An immunohistochemical analysis-based decision tree model for estimating the risk of lymphatic metastasis in pN0 squamous cell carcinomas of the lung
Yu Liu
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
These authors contributed equally to this paper.
Search for more papers by this authorDongmei Lin
Department of Pathology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
These authors contributed equally to this paper.
Search for more papers by this authorTing Xiao
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorYing Ma
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorZhi Hu
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorHongwei Zheng
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorShan Zheng
Department of Pathology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Search for more papers by this authorYan Liu
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorMin Li
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorLin Li
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorYan Cao
Department of Pathology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Search for more papers by this authorSuping Guo
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorNaijun Han
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorXuebing Di
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorKaitai Zhang
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorShujun Cheng
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorYanning Gao
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorYu Liu
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
These authors contributed equally to this paper.
Search for more papers by this authorDongmei Lin
Department of Pathology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
These authors contributed equally to this paper.
Search for more papers by this authorTing Xiao
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorYing Ma
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorZhi Hu
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorHongwei Zheng
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorShan Zheng
Department of Pathology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Search for more papers by this authorYan Liu
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorMin Li
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorLin Li
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorYan Cao
Department of Pathology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Search for more papers by this authorSuping Guo
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorNaijun Han
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorXuebing Di
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorKaitai Zhang
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorShujun Cheng
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorYanning Gao
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences
Search for more papers by this authorAbstract
Liu Y, Lin D, Xiao T, Ma Y, Hu Z, Zheng H, Zheng S, Liu Y, Li M, Li L, Cao Y, Guo S, Han N, Di X, Zhang K, Cheng S & Gao Y (2011) Histopathology 59, 882–891
An immunohistochemical analysis-based decision tree model for estimating the risk of lymphatic metastasis in pN0 squamous cell carcinomas of the lung
Aims: Lung cancer patients within the pN0 category have a significantly different outcome. The aim of this study was to develop a mathematical model to assist in predicting the prognosis of pN0 lung squamous cell carcinoma (SCC).
Methods and results: Twenty-three proteins were examined by immunohistochemical (IHC) analysis on primary tumour tissues from 319 lung SCC patients. In a training group, using IHC data, a recursive partitioning decision tree (RP-DT) was used to build a model for estimating the risk for lymphatic metastasis. This model was then validated in a test cohort. Of 23 proteins, 8 (matrix metallopeptidase 1, metalloproteinase inhibitor 1, Ras GTPase-activating-like protein IQGAP1, targeting protein for Xklp2, urokinase-type plasminogen activator, cathepsin D, fascin, polymeric immunoglobulin receptor/secretory component) were selected, and generated a tree model in a training group of 255 patients to classify them as at high or low risk of lymphatic invasion, with accuracy of 78.0% (compared to histopathological diagnosis), sensitivity of 83.0% and specificity of 70.3%. When the tree model was applied to the test group, the accuracy, sensitivity and specificity were 76.6%, 76.0% and 76.9%, respectively. The performance of this mathematical model was substantiated further in 34 ‘problematic’ stage I/pN0 patients by survival analysis.
Conclusions: The RP-DT model, constructed with eight protein markers for estimating lymphatic metastasis risk in pN0 lung SCC, is clinically feasible and practical, using IHC data from the primary tumour.
Supporting Information
Table S1. The demographic data and clinical characteristics of the patients with SCC of the lung in the training set and test set.
| Filename | Description |
|---|---|
| HIS_4013_sm_TableS1.doc39 KB | Supporting info item |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1 Jemal A, Siegel R, Ward E et al. Cancer statistics, 2008. CA Cancer J. Clin. 2008; 58; 71–96.
- 2 Herbst RS, Lippman SM. Molecular signatures of lung cancer – toward personalized therapy. N. Engl. J. Med. 2007; 356; 76–78.
- 3 Herbst RS, Heymach JV, Lippman SM. Lung cancer. N. Engl. J. Med. 2008; 359; 1367–1380.
- 4 Bhattacharjee A, Richards WG, Staunton J et al. Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc. Natl Acad. Sci. USA 2001; 98; 13790–13795.
- 5 Meyerson M, Carbone D. Genomic and proteomic profiling of lung cancers: lung cancer classification in the age of targeted therapy. J. Clin. Oncol. 2005; 23; 3219–3226.
- 6 Beer DG, Kardia SL, Huang CC et al. Gene-expression profiles predict survival of patients with lung adenocarcinoma. Nat. Med. 2002; 8; 816–824.
- 7 Chen HY, Yu SL, Chen CH et al. A five-gene signature and clinical outcome in non-small-cell lung cancer. N. Engl. J. Med. 2007; 356; 11–20.
- 8 Potti A, Mukherjee S, Petersen R et al. A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer. N. Engl. J. Med. 2006; 355; 570–580.
- 9 Shedden K, Taylor JM, Enkemann SA et al. Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study. Nat. Med. 2008; 14; 822–827.
- 10 Liu Y, Sun W, Zhang K et al. Identification of genes differentially expressed in human primary lung squamous cell carcinoma. Lung Cancer 2007; 56; 307–317.
- 11 Sun W, Zhang K, Zhang X et al. Identification of differentially expressed genes in human lung squamous cell carcinoma using suppression subtractive hybridization. Cancer Lett. 2004; 212; 83–93.
- 12 Xiao T, Ying W, Li L et al. An approach to studying lung cancer-related proteins in human blood. Mol. Cell Proteomics 2005; 4; 1480–1486.
- 13 International Union Against Cancer (UICC). Lung and pleural tumours. In LH Sobin, C Wittekind eds. TNM Classification of Malignant Tumours, 6th edn. New York: Wiley-Blackwell, 2002; 97–108.
- 14 Ma Y, Lin D, Sun W et al. Expression of targeting protein for xklp2 associated with both malignant transformation of respiratory epithelium and progression of squamous cell lung cancer. Clin. Cancer Res. 2006; 12; 1121–1127.
- 15 Vakkala M, Kahlos K, Lakari E, Paakko P, Kinnula V, Soini Y. Inducible nitric oxide synthase expression, apoptosis, and angiogenesis in in situ and invasive breast carcinomas. Clin. Cancer Res. 2000; 6; 2408–2416.
- 16 Hothorn T, Hornik K, Zeileis A. Unbiased Recursive Partitioning: A Conditional Inference Framework. Journal of Computational and Graphical Statistics 2006; 15; 651–674.
- 17
R Development Core Team.
R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing, 2008.
10.1890/0012-9658(2002)083[3097:CFHIWS]2.0.CO;2 Google Scholar
- 18 Rami-Porta R, Crowley JJ, Goldstraw P. The revised TNM staging system for lung cancer. Ann. Thorac. Cardiovasc. Surg. 2009; 15; 4–9.
- 19 Rusch VW, Crowley J, Giroux DJ et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming seventh edition of the TNM classification for lung cancer. J. Thorac. Oncol. 2007; 2; 603–612.
- 20 Yamasaki M, Takemasa I, Komori T et al. The gene expression profile represents the molecular nature of liver metastasis in colorectal cancer. Int. J. Oncol. 2007; 30; 129–138.
- 21 Ramaswamy S, Ross KN, Lander ES, Golub TR. A molecular signature of metastasis in primary solid tumors. Nat. Genet. 2003; 33; 49–54.
- 22 Ma J, Gao M, Lu Y et al. Gain of 1q25–32, 12q23–24.3, and 17q12–22 facilitates tumorigenesis and progression of human squamous cell lung cancer. J. Pathol. 2006; 210; 205–213.
- 23 Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100; 57–70.
- 24 Hu Z, Lin D, Yuan J et al. Overexpression of osteopontin is associated with more aggressive phenotypes in human non-small cell lung cancer. Clin. Cancer Res. 2005; 11; 4646–4652.
- 25 Lou X, Xiao T, Zhao K et al. Cathepsin D is secreted from M-BE cells: its potential role as a biomarker of lung cancer. J. Proteome Res. 2007; 6; 1083–1092.
- 26 Yuan J, Ma J, Zheng H et al. Overexpression of OLC1, cigarette smoke, and human lung tumorigenesis. J. Natl Cancer Inst. 2008; 100; 1592–1605.
- 27 Lu X, Wang Q, Hu G et al. ADAMTS1 and MMP1 proteolytically engage EGF-like ligands in an osteolytic signaling cascade for bone metastasis. Genes Dev. 2009; 23; 1882–1894.
- 28 Chambers AF, Matrisian LM. Changing views of the role of matrix metalloproteinases in metastasis. J. Natl Cancer Inst. 1997; 89; 1260–1270.
- 29 Schmalfeldt B, Kuhn W, Reuning U et al. Primary tumor and metastasis in ovarian cancer differ in their content of urokinase-type plasminogen activator, its receptor, and inhibitors types 1 and 2. Cancer Res. 1995; 55; 3958–3963.
- 30
van der Burg ME,
Henzen-Logmans SC,
Berns EM,
van Putten WL,
Klijn JG,
Foekens JA.
Expression of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in benign, borderline, malignant primary and metastatic ovarian tumors.
Int. J. Cancer
1996; 69; 475–479.
10.1002/(SICI)1097-0215(19961220)69:6<475::AID-IJC10>3.0.CO;2-0 CAS PubMed Web of Science® Google Scholar
- 31 Gouyer V, Conti M, Devos P et al. Tissue inhibitor of metalloproteinase 1 is an independent predictor of prognosis in patients with nonsmall cell lung carcinoma who undergo resection with curative intent. Cancer 2005; 103; 1676–1684.
- 32 Fong KM, Kida Y, Zimmerman PV, Smith PJ. TIMP1 and adverse prognosis in non-small cell lung cancer. Clin. Cancer Res. 1996; 2; 1369–1372.
- 33
Brouillet JP,
Dufour F,
Lemamy G
et al.
Increased cathepsin D level in the serum of patients with metastatic breast carcinoma detected with a specific pro-cathepsin D immunoassay.
Cancer
1997; 79; 2132–2136.
10.1002/(SICI)1097-0142(19970601)79:11<2132::AID-CNCR10>3.0.CO;2-X CAS PubMed Web of Science® Google Scholar
- 34 Oh-e H, Tanaka S, Kitadai Y, Shimamoto F, Yoshihara M, Haruma K. Cathepsin D expression as a possible predictor of lymph node metastasis in submucosal colorectal cancer. Eur. J. Cancer 2001; 37; 180–188.
- 35 Dong P, Nabeshima K, Nishimura N et al. Overexpression and diffuse expression pattern of IQGAP1 at invasion fronts are independent prognostic parameters in ovarian carcinomas. Cancer Lett. 2006; 243; 120–127.
- 36 Hwang JH, Smith CA, Salhia B, Rutka JT. The role of fascin in the migration and invasiveness of malignant glioma cells. Neoplasia 2008; 10; 149–159.
- 37 Pelosi G, Pastorino U, Pasini F et al. Independent prognostic value of fascin immunoreactivity in stage I nonsmall cell lung cancer. Br. J. Cancer 2003; 88; 537–547.
- 38 Li M, Xiao T, Zhang Y et al. Prognostic significance of matrix metalloproteinase-1 levels in peripheral plasma and tumour tissues of lung cancer patients. Lung Cancer 2010; 69; 341–347.
- 39 Xiao T, Lin D, Li M. Expression of polymeric immunoglobulin receptor (pigR/SC) in lung cancer tissues. Carcinog. Teratog. Mutagen. 2008; 20; 182–184.
- 40 Jan Y, Matter M, Pai JT et al. A mitochondrial protein, Bit1, mediates apoptosis regulated by integrins and Groucho/TLE corepressors. Cell 2004; 116; 751–762.
- 41 Cui P, Qin B, Liu N, Pan G, Pei D. Nuclear localization of the phosphatidylserine receptor protein via multiple nuclear localization signals. Exp. Cell Res. 2004; 293; 154–163.
- 42 Gruss OJ, Wittmann M, Yokoyama H et al. Chromosome-induced microtubule assembly mediated by TPX2 is required for spindle formation in HeLa cells. Nat. Cell Biol. 2002; 4; 871–879.
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