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Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer

  • Authors:
    • Satoshi Inoue
    • Takumi Tsunoda
    • Miho Riku
    • Hideaki Ito
    • Akihito Inoko
    • Hideki Murakami
    • Masahide Ebi
    • Naotaka Ogasawara
    • Ira Pastan
    • Kunio Kasugai
    • Kenji Kasai
    • Hiroshi Ikeda
    • Shingo Inaguma
  • View Affiliations / Copyright

    Affiliations: Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480‑1195, Japan, Department of Pathology, Aichi Medical University School of Medicine, Nagakute 480‑1195, Japan, Aichi Medical University School of Medicine, Nagakute 480‑1195, Japan, Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA
    Copyright: © Inoue et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1741-1750
    |
    Published online on: January 10, 2020
       https://doi.org/10.3892/ol.2020.11290
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Abstract

Mesothelin (MSLN) is a glycophosphatidylinositol (GPI)‑linked cell surface protein that is highly expressed in several types of malignant tumor, including malignant pleural mesothelioma, ovarian cancer and pancreatic adenocarcinoma. Recently, a comprehensive immunohistochemical study using MN‑1 monoclonal antibody identified a significant number of colorectal tumors in which MSLN was expressed. However, the clinicopathological profiles and survival of patients with MSLN‑positive colorectal cancer have not been fully analyzed. In the current study, the expression of MSLN in 270 primary and 44 metastatic colorectal tumors was immunohistochemically analyzed to determine the clinical usefulness of MSLN immunohistochemistry and to identify potential candidates for future anti‑MSLN therapy. In vitro experiments using colon cancer cell lines were performed to investigate the biological significance of MSLN expression in tumors. The results of univariate analyses identified a significant correlation between MSLN expression and females (P=0.0042). Furthermore, an inverse correlation between MSLN expression and solid/sheet‑like proliferation (P=0.014) was also revealed. Additionally, overall survival was significantly shorter in patients with diffuse luminal/membranous expression of MSLN (P=0.018). Multivariable Cox hazards regression analysis revealed diffuse MSLN expression (hazard ratio, 2.26; 95% confidence interval, 1.04‑4.91; P=0.039) as a potential risk factor. When comparing primary CRCs and the metastasis of each, a weakly positive correlation was identified for MSLN positivity (% positive cells; R=0.484; P<0.0001). The in vitro experiments revealed a positive role for MSLN in colon cancer cell proliferation. Thus, MSLN immunohistochemistry may be useful in the prognostication of patients with CRC. The results demonstrated that significant numbers of patients with MSLN‑positive CRC exhibiting metastasis could be targeted by anti‑MSLN therapies.
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1 

Chang K and Pastan I: Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers. Proc Natl Acad Sci USA. 93:136–140. 1996. View Article : Google Scholar : PubMed/NCBI

2 

Bera TK and Pastan I: Mesothelin is not required for normal mouse development or reproduction. Mol Cell Biol. 20:2902–2906. 2000. View Article : Google Scholar : PubMed/NCBI

3 

Chang K, Pai LH, Pass H, Pogrebniak HW, Tsao MS, Pastan I and Willingham MC: Monoclonal antibody K1 reacts with epithelial mesothelioma but not with lung adenocarcinoma. Am J Surg Pathol. 16:259–268. 1992. View Article : Google Scholar : PubMed/NCBI

4 

Hassan R, Kreitman RJ, Pastan I and Willingham MC: Localization of mesothelin in epithelial ovarian cancer. Appl Immunohistochem Mol Morphol. 13:243–247. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Hassan R, Laszik ZG, Lerner M, Raffeld M, Postier R and Brackett D: Mesothelin is overexpressed in pancreaticobiliary adenocarcinomas but not in normal pancreas and chronic pancreatitis. Am J Clin Pathol. 124:838–845. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Miettinen M and Sarlomo-Rikala M: Expression of calretinin, thrombomodulin, keratin 5, and mesothelin in lung carcinomas of different types: An immunohistochemical analysis of 596 tumors in comparison with epithelioid mesotheliomas of the pleura. Am J Surg Pathol. 27:150–158. 2003. View Article : Google Scholar : PubMed/NCBI

7 

Ordonez NG: Application of mesothelin immunostaining in tumor diagnosis. Am J Surg Pathol. 27:1418–1428. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Kachala SS, Bograd AJ, Villena-Vargas J, Suzuki K, Servais EL, Kadota K, Chou J, Sima CS, Vertes E, Rusch VW, et al: Mesothelin overexpression is a marker of tumor aggressiveness and is associated with reduced recurrence-free and overall survival in early-stage lung adenocarcinoma. Clin Cancer Res. 20:1020–1028. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Thomas A, Chen Y, Steinberg SM, Luo J, Pack S, Raffeld M, Abdullaev Z, Alewine C, Rajan A, Giaccone G, et al: High mesothelin expression in advanced lung adenocarcinoma is associated with KRAS mutations and a poor prognosis. Oncotarget. 6:11694–11703. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Einama T, Homma S, Kamachi H, Kawamata F, Takahashi K, Takahashi N, Taniguchi M, Kamiyama T, Furukawa H, Matsuno Y, et al: Luminal membrane expression of mesothelin is a prominent poor prognostic factor for gastric cancer. Br J Cancer. 107:137–142. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Inaguma S, Wang Z, Lasota J, Onda M, Czapiewski P, Langfort R, Rys J, Szpor J, Waloszczyk P, Okoń K, et al: Comprehensive immunohistochemical study of mesothelin (MSLN) using different monoclonal antibodies 5B2 and MN-1 in 1562 tumors with evaluation of its prognostic value in malignant pleural mesothelioma. Oncotarget. 8:26744–26754. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Li YR, Xian RR, Ziober A, Conejo-Garcia J, Perales-Puchalt A, June CH, Zhang PJ and Tchou J: Mesothelin expression is associated with poor outcomes in breast cancer. Breast Cancer Res Treat. 147:675–684. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Thomas A, Chen Y, Berman A, Schrump DS, Giaccone G, Pastan I, Venzon DJ, Liewehr DJ, Steinberg SM, Miettinen M, et al: Expression of mesothelin in thymic carcinoma and its potential therapeutic significance. Lung Cancer. 101:104–110. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Yen MJ, Hsu CY, Mao TL, Wu TC, Roden R, Wang TL and Shih IeM: Diffuse mesothelin expression correlates with prolonged patient survival in ovarian serous carcinoma. Clin Cancer Res. 12:827–831. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Kawamata F, Homma S, Kamachi H, Einama T, Kato Y, Tsuda M, Tanaka S, Maeda M, Kajino K, Hino O, et al: C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma. J Gastroenterol. 49:81–92. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Shiraishi T, Shinto E, Mochizuki S, Tsuda H, Kajiwara Y, Okamoto K, Einama T, Hase K and Ueno H: Mesothelin expression has prognostic value in stage II/III colorectal cancer. Virchows Arch. 474:297–307. 2019. View Article : Google Scholar : PubMed/NCBI

17 

Kim H, Chung Y, Paik SS, Jang K and Shin SJ: Mesothelin expression and its prognostic role according to microsatellite instability status in colorectal adenocarcinoma. Medicine (Baltimore). 98:e162072019. View Article : Google Scholar : PubMed/NCBI

18 

Lv J and Li P: Mesothelin as a biomarker for targeted therapy. Biomark Res. 7:182019. View Article : Google Scholar : PubMed/NCBI

19 

Kanda Y: Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 48:452–458. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Inaguma S, Lasota J, Felisiak-Golabek A, Kowalik A, Wang Z, Zieba S, Kalisz J, Ikeda H and Miettinen M: Histopathological and genotypic characterization of metastatic colorectal carcinoma with PD-L1 (CD274)-expression: Possible roles of tumour micro environmental factors for CD274 expression. J Pathol Clin Res. 3:268–278. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Inaguma S, Ito H, Riku M, Ikeda H and Kasai K: Addiction of pancreatic cancer cells to zinc-finger transcription factor ZIC2. Oncotarget. 6:28257–28268. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Inaguma S, Kasai K and Ikeda H: GLI1 facilitates the migration and invasion of pancreatic cancer cells through MUC5AC-mediated attenuation of E-cadherin. Oncogene. 30:714–723. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Inaguma S, Riku M, Hashimoto M, Murakami H, Saga S, Ikeda H and Kasai K: GLI1 interferes with the DNA mismatch repair system in pancreatic cancer through BHLHE41-mediated suppression of MLH1. Cancer Res. 73:7313–7323. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Onda M, Willingham M, Nagata S, Bera TK, Beers R, Ho M, Hassan R, Kreitman RJ and Pastan I: New monoclonal antibodies to mesothelin useful for immunohistochemistry, fluorescence-activated cell sorting, Western blotting, and ELISA. Clin Cancer Res. 11:5840–5846. 2005. View Article : Google Scholar : PubMed/NCBI

25 

Hmeljak J, Sanchez-Vega F, Hoadley KA, Shih J, Stewart C, Heiman D, Tarpey P, Danilova L, Drill E, Gibb EA, et al: Integrative molecular characterization of malignant pleural mesothelioma. Cancer Discov. 8:1548–1565. 2018. View Article : Google Scholar : PubMed/NCBI

26 

Bharadwaj U, Marin-Muller C, Li M, Chen C and Yao Q: Mesothelin overexpression promotes autocrine IL-6/sIL-6R trans-signaling to stimulate pancreatic cancer cell proliferation. Carcinogenesis. 32:1013–1024. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Chang MC, Chen CA, Hsieh CY, Lee CN, Su YN, Hu YH and Cheng WF: Mesothelin inhibits paclitaxel-induced apoptosis through the PI3K pathway. Biochem J. 424:449–458. 2009. View Article : Google Scholar : PubMed/NCBI

28 

Servais EL, Colovos C, Rodriguez L, Bograd AJ, Nitadori J, Sima C, Rusch VW, Sadelain M and Adusumilli PS: Mesothelin overexpression promotes mesothelioma cell invasion and MMP-9 secretion in an orthotopic mouse model and in epithelioid pleural mesothelioma patients. Clin Cancer Res. 18:2478–2489. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Masugi Y, Nishihara R, Hamada T, Song M, da Silva A, Kosumi K, Gu M, Shi Y, Li W, Liu L, et al: Tumor PDCD1LG2 (PD-L2) Expression and the lymphocytic reaction to colorectal cancer. Cancer Immunol Res. 5:1046–1055. 2017. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Inoue S, Tsunoda T, Riku M, Ito H, Inoko A, Murakami H, Ebi M, Ogasawara N, Pastan I, Kasugai K, Kasugai K, et al: Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer. Oncol Lett 19: 1741-1750, 2020.
APA
Inoue, S., Tsunoda, T., Riku, M., Ito, H., Inoko, A., Murakami, H. ... Inaguma, S. (2020). Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer. Oncology Letters, 19, 1741-1750. https://doi.org/10.3892/ol.2020.11290
MLA
Inoue, S., Tsunoda, T., Riku, M., Ito, H., Inoko, A., Murakami, H., Ebi, M., Ogasawara, N., Pastan, I., Kasugai, K., Kasai, K., Ikeda, H., Inaguma, S."Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer". Oncology Letters 19.3 (2020): 1741-1750.
Chicago
Inoue, S., Tsunoda, T., Riku, M., Ito, H., Inoko, A., Murakami, H., Ebi, M., Ogasawara, N., Pastan, I., Kasugai, K., Kasai, K., Ikeda, H., Inaguma, S."Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer". Oncology Letters 19, no. 3 (2020): 1741-1750. https://doi.org/10.3892/ol.2020.11290
Copy and paste a formatted citation
x
Spandidos Publications style
Inoue S, Tsunoda T, Riku M, Ito H, Inoko A, Murakami H, Ebi M, Ogasawara N, Pastan I, Kasugai K, Kasugai K, et al: Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer. Oncol Lett 19: 1741-1750, 2020.
APA
Inoue, S., Tsunoda, T., Riku, M., Ito, H., Inoko, A., Murakami, H. ... Inaguma, S. (2020). Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer. Oncology Letters, 19, 1741-1750. https://doi.org/10.3892/ol.2020.11290
MLA
Inoue, S., Tsunoda, T., Riku, M., Ito, H., Inoko, A., Murakami, H., Ebi, M., Ogasawara, N., Pastan, I., Kasugai, K., Kasai, K., Ikeda, H., Inaguma, S."Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer". Oncology Letters 19.3 (2020): 1741-1750.
Chicago
Inoue, S., Tsunoda, T., Riku, M., Ito, H., Inoko, A., Murakami, H., Ebi, M., Ogasawara, N., Pastan, I., Kasugai, K., Kasai, K., Ikeda, H., Inaguma, S."Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer". Oncology Letters 19, no. 3 (2020): 1741-1750. https://doi.org/10.3892/ol.2020.11290
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