GEFT protein expression in digestive tract malignant tumors and its clinical significance

被引:6
作者
Wang, Yuanyuan [1 ]
Zhang, Bing [1 ]
Gao, Ge [1 ]
Zhang, Yinping [1 ]
Xia, Qingxin [1 ]
机构
[1] Zhengzhou Univ, Henan Canc Hosp, Dept Pathol, Affiliated Canc Hosp, 127 Dongming Rd, Zhengzhou 450008, Henan, Peoples R China
关键词
guanine nucleotide exchange factor T; human epidermal growth factor receptor-2; microsatellite instability; KRAS; digestive tract malignant tumor; esophageal squamous carcinoma; gastric carcinoma and colorectal cancer; NUCLEOTIDE-EXCHANGE-FACTOR; GASTRIC-CANCER PATIENTS; MICROSATELLITE INSTABILITY; HER2; EXPRESSION; PROGNOSTIC-SIGNIFICANCE; LAUREN CLASSIFICATION; COLORECTAL-CANCER; POOR-PROGNOSIS; RAS MUTATIONS; COLON-CANCER;
D O I
10.3892/ol.2019.10915
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Guanine nucleotide exchange factor T (GEFT), a member of the Rho guanine nucleotide exchange factor family, is expressed in a variety of tumors. In the present study, the expression and clinical significance of GEFT in malignant digestive tract tumors was assessed. Tumor and adjacent control samples from 180 patients were tested. Positive GEFT expression rates were 80, 83.33 and 86.67% in esophageal squamous carcinoma (ESCC), gastric carcinoma (GC) and colorectal cancer (CRC), respectively. GEFT expression was associated with diffuse type carcinoma according to the Lauren classification (chi(2)=12.525, P=0.002) and tumor-node-metastasis (TNM) stages III/IV (chi(2)=4.033, P=0.045) in GC, and with vessel carcinoma embolus (chi(2)=7.890, P=0.005) and lymph node metastasis (chi(2)=5.455, P=0.020) in CRC, but was not associated with other clinicopathological parameters. Patients with high levels of GEFT protein expression had a less favorable outcome compared with patients with low levels of GEFT expression in patients with CRC (chi(2)=3.876, P=0.049). However, a significant association was not found between GEFT expression and overall survival in patients with ESCC (chi(2)=0.040, P=0.842) or GC (chi(2)=0.501, P=0.479). The rate of human epidermal growth factor receptor 2 upregulation in patients with GC was 13.33% and it was associated with nerve invasion (chi(2)=4.005, P=0.045) and TNM stages III/IV (chi(2)=5.600, P=0.018). Mismatch repair protein (MMRP) defect was observed in six cases, and the KRAS mutation rate was 26.67% in patients with CRC. GEFT expression was significantly correlated with MMRP (r=-0.285, P=0.027) and KRAS mutation in patients with CRC (r=0.697, P<0.001). These findings revealed frequent GEFT upregulation in malignant digestive tract tumors, which may have promoted tumor development. GEFT expression in CRC may be associated with microsatellite instability and KRAS mutation status, suggesting that GEFT may be a potential therapeutic target for patients with CRC.
引用
收藏
页码:5577 / 5590
页数:14
相关论文
共 57 条
[31]   The clinicopathological parameters and prognostic significance of HER2 expression in gastric cancer patients: a meta-analysis of literature [J].
Lei, Yu-ying ;
Huang, Jin-yu ;
Zhao, Qiong-rui ;
Jiang, Nan ;
Xu, Hui-mian ;
Wang, Zhen-ning ;
Li, Hai-qing ;
Zhang, Shi-bo ;
Sun, Zhe .
WORLD JOURNAL OF SURGICAL ONCOLOGY, 2017, 15
[32]   Clinicopathological and prognostic significance of HER2 overexpression in gastric cancer: a meta-analysis of the literature [J].
Liang, Ji-wang ;
Zhang, Jian-jun ;
Zhang, Tao ;
Zheng, Zhi-chao .
TUMOR BIOLOGY, 2014, 35 (05) :4849-4858
[33]   KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer [J].
Lièvre, A ;
Bachet, JB ;
Le Corre, D ;
Boige, V ;
Landi, B ;
Emile, JF ;
Côté, JF ;
Tomasic, G ;
Penna, C ;
Ducreux, M ;
Rougier, P ;
Penault-Llorca, F ;
Laurent-Puig, P .
CANCER RESEARCH, 2006, 66 (08) :3992-3995
[34]  
Liu CX, 2014, INT J CLIN EXP PATHO, V7, P690
[35]   p63RhoGEF and GEFT are Rho-specific guanine nucleotide exchange factors encoded by the same gene [J].
Lutz, S ;
Freichel-Blomquist, A ;
Rümenapp, U ;
Schmidt, M ;
Jakobs, KH ;
Wieland, T .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2004, 369 (05) :540-546
[36]  
Moore MA, 2010, ASIAN PAC J CANCER P, V11, P17
[37]   High-Resolution Array CGH Identifies Common Mechanisms that Drive Embryonal Rhabdomyosarcoma Pathogenesis [J].
Paulson, Vera ;
Chandler, Garvin ;
Rakheja, Dinesh ;
Galindo, Rene L. ;
Wilson, Kathleen ;
Amatruda, James F. ;
Cameron, Scott .
GENES CHROMOSOMES & CANCER, 2011, 50 (06) :397-408
[38]   Randomized Phase III Study of Panitumumab With Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) Compared With FOLFIRI Alone As Second-Line Treatment in Patients With Metastatic Colorectal Cancer [J].
Peeters, Marc ;
Price, Timothy Jay ;
Cervantes, Andres ;
Sobrero, Alberto F. ;
Ducreux, Michel ;
Hotko, Yevhen ;
Andre, Thierry ;
Chan, Emily ;
Lordick, Florian ;
Punt, Cornelis J. A. ;
Strickland, Andrew H. ;
Wilson, Gregory ;
Ciuleanu, Tudor-Eliade ;
Roman, Laslo ;
Van Cutsem, Eric ;
Tzekova, Valentina ;
Collins, Simon ;
Oliner, Kelly S. ;
Rong, Alan ;
Gansert, Jennifer .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (31) :4706-4713
[39]  
PELTOMAKI P, 1993, CANCER RES, V53, P5853
[40]   Oesophageal carcinoma [J].
Pennathur, Arjun ;
Gibson, Michael K. ;
Jobe, Blair A. ;
Luketich, James D. .
LANCET, 2013, 381 (9864) :400-412