Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
January-2018 Volume 15 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
January-2018 Volume 15 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Mutant‑allele fraction heterogeneity is associated with non‑small cell lung cancer patient survival

  • Authors:
    • Sipeng Shen
    • Yongyue Wei
    • Ruyang Zhang
    • Mulong Du
    • Weiwei Duan
    • Sheng Yang
    • Yang Zhao
    • David C. Christiani
    • Feng Chen
  • View Affiliations / Copyright

    Affiliations: Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211136, P.R. China, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA
    Copyright: © Shen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 795-802
    |
    Published online on: November 15, 2017
       https://doi.org/10.3892/ol.2017.7428
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Genetic intratumor heterogeneity is associated with tumor occurrence, development and overall outcome. The present study aims to explore the association between mutant‑allele fraction (MAF) heterogeneity and patient overall survival in lung cancer. Somatic mutation data of 939 non‑small cell lung cancer (NSCLC) cases were obtained from The Cancer Genome Atlas. Entropy‑based mutation allele fraction (EMAF) score was used to describe the uncertainty of individual somatic mutation patterns and to further analyze the association with patient overall survival. Results indicated that association between EMAF and overall survival was significant in the discovery set [hazard ratio (H)R=1.62; 95% confidence interval (CI): 1.08‑2.41; P=0.018] and replication set (HR=1.63; 95% CI: 1.11‑2.37; P=0.011). In addition, EMAF was also significantly different in lung adenocarcinoma and squamous cell carcinoma. Furthermore, a significant difference was indicated in early‑stage patients. Results from c‑index analysis indicated that EMAF improved the model predictive performance on the 3‑year survival beyond that of traditional clinical staging, particularly in early‑stage patients. In conclusion, EMAF successfully reflected MAF heterogeneity among patients with NSCLC. Additionally, EMAF improved the predictive performance in early‑stage patient prognosis beyond that of traditional clinical staging. In clinical application, EMAF appears to identify a subset of early‑stage patients with a poor prognosis and therefore may help inform clinical decisions regarding the application of chemotherapy after surgery.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Ma H, Shu Y, Pan S, Chen J, Dai J, Jin G, Hu Z and Shen H: Polymorphisms of key chemokine genes and survival of non-small cell lung cancer in Chinese. Lung Cancer. 74:164–169. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Devarakonda S, Morgensztern D and Govindan R: Genomic alterations in lung adenocarcinoma. Lancet Oncol. 16:e342–e351. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran WJ Jr, Wu YL and Paz-Ares L: Lung cancer: Current therapies and new targeted treatments. Lancet. 389:299–311. 2017. View Article : Google Scholar : PubMed/NCBI

4 

de Bruin EC, McGranahan N, Mitter R, Salm M, Wedge DC, Yates L, Jamal-Hanjani M, Shafi S, Murugaesu N, Rowan AJ, et al: Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science. 346:251–256. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Zhang J, Fujimoto J, Zhang J, Wedge DC, Song X, Zhang J, Seth S, Chow CW, Cao Y, Gumbs C, et al: Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing. Science. 346:256–259. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Håkansson L and Tropé C: On the presence within tumours of clones that differ in sensitivity to cytostatic drugs. Acta Pathol Microbiol Scand A. 82:35–40. 1974.PubMed/NCBI

7 

Nowell PC: The clonal evolution of tumor cell populations. Science. 194:23–28. 1976. View Article : Google Scholar : PubMed/NCBI

8 

Fidler IJ and Kripke ML: Metastasis results from preexisting variant cells within a malignant tumor. Science. 197:893–895. 1977. View Article : Google Scholar : PubMed/NCBI

9 

Dexter DL, Kowalski HM, Blazar BA, Fligiel Z, Vogel R and Heppner GH: Heterogeneity of tumor cells from a single mouse mammary tumor. Cancer Res. 38:3174–3181. 1978.PubMed/NCBI

10 

Heppner GH: Tumor heterogeneity. Cancer Res. 44:2259–2265. 1984.PubMed/NCBI

11 

Cooke SL, Temple J, Macarthur S, Zahra MA, Tan LT, Crawford RA, Ng CK, Jimenez-Linan M, Sala E and Brenton JD: Intra-tumour genetic heterogeneity and poor chemoradiotherapy response in cervical cancer. Br J Cancer. 104:361–368. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Navin N, Kendall J, Troge J, Andrews P, Rodgers L, McIndoo J, Cook K, Stepansky A, Levy D, Esposito D, et al: Tumourevolution inferred by single-cell sequencing. Nature. 472:90–94. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Gerlinger M, Rowan AJ, Horswell S, Math M, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, et al: Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 366:883–892. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H, Cahill DP, Nahed BV, Curry WT, Martuza RL, et al: Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 344:1396–1401. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Mroz EA and Rocco JW: MATH, a novel measure of intratumor genetic heterogeneity, is high in poor-outcome classes of head and neck squamous cell carcinoma. Oral Oncol. 49:211–215. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Mroz EA, Tward AD, Pickering CR, Myers JN, Ferris RL and Rocco JW: High intratumor genetic heterogeneity is related to worse outcome in patients with head and neck squamous cell carcinoma. Cancer. 119:3034–3042. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Mroz EA, Tward AD, Hammon RJ, Ren Y and Rocco JW: Intra-tumor genetic heterogeneity and mortality in head and neck cancer: Analysis of data from the cancer genome atlas. PLoS Med. 12:e10017862015. View Article : Google Scholar : PubMed/NCBI

18 

Rocco JW: Mutant allele tumor heterogeneity (MATH) and head and neck squamous cell carcinoma. Head Neck Pathol. 9:1–5. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Ostrer H: Changing the game with whole exome sequencing. Clin Genet. 80:101–103. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Cancer Genome Atlas Research Network, . Comprehensive molecular profiling of lung adenocarcinoma. Nature. 511:543–550. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Chapman MA, Lawrence MS, Keats JJ, Cibulskis K, Sougnez C, Schinzel AC, Harview CL, Brunet JP, Ahmann GJ, Adli M, et al: Initial genome sequencing and analysis of multiple myeloma. Nature. 471:467–472. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Broad Institute TCGA Genome Data Analysis Center, . Analysis Overview for Lung Adenocarcinoma (Primary solid tumor cohort). 28–January. 2016Broad Institute of MIT and Harvard; https://doi.org/10.7908/c18g8k472016

23 

Cheng PF, Dummer R and Levesque MP: Data mining The cancer genome atlas in the era of precision cancer medicine. Swiss Med Wkly. 145:w141832015.PubMed/NCBI

24 

Koboldt DC, Chen K, Wylie T, Larson DE, McLellan MD, Mardis ER, Weinstock GM, Wilson RK and Ding L: VarScan: Variant detection in massively parallel sequencing of individual and pooled samples. Bioinformatics. 25:2283–2285. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Yee J, Kwon MS, Park T and Park M: A modified entropy-based approach for identifying gene-gene interactions in case-control study. PLoS One. 8:e693212013. View Article : Google Scholar : PubMed/NCBI

26 

Shannon CE: The mathematical theory of communication. 1963. MD Comput. 14:306–317. 1997.PubMed/NCBI

27 

Schreiber T: Measuring information transfer. Phys Rev Lett. 85:461–464. 2000. View Article : Google Scholar : PubMed/NCBI

28 

Uno H, Cai T, Pencina MJ, D'Agostino RB and Wei LJ: On the C-statistics for evaluating overall adequacy of risk prediction procedures with censored survival data. Stat Med. 30:1105–1117. 2011.PubMed/NCBI

29 

Landau DA, Carter SL, Stojanov P, McKenna A, Stevenson K, Lawrence MS, Sougnez C, Stewart C, Sivachenko A, Wang L, et al: Evolution and impact of subclonal mutations in chronic lymphocytic leukemia. Cell. 152:714–726. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Marquette D, Pichon E, Deschasse G, Lemaire B, Lemarie E, Diot P and Marchand-Adam S: Lung cancer in adults: Better prognosis of patients aged 45 and under related to good condition and lower TNM stage (a comparative and retrospective study). Presse Med. 41:e250–e256. 2012.(In French). View Article : Google Scholar : PubMed/NCBI

31 

Liu M, Pan H, Zhang F, Zhang Y, Zhang Y, Xia H, Zhu J, Fu W and Zhang X: Identification of TNM stage-specific genes in lung adenocarcinoma by genome-wide expression profiling. Oncol Lett. 6:763–768. 2013.PubMed/NCBI

32 

Liu Y, Wang L, Lin XY, Wang J, Yu JH, Miao Y and Wang EH: The transcription factor DEC1 (BHLHE40/STRA13/SHARP-2) is negatively associated with TNM stage in non-small-cell lung cancer and inhibits the proliferation through cyclin D1 in A549 and BE1 cells. Tumour Biol. 34:1641–1650. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Yu KH, Zhang C, Berry GJ, Altman RB, Ré C, Rubin DL and Snyder M: Predicting non-small cell lung cancer prognosis by fully automated microscopic pathology image features. Nat Commun. 7:124742016. View Article : Google Scholar : PubMed/NCBI

34 

Erb CT, Su KW, Soulos PR, Tanoue LT and Gross CP: Surveillance practice patterns after curative intent therapy for stage I non-small-cell lung cancer in the medicare population. Lung Cancer. 99:200–207. 2016. View Article : Google Scholar : PubMed/NCBI

35 

Zhao T, Xu J, Liu L, Bai J, Xu C, Xiao Y, Li X and Zhang L: Identification of cancer-related lncRNAs through integrating genome, regulome and transcriptome features. MolBiosyst. 11:126–136. 2015.

36 

Koch L: Cancer genomics: Non-coding mutations in the driver seat. Nat Rev Genet. 15:574–575. 2014. View Article : Google Scholar : PubMed/NCBI

37 

Piraino SW and Furney SJ: Beyond the exome: The role of non-coding somatic mutations in cancer. Ann Oncol. 27:240–248. 2016. View Article : Google Scholar : PubMed/NCBI

38 

Tavare S: Data integration in cancer genomics: Non-coding mutations. Genet Epidemiology. 585:2015.

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Shen S, Wei Y, Zhang R, Du M, Duan W, Yang S, Zhao Y, Christiani DC and Chen F: Mutant‑allele fraction heterogeneity is associated with non‑small cell lung cancer patient survival. Oncol Lett 15: 795-802, 2018.
APA
Shen, S., Wei, Y., Zhang, R., Du, M., Duan, W., Yang, S. ... Chen, F. (2018). Mutant‑allele fraction heterogeneity is associated with non‑small cell lung cancer patient survival. Oncology Letters, 15, 795-802. https://doi.org/10.3892/ol.2017.7428
MLA
Shen, S., Wei, Y., Zhang, R., Du, M., Duan, W., Yang, S., Zhao, Y., Christiani, D. C., Chen, F."Mutant‑allele fraction heterogeneity is associated with non‑small cell lung cancer patient survival". Oncology Letters 15.1 (2018): 795-802.
Chicago
Shen, S., Wei, Y., Zhang, R., Du, M., Duan, W., Yang, S., Zhao, Y., Christiani, D. C., Chen, F."Mutant‑allele fraction heterogeneity is associated with non‑small cell lung cancer patient survival". Oncology Letters 15, no. 1 (2018): 795-802. https://doi.org/10.3892/ol.2017.7428
Copy and paste a formatted citation
x
Spandidos Publications style
Shen S, Wei Y, Zhang R, Du M, Duan W, Yang S, Zhao Y, Christiani DC and Chen F: Mutant‑allele fraction heterogeneity is associated with non‑small cell lung cancer patient survival. Oncol Lett 15: 795-802, 2018.
APA
Shen, S., Wei, Y., Zhang, R., Du, M., Duan, W., Yang, S. ... Chen, F. (2018). Mutant‑allele fraction heterogeneity is associated with non‑small cell lung cancer patient survival. Oncology Letters, 15, 795-802. https://doi.org/10.3892/ol.2017.7428
MLA
Shen, S., Wei, Y., Zhang, R., Du, M., Duan, W., Yang, S., Zhao, Y., Christiani, D. C., Chen, F."Mutant‑allele fraction heterogeneity is associated with non‑small cell lung cancer patient survival". Oncology Letters 15.1 (2018): 795-802.
Chicago
Shen, S., Wei, Y., Zhang, R., Du, M., Duan, W., Yang, S., Zhao, Y., Christiani, D. C., Chen, F."Mutant‑allele fraction heterogeneity is associated with non‑small cell lung cancer patient survival". Oncology Letters 15, no. 1 (2018): 795-802. https://doi.org/10.3892/ol.2017.7428
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team