Correlation of EGFR Del 19 with Fn14/JAK/STAT signaling molecules in non-small cell lung cancer

被引:26
作者
Sun, Ying [1 ]
Han, Yong [1 ]
Wang, Xiaoping [1 ]
Wang, Wuping [1 ]
Wang, Xuejiao [1 ]
Wen, Miaomiao [1 ]
Xia, Jinghua [1 ]
Xing, Hao [1 ]
Li, Xiaofei [1 ]
Zhang, Zhipei [1 ]
机构
[1] Fourth Mil Med Univ, Tangdu Hosp, Dept Thorac Surg, 1 Xinsi Rd, Xian 710038, Shaanxi, Peoples R China
关键词
non-small cell lung cancer; EGFR exon 19 deletion; Fn14; JAK1; STAT1; ENDOTHELIAL-CELLS; INDUCED APOPTOSIS; RECEPTOR FN14; TWEAK; EXPRESSION; PROMOTES; OVEREXPRESSION; PROLIFERATION; MUTATIONS; MIGRATION;
D O I
10.3892/or.2016.4905
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Previous research has shown that p-EGFR (particularly mutated EGFR) may activate fibroblast growth factor-inducible 14 (Fn14) expression in non-small cell lung cancer (NSCLC), and the JAK/STAT signaling pathway may participate in this process. Thus, in order to verify this hypothesis, correlations among the expression levels of EGFR Del 19, Fn14 and JAK/STAT were detected and analyzed. The expression and location of these molecules were assessed using IHC, immunohistofluorescence, RT-qPCR and western blotting. The differences and correlations in the expression of these molecules and clinical pathological characteristics were statistically analyzed using Mann-Whitney U, Kruskal-Wallis H and cross-table tests. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of EGFR Del 19 and Fn14 expression on survival. Data showed that EGFR Del 19, Fn14 and JAK1/STAT1 expression was significantly related with differentiation, pTNM stage and lymphatic metastasis (P<0.01) and there was a marked correlation of EGFR Del 19, Fn14 and JAK1/STAT1 expression with histological type, differentiation, pTNM stage of NSCLC (P<0.05; r(s)>0.3). Immunohistofluorescence showed that there was a co-localization phenomenon between EGFR Del 19 and Fn14 expression. NSCLC patients with higher EGFR Del 19/Fn14 expression had a significantly worse prognosis than those with lower EGFR Del 19/Fn14 expression (P=0.0155/P=0.001; log-rank test). The multivariate analysis indicated that Fn14 expression may be an independent prognostic factor in NSCLC with EGFR Del 19 [hazard ratio (HR), 0.326; P=0.042]. Therefore, our results indicate that EGFR Del 19 may promote Fn14 and JAK1/STAT1 expression in NSCLC and Fn14 may serve as a prognostic biomarker in NSCLC with EGFR Del 19.
引用
收藏
页码:1030 / 1040
页数:11
相关论文
共 29 条
  • [1] IKKβ/2 induces TWEAK and apoptosis in mammary epithelial cells
    Baxter, Fiona O.
    Came, Paul J.
    Abell, Kathrine
    Kedjouar, Blandine
    Huth, Marion
    Rajewsky, Klaus
    Pasparakis, Manolis
    Watson, Christine J.
    [J]. DEVELOPMENT, 2006, 133 (17): : 3485 - 3494
  • [2] TWEAK/Fn14 pathway: an immunological switch for shaping tissue responses
    Burkly, Linda C.
    Michaelson, Jennifer S.
    Zheng, Timothy S.
    [J]. IMMUNOLOGICAL REVIEWS, 2011, 244 : 99 - 114
  • [3] TWEAK signals through JAK-STAT to induce tumor cell apoptosis
    Chapman, Mark S.
    Wu, Lan
    Amatucci, Aldo
    Ho, Steffan N.
    Michaelson, Jennifer S.
    [J]. CYTOKINE, 2013, 61 (01) : 210 - 217
  • [4] Proinflammatory activity of TWEAK on human dermal fibroblasts and synoviocytes: blocking and enhancing effects of anti-TWEAK monoclonal antibodies
    Chicheportiche, Y
    Chicheportiche, R
    Sizing, I
    Thompson, J
    Benjamin, CB
    Ambrose, C
    Dayer, JM
    [J]. ARTHRITIS RESEARCH, 2002, 4 (02) : 126 - 133
  • [5] Activation of the STAT signaling pathway can cause expression of caspase 1 and apoptosis
    Chin, YE
    Kitagawa, M
    Kuida, K
    Flavell, RA
    Fu, XY
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (09) : 5328 - 5337
  • [6] International lung cancer trends by histologic type:: male:female differences diminishing and adenocarcinoma rates rising
    Devesa, SS
    Bray, F
    Vizcaino, AP
    Parkin, DM
    [J]. INTERNATIONAL JOURNAL OF CANCER, 2005, 117 (02) : 294 - 299
  • [7] STAT1 signaling is associated with acquired crossresistance to doxorubicin and radiation in myeloma cell lines
    Fryknas, Marten
    Dhar, Sumeer
    Oberg, Fredrik
    Rickardson, Linda
    Rydaker, Maria
    Goransson, Hanna
    Gustafsson, Mats
    Pettersson, Ulf
    Nygren, Peter
    Larsson, Rolf
    Isaksson, Anders
    [J]. INTERNATIONAL JOURNAL OF CANCER, 2007, 120 (01) : 189 - 195
  • [8] Ep-CAM overexpression in breast cancer as a predictor of survival
    Gastl, G
    Spizzo, G
    Obrist, P
    Dünser, M
    Mikuz, G
    [J]. LANCET, 2000, 356 (9246) : 1981 - 1982
  • [9] TWEAK, via its receptor Fn14, is a novel regulator of mesenchymal progenitor cells and skeletal muscle regeneration
    Girgenrath, Mahasweta
    Weng, Shawn
    Kostek, Christine A.
    Browning, Beth
    Wang, Monica
    Brown, Sharron A. N.
    Winkles, Jeffrey A.
    Michaelson, Jennifer S.
    Allaire, Norm
    Schneider, Pascal
    Scott, Martin L.
    Hsu, Yen-ming
    Yagita, Hideo
    Flavell, Richard A.
    Miller, Jeffrey Boone
    Burkly, Linda C.
    Zheng, Timothy S.
    [J]. EMBO JOURNAL, 2006, 25 (24) : 5826 - 5839
  • [10] Pro-inflammatory effect of TWEAK/Fn14 interaction on human umbilical vein endothelial cells
    Harada, N
    Nakayama, M
    Nakano, H
    Fukuchi, Y
    Yagita, H
    Okumura, K
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 299 (03) : 488 - 493