Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Tumor Biology
Published in: Tumor Biology 4/2016

01-04-2016 | Original Article

Mitotic arrest deficient-like 1 is correlated with poor prognosis in small-cell lung cancer after surgical resection

Authors: Dandan Li, Qingwei Meng, Huijuan Zhang, Ting Feng, Meiyan Liu, Li Cai

Published in: Tumor Biology | Issue 4/2016

Login to get access

Abstract

Mitotic arrest deficient-like 1 (MAD1L1) whose dysfunction is associated with chromosomal instability plays a pathogenic role in a few human cancers. However, the status of MAD1L1 expression in small-cell lung cancer (SCLC) remains unknown. Immunohistochemistry was used to determine the expression of MAD1L1 protein in 32 lymph node metastasis (LN-M) tissues and 88 primary SCLCs compared with 32 adjacent noncancerous tissues. The associations of MAD1L1 protein expression with the clinicopathologic features and clinical outcomes in patients with SCLC were analyzed. The ratio of MAD1L1 positive expression was higher in primary SCLC tissues (39.8 %) and LN-M tissues (46.9 %) compared with adjacent noncancerous tissues (9.4 %). MAD1L1 positive expression was associated with tumor-node-metastasis (TNM) stage (P = 0.003), International Association for the Study of Lung Cancer (IASLC) stage (P = 0.004), tumor size (P = 0.015), lymph node metastasis (P = 0.014), and recurrence (P < 0.001). Multivariate analysis suggested that MAD1L1 positive expression was an independent factor for overall survival (hazard ratio (HR) 2.002; 95 % confidence interval (CI) 1.065–3.763; P = 0.031) and recurrence-free survival (HR 2.263; 95 % CI 1.197–4.276; P = 0.012). To sum up, MAD1L1 positive expression may be associated with tumour progression and metastasis in SCLCs and may thus serve as a new biomarker for prognosis in these patients.
Literature
1.
2.
Devesa SS, Bray F, Vizcaino AP, Parkin DM. International lung cancer trends by histologic type: male:female differences diminishing and adenocarcinoma rates rising. Int J Cancer. 2005;117:294–9.CrossRefPubMed
3.
Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol. 2006;24:4539–44.CrossRefPubMed
4.
Tartarone A, Lerose R, Ardito R, Troiani L, Tedesco B, Bozza G, et al. Long-term survival in small cell lung cancer: a case report and review of the literature. Future Oncol. 2014;10:523–8.CrossRefPubMed
5.
Pillai RN, Owonikoko TK. Small cell lung cancer: therapies and targets. Semin Oncol. 2014;41:133–42.CrossRefPubMed
6.
7.
Ma M, Wang M, Xu Y, Hu K, Liu H, Li L, et al. First-line chemotherapy and its survival analysis of 394 patients with extensive-stage small cell lung cancer in a single institute. Zhongguo Fei Ai Za Zhi. 2014;17:8–14.PubMed
8.
Pleasance ED, Stephens PJ, O’Meara S, McBride DJ, Meynert A, Jones D, et al. A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature. 2010;463:184–90.CrossRefPubMed
9.
Tahir SK, Yang X, Anderson MG, Morgan-Lappe SE, Sarthy AV, Chen J, et al. Influence of Bcl-2 family members on the cellular response of small-cell lung cancer cell lines to ABT-737. Cancer Res. 2007;67:1176–83.CrossRefPubMed
10.
Voortman J, Lee JH, Killian JK, Suuriniemi M, Wang Y, Lucchi M, et al. Array comparative genomic hybridization-based characterization of genetic alterations in pulmonary neuroendocrine tumors. Proc Natl Acad Sci U S A. 2010;107:13040–5.CrossRefPubMedPubMedCentral
11.
Jin DY, Spencer F, Jeang KT. Human T cell leukemia virus type 1 oncoprotein Tax targets the human mitotic checkpoint protein MAD1. Cell. 1998;93:81–91.CrossRefPubMed
12.
Tsukasaki K, Miller CW, Greenspun E, Eshaghian S, Kawabata H, Fujimoto T, et al. Mutations in the mitotic check point gene, MAD1L1, in human cancers. Oncogene. 2001;20:3301–5.CrossRefPubMed
13.
Yuan B, Xu Y, Woo JH, Wang Y, Bae YK, Yoon DS, et al. Increased expression of mitotic checkpoint genes in breast cancer cells with chromosomal instability. Clin Cancer Res. 2006;12:405–10.CrossRefPubMed
14.
Han S, Park K, Kim HY, Lee MS, Kim HJ, Kim YD, et al. Clinical implication of altered expression of Mad1 protein in human breast carcinoma. Cancer. 2000;88:1623–32.CrossRefPubMed
15.
Nomoto S, Haruki N, Takahashi T, Masuda A, Koshikawa T, Takahashi T, et al. Search for in vivo somatic mutations in the mitotic checkpoint gene, hMAD1, in human lung cancers. Oncogene. 1999;18:7180–3.CrossRefPubMed
16.
Guo Y, Zhang X, Yang M, Miao X, Shi Y, Yao J, et al. Functional evaluation of missense variations in the human MAD1L1 and MAD2L1 genes and their impact on susceptibility to lung cancer. J Med Genet. 2010;47:616–22.CrossRefPubMed
17.
Coe BP, Lee EH, Chi B, Girard L, Minna JD, Gazdar AF, et al. Gain of a region on 7p22.3, containing MAD1L1, is the most frequent event in small-cell lung cancer cell lines. Genes Chromosom Cancer. 2006;45:11–9.CrossRefPubMed
18.
Sun Q, Zhang X, Liu T, Liu X, Geng J, He X, et al. Increased expression of mitotic arrest deficient-like 1 (MAD1L1) is associated with poor prognosis and insensitive to taxol treatment in breast cancer. Breast Cancer Res Treat. 2013;140:323–30.CrossRefPubMed
19.
Kienitz A, Vogel C, Morales I, Müller R, Bastians H. Partial downregulation of MAD1 causes spindle checkpoint inactivation and aneuploidy, but does not confer resistance towards taxol. Oncogene. 2005;24:4301–10.CrossRefPubMed
20.
Tsukasaki K, Imaizumi Y, Tawara M, Fujimoto T, Fukushima T, Hata T, et al. Diversity of leukaemic cell morphology in ATL correlates with prognostic factors, aberrant immunophenotype and defective HTLV-1 genotype. Br J Haematol. 1999;105:369–75.CrossRefPubMed
21.
Chun AC, Jin DY. Transcriptional regulation of mitotic checkpoint gene MAD1 by p53. J Biol Chem. 2003;278:37439–50.CrossRefPubMed
22.
Iwanaga Y, Jeang KT. Expression of mitotic spindle checkpoint protein hsMAD1 correlates with cellular proliferation and is activated by a gain-of-function p53 mutant. Cancer Res. 2002;62:2618–24.PubMed
23.
Nam CW, Park NH, Park BR, Shin JW, Jung SW, Na YW, et al. Mitotic checkpoint gene MAD1 in hepatocellular carcinoma is associated with tumor recurrence after surgical resection. J Surg Oncol. 2008;97:567–71.CrossRefPubMed
24.
Zou L, Zhang P, Luo C, Tu Z. Mad1 suppresses bladder cancer cell proliferation by inhibiting human telomerase reverse transcriptase transcription and telomerase activity. Urology. 2006;67:1335–40.CrossRefPubMed
25.
Osaki M, Inoue T, Yamaguchi S, Inaba A, Tokuyasu N, Jeang KT, et al. MAD1 (mitotic arrest deficiency 1) is a candidate for a tumor suppressor gene in human stomach. Virchows Arch. 2007;451:771–9.CrossRefPubMed
26.
Bhattacharjya S, Nath S, Ghose J, Maiti GP, Biswas N, Bandyopadhyay S, et al. miR-125b promotes cell death by targeting spindle assembly checkpoint gene MAD1 and modulating mitotic progression. Cell Death Differ. 2013;20:430–42.CrossRefPubMed
27.
Rottmann S, Menkel AR, Bouchard C, Mertsching J, Loidl P, Kremmer E, et al. Mad1 function in cell proliferation and transcriptional repression is antagonized by cyclin E/CDK2. J Biol Chem. 2005;280:15489–92.CrossRefPubMed
28.
Chen Y, Yeh PC, Huang JC, Yeh CC, Juang YL. The spindle checkpoint protein MAD1 regulates the expression of E-cadherin and prevents cell migration. Oncol Rep. 2012;27:487–91.PubMed
29.
Rottmann S, Lüscher B. The Mad side of the Max network: antagonizing the function of Myc and more. Curr Top Microbiol Immunol. 2006;302:63–122.PubMed
Metadata
Title
Mitotic arrest deficient-like 1 is correlated with poor prognosis in small-cell lung cancer after surgical resection
Authors
Dandan Li
Qingwei Meng
Huijuan Zhang
Ting Feng
Meiyan Liu
Li Cai
Publication date
01-04-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 4/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4302-5

Other articles of this Issue 4/2016

Tumor Biology 4/2016 Go to the issue

Original Article

Lymphocyte to monocyte ratio is associated with response to first-line platinum-based chemotherapy and prognosis of early-stage non-small cell lung cancer patients

Original Article

Simple laboratory score improves the preoperative diagnosis of adnexal mass

Original Article

The potential role of PHF6 as an oncogene: a genotranscriptomic/proteomic meta-analysis

Original Article

Involvement of Numb-mediated HIF-1α inhibition in anti-proliferative effect of PNA-antimiR-182 in trastuzumab-sensitive and -resistant SKBR3 cells

Original Article

Coexpression of CXCR4 and MMP9 predicts lung metastasis and poor prognosis in resected osteosarcoma

Original Article

Novel MicroRNA signatures in HPV-mediated cervical carcinogenesis in Indian women
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits