REVIEW ARTICLE
CD117 expression is correlated with poor survival of patients and progression of lung carcinoma:a meta-analysis with a panel of 2645 patients
1
Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, Zhuang Autonomous Region, People’s Republic of China
2
Department of Oncology, Sun Yat-sen University, Xiaoguwei Island, Panyu District, Guangzhou, People’s Republic of China
Submission date: 2018-06-26
Final revision date: 2019-01-14
Acceptance date: 2019-01-17
Publication date: 2019-08-28
Pol J Pathol 2019;70(2):63-78
KEYWORDS
TOPICS
ABSTRACT
The aim of this research was to investigate the clinical role and prognostic value of CD117 expression assessed immunohistochemically in lung carcinoma through a comprehensive meta-analysis in which 27 publications were acquired and 2645 patients were ultimately analysed. Statistical analysis and corresponding plots were performed using STATA version 12.0. Publication bias was assessed by Begg’s funnel plots and Egger’s test. Pooled HR and its 95% CI (HR = 1.53, 95% CI: 1.13-2.07, p = 0.007) for overall survival of patients indicated a poor prognostic value for CD117 expression in lung carcinoma, which was accompanied by heterogeneity and publication bias. In the subgroup analysis, there was strong evidence that could support an association between CD117 expression and poor prognosis in NSCLC patients (HR = 2.03, 95% CI: 1.41-2.90, p < 0.001; heterogeneity: I2 = 41.9%, c2 = 15.49, p = 0.078). Multivariate analysis also revealed consistent results in high-quality studies with reported HRs (HR = 2.16, 95% CI: 1.67-2.79, p < 0.001), and Asian patients (HR = 2.12, 95% CI: 1.45-3.10, p < 0.001). The correlations between CD117 expression and age, clinical stage, TNM stage, lymph node metastasis, or histology were not statistically significant. In conclusion, CD117 expression might be a potential marker for predicting poor prognosis, faster tumour growth, and early lymph node metastasis in NSCLC.
REFERENCES (74)
1.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018; 68: 7-30.
2.
Tan Q, Cui J, Huang J, et al. Genomic Alteration During Metastasis of Lung Adenocarcinoma. Cell Physiol Biochem 2016; 38: 469-486.
3.
Greillier L, Cortot AB, Viguier J, et al. Perception of Lung Cancer Risk: Impact of Smoking Status and Nicotine Dependence. Curr Oncol Rep2018; 20 (Suppl 1): 18.
4.
Stone E, Jett J, Warren G, et al. Cannabis Use, Lung Cancer, and Related Issues. J Thorac Oncol 2018;13: 480-487.
5.
Li TT, Gao X, Gao L, et al. Role of upregulated miR-136-5p in lung adenocarcinoma: A study of 1242 samples utilizing bioinformatics analysis. Pathol Res Pract 2018; 214: 750-766.
6.
Huang WT, Cen WL, He RQ, et al. Effect of miR146a5p on tumor growth in NSCLC using chick chorioallantoic membrane assay and bioinformatics investigation. Mol Med Rep 2017;16: 8781-8792.
7.
He RQ, Li XJ, Liang L, et al. The suppressive role of miR-542-5p in NSCLC: the evidence from clinical data and in vivo validation using a chick chorioallantoic membrane model. BMC Cancer 2017; 17: 655.
8.
Konopka KE. Diagnostic Pathology of Lung Cancer. Semin Respir Crit Care Med 2016; 37: 681-688.
9.
Liang YY, Huang JC, Tang RX, et al. Clinical value of miR-198-5p in lung squamous cell carcinoma assessed using microarray and RT-qPCR. World J Surg Oncol 2018; 16: 22.
10.
Song X, Wang Z. Clinical efficacy evaluation of tyrosine kinase inhibitors for non-adenocarcinoma lung cancer patients harboring EGFR-sensitizing mutations. Onco Targets Ther 2017; 10: 3119-3122.
11.
Gao X, Tang RX, Xie QN, et al. The clinical value of miR-193a-3p in non-small cell lung cancer and its potential molecular mechanism explored in silico using RNA-sequencing and microarray data. FEBS Open Bio 2018; 8: 94-109.
12.
Zhang Y, Chen WJ, Gan TQ, et al. Clinical Significance and Effect of lncRNA HOXA11-AS in NSCLC: A Study Based on Bioinformatics, In Vitro and in Vivo Verification. Sci Rep 2017; 7: 5567.
13.
Mengoli MC, Longo FR, Fraggetta F, et al. The 2015 World Health Organization Classification of lung tumors: new entities since the 2004 Classification. Pathologica 2018; 110: 39-67.
14.
Chen Y, Li C, Pan Y, et al. The Emerging Role and Promise of Long Noncoding RNAs in Lung Cancer Treatment. Cell Physiol Biochem 2016; 38: 2194-206.
15.
Zhao H, Chen KZ, Hui BG, et al. Role of circulating tumor DNA in the management of early-stage lung cancer. Thorac Cancer 2018; 9: 509-515.
16.
Kazaz SN, Oztop I. Immune Checkpoint Inhibitors in Advanced-Stage Non-small Cell Lung Cancer. Turk Thorac J 2017; 18: 101-107.
17.
Xu-Welliver M, Carbone DP. Blood-based biomarkers in lung cancer: prognosis and treatment decisions. Transl Lung Cancer Res 2017; 6: 708-712.
18.
Tang Y, Qiao G, Xu E, et al. Biomarkers for early diagnosis, prognosis, prediction, and recurrence monitoring of non-small cell lung cancer. Onco Targets Ther 2017; 10: 4527-4534.
19.
Wei K, Ye Z, Li Z, et al. An immunohistochemical study of cyclin-dependent kinase 5 (CDK5) expression in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC): a possible prognostic biomarker. World J Surg Oncol 2016; 14: 34.
20.
Xiao H, Wang J, Liu Y, et al. Relative influence of c-Kit expression and epidermal growth factor receptor gene amplification on survival in patients with non-small cell lung cancer. Oncol Lett 2014; 8: 582-588.
21.
Salomonsson A, Jonsson M, Isaksson S, et al. Histological specificity of alterations and expression of KIT and KITLG in non-small cell lung carcinoma. Genes Chromosomes Cancer 2013; 52: 1088-1096.
22.
Salehinejad J, Mohtasham N, Bagherpour A, et al. Evaluation of c-kit protein (CD117) expression in common salivary gland neoplasms. J Oral Maxillofac Pathol 2014; 18: 177-182.
23.
Youssef NS, Said AM. Immunohistochemical expression of CD117 and vascular endothelial growth factor in retinoblastoma: possible targets of new therapies. Int J Clin Exp Pathol 2014; 7: 5725-37.
24.
Sehitoglu I, Bedir R, Ural UM, et al. Relationships between C-kit expression and mean platelet volume in benign, preneoplastic and neoplastic endometrium. Asian Pac J Cancer Prev 2015; 16: 1495-1499.
25.
Pusztaszeri MP, Sadow PM, Faquin WC. CD117: a novel ancillary marker for papillary thyroid carcinoma in fine-needle aspiration biopsies. Cancer Cytopathol 2014; 122: 596-603.
26.
Jansson S, Bendahl PO, Grabau DA, et al. The three receptor tyrosine kinases c-KIT, VEGFR2 and PDGFRalpha, closely spaced at 4q12, show increased protein expression in triple-negative breast cancer. PLoS One 2014; 9: e102176.
27.
Xu CW, Lin S, Wang WL, et al. Analysis of mutation of the c-Kit gene and PDGFRA in gastrointestinal stromal tumors. Exp Ther Med 2015; 10: 1045-1051.
28.
Gottschling S, Jensen K, Herth FJ, et al. Lack of prognostic significance of neuroendocrine differentiation and stem cell antigen co-expression in resected early-stage non-small cell lung cancer. Anticancer Res 2013; 33: 981-990.
29.
Rehfeld N, Geddert H, Atamna A, et al. Coexpression of fragile histidine triad and c-kit is relevant for prediction of survival in patients with small cell lung cancer. Cancer Epidemiol Biomarkers Prev 2006; 15: 2232-2238.
30.
Micke P, Basrai M, Faldum A, et al. Characterization of c-kit expression in small cell lung cancer: prognostic and therapeutic implications. Clin Cancer Res 2003; 9: 188-194.
31.
Pelosi G, Barisella M, Pasini F, et al. CD117 immunoreactivity in stage I adenocarcinoma and squamous cell carcinoma of the lung: relevance to prognosis in a subset of adenocarcinoma patients. Mod Pathol 2004; 17: 711-721.
32.
Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 1998; 17: 2815-2834.
33.
Tierney JF, Stewart LA, Ghersi D, et al. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 2007; 8: 16.
34.
Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med 1997; 127: 820-826.
35.
Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-1558.
36.
Peters JL, Sutton AJ, Jones DR, et al. Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry. J Clin Epidemiol 2008; 61: 991-996.
37.
Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-634.
38.
Moreno SG, Sutton AJ, Ades AE, et al. Assessment of regression-based methods to adjust for publication bias through a comprehensive simulation study. BMC Med Res Methodol 2009; 9: 2.
39.
Pelosi G, Masullo M, Leon ME, et al. CD117 immunoreactivity in high-grade neuroendocrine tumors of the lung: a comparative study of 39 large-cell neuroendocrine carcinomas and 27 surgically resected small-cell carcinomas. Virchows Arch 2004; 445: 449-455.
40.
Araki K, Ishii G, Yokose T, et al. Frequent overexpression of the c-kit protein in large cell neuroendocrine carcinoma of the lung. Lung Cancer 2003; 40: 173-180.
41.
Boldrini L, Ursino S, Gisfredi S, et al. Expression and mutational status of c-kit in small-cell lung cancer: prognostic relevance. Clin Cancer Res 2004; 10: 4101-4108.
42.
Rohr UP, Rehfeld N, Pflugfelder L, et al. Expression of the tyrosine kinase c-kit is an independent prognostic factor in patients with small cell lung cancer. Int J Cancer 2004; 111: 259-263.
43.
Yoo J, Kim CH, Song SH, et al. Expression of c-kit and p53 in non-small cell lung cancers. Cancer Res Treat 2004; 36:167-172.
44.
Leina S. Expression of c-Kit Protein in Small Cell Lung Cancer and Its Prognostic Implications. Tianjin Medical University; 2005.
45.
Na D, Leina S, Zhongli Z, et al. Expression of c-KIT, PDGFR-α and PDGFR-β protein in neuroendocrine lung cancer tissues and its clinical significance. Shandong Med J 2010; 2010: 4-6.
46.
Po Z, Ning H, Yun S, et al. Clinicopathological significance of expression of c-kit protein in neuroendocrine lung carcinoma. Nat Med J China 2005; 2005: 1526-1529.
47.
Casali C, Stefani A, Rossi G, et al. The prognostic role of c-kit protein expression in resected large cell neuroendocrine carcinoma of the lung. Ann Thorac Surg 2004; 77: 247-252.
48.
Blackhall FH, Pintilie M, Michael M, et al. Expression and prognostic significance of kit, protein kinase B, and mitogen-activated protein kinase in patients with small cell lung cancer. Clin Cancer Res 2003; 9: 2241-2247.
49.
Micke P, Hengstler JG, Albrecht H, et al. c-kit expression in adenocarcinomas of the lung. Tumour Biol 2004; 25: 235-242.
50.
Jiang X, Zhao P. Expression of c-kit protein and its significance in human small cell lung cancer. Chin J Lung Cancer 2004; 7: 206-208.
51.
Potti A, Moazzam N, Ramar K, et al. CD117 (c-KIT) overexpression in patients with extensive-stage small-cell lung carcinoma. Ann Oncol 2003; 14: 894-897.
52.
Zhao F, Chen Y, Wu Q, et al. Prognostic value of CD117 in cancer: a meta-analysis. Int J Clin Exp Pathol 2014; 7: 1012-1021.
53.
Yan L, Zou L, Zhao W, et al. Clinicopathological significance of c-KIT mutation in gastrointestinal stromal tumors: a systematic review and meta-analysis. Sci Rep 2015; 5: 13718.
54.
Rossi G, Cavazza A, Marchioni A, et al. Kit expression in small cell carcinomas of the lung: effects of chemotherapy. Mod Pathol 2003; 16: 1041-1047.
55.
Gillinov M, Moskowitz AJ, Argenziano M. Surgical Ablation for Atrial Fibrillation. N Engl J Med 2015; 373: 484.
56.
Conic I, Stanojevic Z, Jankovic Velickovic L, et al. Epithelial ovarian cancer with CD117 phenotype is highly aggressive and resistant to chemotherapy. J Obstet Gynaecol Res 2015; 41: 1630-1637.
57.
Ma YY, Yu S, He XJ, et al. Involvement of c-KIT mutation in the development of gastrointestinal stromal tumors through proliferation promotion and apoptosis inhibition. Onco Targets Ther 2014; 7: 637-643.
58.
Xu C, Han H, Wang J, et al. Diagnosis value of CD117 and PDGFRA, alone or in combination DOG1, as biomarkers for gastrointestinal stromal tumors. Ann Transl Med 2015; 3: 308.
59.
Xu CW, Lin S, Wang WL, et al. Analysis of mutation of the c-Kit gene and in gastrointestinal stromal tumors. Exp Ther Med 2015; 10: 1045-1051.
60.
Mikami T, Nemoto Y, Numata Y, et al. Small gastrointestinal stromal tumor in the stomach: identification of precursor for clinical gastrointestinal stromal tumor using c-kit and alpha-smooth muscle actin expression. Hum Pathol 2013; 44: 2628-2635.
61.
Novelli M, Rossi S, Rodriguez-Justo M, et al. DOG1 and CD117 are the antibodies of choice in the diagnosis of gastrointestinal stromal tumours. Histopathology 2010; 57: 259-270.
62.
Nakahara M, Isozaki K, Hirota S, et al. A novel gain-of-function mutation of c-kit gene in gastrointestinal stromal tumors. Gastroenterology 1998; 115: 1090-1095.
63.
Camps C, Sirera R, Bremnes RM, et al. Analysis of c-kit expression in small cell lung cancer: prevalence and prognostic implications. Lung Cancer 2006; 52: 343-347.
64.
Gao J, Tian Y, Li J, et al. Secondary mutations of c-KIT contribute to acquired resistance to imatinib and decrease efficacy of sunitinib in Chinese patients with gastrointestinal stromal tumors. Med Oncol 2013; 30: 522.
65.
Gao J, Dang Y, Sun N, et al. C-KIT mutations were closely associated with the response to Imatinib in Chinese advanced gastrointestinal stromal tumor patients. Med Oncol 2012; 29: 3039-3045.
66.
Miselli FC, Casieri P, Negri T, et al. c-Kit/PDGFRA gene status alterations possibly related to primary imatinib resistance in gastrointestinal stromal tumors. Clin Cancer Res 2007; 13: 2369-2377.
67.
Zhang L, Yang X, Zhao B, et al. Acquired resistance to EGFR tyrosine kinase inhibitor in A431 squamous cell carcinoma xenografts is mediated by c-Kit pathway transduction. Tumour Biol 2015; 36: 2993-2999.
68.
Lu HY, Zhang G, Cheng QY, et al. Expression and mutation of the c-kit gene and correlation with prognosis of small cell lung cancer. Oncol Lett 2012; 4: 89-93.
69.
Guo JH, Zhou J, Zhao Y, et al. Normal peripheral prostate stromal cells stimulate prostate cancer development: roles of c-kit signal. Am J Transl Res 2015; 7: 502-512.
70.
Tan J, Yang S, Shen P, et al. C-kit signaling promotes proliferation and invasion of colorectal mucinous adenocarcinoma in a murine model. Oncotarget 2015; 6: 27037-27048.
71.
Liu Q, Huang X, Zhang H, et al. c-kit(+) cells adopt vascular endothelial but not epithelial cell fates during lung maintenance and repair. Nat Med 2015; 21: 866-868.
72.
Krug LM, Crapanzano JP, Azzoli CG, et al. Imatinib mesylate lacks activity in small cell lung carcinoma expressing c-kit protein: a phase II clinical trial. Cancer 2005; 103: 2128-2131.
73.
Sakabe T, Azumi J, Haruki T, et al. CD117 expression is a predictive marker for poor prognosis in patients with non-small cell lung cancer. Oncol Lett 2017; 13: 3703-3708.
74.
Zhao P, Hou N, Shao Y, et al. Clinicopathological significance of expression of c-kit protein in neuroendocrine lung carcinoma. Nat Med J China 2005; 85: 1526-1529.
| eISSN: | 2084-9869 |
| ISSN: | 1233-9687 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
