K, Allen AN, Tomar T, Pijnenburg D, Yao Z and Rodriguez FJ: Combined inhibition of SHP2 and MEK is effective in models of NF1-Deficient malignant peripheral nerve sheath tumors. Cancer Res. 80:5367–5379. 2020. View Article : Google Scholar : PubMed/NCBI

28 

Zhu G, Xie J, Kong W, Xie J, Li Y, Du L, Zheng Q, Sun L, Guan M, Li H, et al: Phase separation of disease-associated SHP2 mutants underlies MAPK hyperactivation. Cell. 183:490–502.e18. 2020. View Article : Google Scholar : PubMed/NCBI

29 

Gong M, Liu P, He T, Zhang M and Li G: Demonstrating the effect of SHP2 inhibitor on cervical squamous cell carcinoma from the perspective of ZAP70. Anticancer Drugs. 32:477–483. 2021. View Article : Google Scholar : PubMed/NCBI

30 

Cassetta L and Pollard JW: Targeting macrophages: Therapeutic approaches in cancer. Nat Rev Drug Discov. 17:887–904. 2018. View Article : Google Scholar : PubMed/NCBI

31 

Xiao P, Zhang H, Zhang Y, Zheng M, Liu R, Zhao Y, Zhang X, Cheng H, Cao Q and Ke Y: Phosphatase Shp2 exacerbates intestinal inflammation by disrupting macrophage responsiveness to interleukin-10. J Exp Med. 216:337–349. 2019. View Article : Google Scholar : PubMed/NCBI

32 

Hui E, Cheung J, Zhu J, Su X, Taylor MJ, Wallweber HA, Sasmal DK, Huang J, Kim JM, Mellman I and Vale RD: T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition. Science. 355:1428–1433. 2017. View Article : Google Scholar : PubMed/NCBI

33 

Torres-Ayuso P and Brognard J: Shipping out MEK inhibitor resistance with SHP2 inhibitors. Cancer Discov. 8:1210–1212. 2018. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Li S, Qu J, Wang X, Zou Q and Li C: SHP2 is involved in the occurrence, development and prognosis of cancer. Oncol Lett 26: 393, 2023.
APA
Li, S., Qu, J., Wang, X., Zou, Q., & Li, C. (2023). SHP2 is involved in the occurrence, development and prognosis of cancer. Oncology Letters, 26, 393. https://doi.org/10.3892/ol.2023.13979
MLA
Li, S., Qu, J., Wang, X., Zou, Q., Li, C."SHP2 is involved in the occurrence, development and prognosis of cancer". Oncology Letters 26.3 (2023): 393.
Chicago
Li, S., Qu, J., Wang, X., Zou, Q., Li, C."SHP2 is involved in the occurrence, development and prognosis of cancer". Oncology Letters 26, no. 3 (2023): 393. https://doi.org/10.3892/ol.2023.13979
Copy and paste a formatted citation
x
Spandidos Publications style
Li S, Qu J, Wang X, Zou Q and Li C: SHP2 is involved in the occurrence, development and prognosis of cancer. Oncol Lett 26: 393, 2023.
APA
Li, S., Qu, J., Wang, X., Zou, Q., & Li, C. (2023). SHP2 is involved in the occurrence, development and prognosis of cancer. Oncology Letters, 26, 393. https://doi.org/10.3892/ol.2023.13979
MLA
Li, S., Qu, J., Wang, X., Zou, Q., Li, C."SHP2 is involved in the occurrence, development and prognosis of cancer". Oncology Letters 26.3 (2023): 393.
Chicago
Li, S., Qu, J., Wang, X., Zou, Q., Li, C."SHP2 is involved in the occurrence, development and prognosis of cancer". Oncology Letters 26, no. 3 (2023): 393. https://doi.org/10.3892/ol.2023.13979
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