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Article

The close association between IL‑12Rβ2 and p38MAPK, and higher expression in the early stages of NSCLC, indicates a good prognosis for survival

  • Authors:
    • Zhaoguo Liu
    • Weilin Yang
    • Shibin Yang
    • Kaican Cai
  • View Affiliations / Copyright

    Affiliations: Department of General Thoracic Surgery, First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510089, P.R. China, Department of Gastrointestinal Surgery, First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510089, P.R. China, Department of Cardio‑Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510089, P.R. China
  • Pages: 2307-2313
    |
    Published online on: June 22, 2018
       https://doi.org/10.3892/mmr.2018.9206
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Abstract

Interleukin‑12 receptor (IL‑12R) and p38 mitogen‑activated protein kinase (p38MAPK) serve an important role in non‑small cell lung cancer (NSCLC). It has previously been suggested that IL‑12Rβ2 may be involved in key regulatory pathways and interacts with the p38MAPK signaling pathway. The present study aimed to elucidate the possible association and roles of IL‑12Rβ2 and p38MAPK in NSCLC. The protein expression levels of IL‑12Rβ2 and p38MAPK were measured in 230 NSCLC tissue samples by immunohistochemistry (IHC) and western blot analyses. In addition, an immunofluorescence assay was used to observe the expression levels of these proteins in A549 and H358 cells. The associations between IL‑12Rβ2, p38MAPK and clinical characteristics, were evaluated by Pearson χ2 and Spearman correlation tests. Kaplan‑Meier plots (log‑rank test) and Cox proportional hazard models were used to analyze overall survival (OS). Compared with in benign pulmonary tissues, the expression levels of IL‑12Rβ2 and p38MAPK were not demonstrated to be significantly different in I+II pathological tumor‑node‑metastasis (pTNM) stage NSCLC tissues; however, reduced expression was detected in III+IV pTNM stage NSCLC tissues. Analysis of the association between advanced stage pTNM and the expression of both proteins demonstrated a significantly decreased Allred score (both P<0.0001), which was confirmed by IHC and western blot analyses. The IHC results demonstrated a significant correlation between IL‑12Rβ2 and p38MAPK expression (r=0.415, P=0.0143). By analyzing IL‑12Rβ2, p38MAPK expression and clinical characteristics, it was identified that IL‑12Rβ2 was significantly associated with gender (P=0.0168), age (P=0.0341), histological type (P<0.0001) and pTNM stage (P<0.0001). p38MAPK demonstrated a strong association with gender (P=0.0082) and pTNM stage (P<0.0001). The results of a Kaplan‑Meier analysis indicated that positive IL‑12Rβ2 and p38MAPK expression was associated with increased OS compared with negative protein expression. The Cox proportional hazard models revealed that IL‑12Rβ2 and p38MAPK predicted a long OS. To the best of our knowledge, the present study is the first to reveal a close association between IL‑12Rβ2 and p38MAPK, and their possible function in NSCLC progression. It further demonstrated that expression of both proteins was lower with advanced pTNM staging, whereas a high expression of both proteins was associated with improved prognosis in NSCLC.
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1 

Kamangar F, Dores GM and Anderson WF: Patterns of cancer incidence, mortality, and prevalence across five continents: Defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 24:2137–2150. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Suzuki M, Iizasa T, Nakajima T, Kubo R, Iyoda A, Hiroshima K, Nakatani Y and Fujisawa T: Aberrant methylation of IL-12Rβ2 gene in lung cancer. J Thorac oncol. 2 8 Suppl 4:S4932007. View Article : Google Scholar

3 

Orlova A, Hofström C, Strand J, Varasteh Z, Sandstrom M, Andersson K, Tolmachev V and Gräslund T: [99mTc(CO)3]+-(HE)3-ZIGF1R:4551, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours. Eur J Nucl Med Mol Imaging. 40:439–449. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Nose N, Uramoto H, Iwata T, Hanagiri T and Yasumoto K: Expression of estrogen receptor beta predicts a clinical response and longer progression-free survival after treatment with EGFR-TKI for adenocarcinoma of the lung. Lung Cancer. 71:350–355. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Torres-Arzayus MI, Zhao J, Bronson R and Brown M: Estrogen-dependent and estrogen-independent mechanisms contribute to AIB1-mediated tumor formation. Cancer Res. 70:4102–4111. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Airoldi I, Cocco C, Di Carlo E, Disarò S, Ognio E, Basso G and Pistoia V: Methylation of the IL-12Rbeta2 gene as novel tumor escape mechanism for pediatric B-acute lymphoblastic leukemia cells. Cancer Res. 66:3978–3980. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Airoldi I, Di Carlo E, Banelli B, Moserle L, Cocco C, Pezzolo A, Sorrentino C, Rossi E, Romani M, Amadori A and Pistoia V: The IL-12Rbeta2 gene functions as a tumor suppressor in human B cell malignancies. J Clin Invest. 113:1651–1659. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Airoldi I, Di Carlo E, Cocco C, Caci E, Cilli M, Sorrentino C, Sozzi G, Ferrini S, Rosini S, Bertolini G, et al: IL-12 can target human lung adenocarcinoma cells and normal bronchial epithelial cells surrounding tumor lesions. PLoS One. 4:e61192009. View Article : Google Scholar : PubMed/NCBI

9 

Suzuki M, Iizasa T, Nakajima T, Kubo R, Iyoda A, Hiroshima K, Nakatani Y and Fujisawa T: Aberrant methylation of IL-12Rbeta2 gene in lung adenocarcinoma cells is associated with unfavorable prognosis. Ann Surg Oncol. 14:2636–2642. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Li H, Cao MY, Lee Y, Lee V, Feng N, Benatar T, Jin H, Wang M, Der S, Wright JA and Young AH: Virulizin, a novel immunotherapy agent, activates NK cells through induction of IL-12 expression in macrophages. Cancer Immunol Immunother. 54:1115–1126. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Lecocq M, Detry B, Guisset A and Pilette C: FcαRI-mediated inhibition of IL-12 production and priming by IFN-γ of human monocytes and dendritic cells. J Immunol. 190:2362–2371. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Kontoyiannis D, Kotlyarov A, Carballo E, Alexopoulou L, Blackshear PJ, Gaestel M, Davis R, Flavell R and Kollias G: Interleukin-10 targets p38 MAPK to modulate ARE-dependent TNF mRNA translation and limit intestinal pathology. EMBO J. 20:3760–3770. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Fahmi A, Smart N, Punn A, Jabr R, Marber M and Heads R: p42/p44-MAPK and PI3K are sufficient for IL-6 family cytokines/gp130 to signal to hypertrophy and survival in cardiomyocytes in the absence of JAK/STAT activation. Cell Signal. 25:898–909. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Korhonen R, Huotari N, Hömmö T, Leppänen T and Moilanen E: The expression of interleukin-12 is increased by MAP kinase phosphatase-1 through a mechanism related to interferon regulatory factor 1. Mol Immunol. 51:219–226. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Cuenda A and Rousseau S: p38 MAP-kinases pathway regulation, function and role in human diseases. Biochim Biophys Acta. 1773:1358–1375. 2007. View Article : Google Scholar : PubMed/NCBI

16 

He J, Liu Z, Zheng Y, Qian J, Li H, Lu Y, Xu J, Hong B, Zhang M, Lin P, et al: p38 MAPK in myeloma cells regulates osteoclast and osteoblast activity and induces bone destruction. Cancer Res. 72:6393–6402. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Tanaka Y, Gavrielides MV, Mitsuuchi Y, Fujii T and Kazanietz MG: Protein kinase C promotes apoptosis in LNCaP prostate cancer cells through activation of p38 MAPK and inhibition of the Akt survival pathway. J Biol Chem. 278:33753–33762. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Slawinska-Brych A, Zdzisinska B, Mizerska-Dudka M and Kandefer-Szerszen M: Induction of apoptosis in multiple myeloma cells by a statin-thalidomide combination can be enhanced by p38 MAPK inhibition. Leuk Res. 37:586–594. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Shen KH, Hung SH, Yin LT, Huang CS, Chao CH, Liu CL and Shih YW: Acacetin, a flavonoid, inhibits the invasion and migration of human prostate cancer DU145 cells via inactivation of the p38 MAPK signaling pathway. Mol Cell Biochem. 333:279–291. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Koul HK, Pal M and Koul S: Role of p38 MAP kinase signal transduction in solid tumors. Genes Cancer. 4:342–359. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Pietras RJ, Marquez DC, Chen HW, Tsai E, Weinberg O and Fishbein M: Estrogen and growth factor receptor interactions in human breast and non-small cell lung cancer cells. Steroids. 70:372–381. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Kawasaki H, Altieri DC, Lu CD, Toyoda M, Tenjo T and Tanigawa N: Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res. 58:5071–5074. 1998.PubMed/NCBI

23 

Shaaban AM, Green AR, Karthik S, Alizadeh Y, Hughes TA, Harkins L, Ellis IO, Robertson JF, Paish EC, Saunders PT, et al: Nuclear and cytoplasmic expression of ERbeta1, ERbeta2, and ERbeta5 identifies distinct prognostic outcome for breast cancer patients. Clin Cancer Res. 14:5228–5235. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Chi A, Chen X, Chirala M and Younes M: Differential expression of estrogen receptor beta isoforms in human breast cancer tissue. Anticancer Res. 23:211–216. 2003.PubMed/NCBI

25 

Liu ZG, Jiao XY, Chen ZG, Feng K and Luo HH: Estrogen receptorβ2 regulates interlukin-12 receptorβ2 expression via p38 mitogen-activated protein kinase signaling and inhibits non-small-cell lung cancer proliferation and invasion. Mol Med Rep. 12:248–254. 2015. View Article : Google Scholar : PubMed/NCBI

26 

Kondadasula SV, Roda JM, Parihar R, Yu J, Lehman A, Caligiuri MA, Tridandapani S, Burry RW and Carson WE III: Colocalization of the IL-12 receptor and FcgammaRIIIa to natural killer cell lipid rafts leads to activation of ERK and enhanced production of interferon-gamma. Blood. 111:4173–4183. 2008. View Article : Google Scholar : PubMed/NCBI

27 

Jana M, Dasgupta S, Pal U and Pahan K: IL-12 p40 homodimer, the so-called biologically inactive molecule, induces nitric oxide synthase in microglia via IL-12R beta 1. Glia. 57:1553–1565. 2009. View Article : Google Scholar : PubMed/NCBI

28 

Pan SH, Chao YC, Hung PF, Chen HY, Yang SC, Chang YL, Wu CT, Chang CC, Wang WL, Chan WK, et al: The ability of LCRMP-1 to promote cancer invasion by enhancing filopodia formation is antagonized by CRMP-1. J Clin Invest. 121:3189–3205. 2011. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liu Z, Yang W, Yang S and Cai K: The close association between IL‑12Rβ2 and p38MAPK, and higher expression in the early stages of NSCLC, indicates a good prognosis for survival. Mol Med Rep 18: 2307-2313, 2018.
APA
Liu, Z., Yang, W., Yang, S., & Cai, K. (2018). The close association between IL‑12Rβ2 and p38MAPK, and higher expression in the early stages of NSCLC, indicates a good prognosis for survival. Molecular Medicine Reports, 18, 2307-2313. https://doi.org/10.3892/mmr.2018.9206
MLA
Liu, Z., Yang, W., Yang, S., Cai, K."The close association between IL‑12Rβ2 and p38MAPK, and higher expression in the early stages of NSCLC, indicates a good prognosis for survival". Molecular Medicine Reports 18.2 (2018): 2307-2313.
Chicago
Liu, Z., Yang, W., Yang, S., Cai, K."The close association between IL‑12Rβ2 and p38MAPK, and higher expression in the early stages of NSCLC, indicates a good prognosis for survival". Molecular Medicine Reports 18, no. 2 (2018): 2307-2313. https://doi.org/10.3892/mmr.2018.9206
Copy and paste a formatted citation
x
Spandidos Publications style
Liu Z, Yang W, Yang S and Cai K: The close association between IL‑12Rβ2 and p38MAPK, and higher expression in the early stages of NSCLC, indicates a good prognosis for survival. Mol Med Rep 18: 2307-2313, 2018.
APA
Liu, Z., Yang, W., Yang, S., & Cai, K. (2018). The close association between IL‑12Rβ2 and p38MAPK, and higher expression in the early stages of NSCLC, indicates a good prognosis for survival. Molecular Medicine Reports, 18, 2307-2313. https://doi.org/10.3892/mmr.2018.9206
MLA
Liu, Z., Yang, W., Yang, S., Cai, K."The close association between IL‑12Rβ2 and p38MAPK, and higher expression in the early stages of NSCLC, indicates a good prognosis for survival". Molecular Medicine Reports 18.2 (2018): 2307-2313.
Chicago
Liu, Z., Yang, W., Yang, S., Cai, K."The close association between IL‑12Rβ2 and p38MAPK, and higher expression in the early stages of NSCLC, indicates a good prognosis for survival". Molecular Medicine Reports 18, no. 2 (2018): 2307-2313. https://doi.org/10.3892/mmr.2018.9206
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