Skip to main content
Top
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Association of decreased mitochondrial DNA content with the progression of colorectal cancer

Authors: HaiHong Cui, Ping Huang, ZhiJing Wang, YunXin Zhang, ZhenHua Zhang, Wei Xu, XiaoPeng Wang, Ying Han, XiaoMing Guo

Published in: BMC Cancer | Issue 1/2013

Login to get access

Abstract

Background

Experimental data suggest that mitochondria is involved in tumorigenesis. However, little is known about the qualitative and quantitative changes of mtDNA in colorectal cancer tissues. We therefore conducted possible correlations of the mitochondrial DNA (mtDNA) copy number in colorectal cancer (CRC) with clinical and pathological findings and CRC prognosis.

Methods

mtDNA copy numbers in CRC cancer tissue and adjacent non-cancerous tissue samples were measured using quantitative real-time polymerase chain reaction analyses from 60 patients admitted to our hospital. We examined the correlation of mtDNA copy numbers and clinicopathologic parameters of CRC patients. The correlation between mtDNA copy number and three-year survival was analyzed.

Results

The mtDNA copy number was lower in CRC tissue compared with the corresponding non-cancerous colorectal tissue (mean: 108.60 ± 20.11 vs. 153.68 ± 25.72) and was significantly correlated with lymph-node metastasis. Patients with a lower mtDNA copy number tended to have lower 3-year survival than patients with a higher mtDNA copy number assessed by Kaplan–Meier curves, but the correlation was not significant (overall survival, 63.0 vs 83%).

Conclusions

These results suggest that a reduced copy number of mtDNA is correlated with malignant potential in CRC.
Appendix
Available only for authorised users
Literature
1.
go back to reference Scarpulla RC: Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev. 2008, 88: 611-638. 10.1152/physrev.00025.2007.CrossRefPubMed Scarpulla RC: Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev. 2008, 88: 611-638. 10.1152/physrev.00025.2007.CrossRefPubMed
2.
go back to reference Gredilla R, Bohr VA, Stevnsner T: Mitochondrial DNA repair and association with aging—an update. Exp Gerontol. 2010, 45: 478-488. 10.1016/j.exger.2010.01.017.CrossRefPubMedPubMedCentral Gredilla R, Bohr VA, Stevnsner T: Mitochondrial DNA repair and association with aging—an update. Exp Gerontol. 2010, 45: 478-488. 10.1016/j.exger.2010.01.017.CrossRefPubMedPubMedCentral
3.
go back to reference Janakiram NB, Rao CV: Molecular markers and targets for colorectal cancer prevention. Acta Pharmacol Sin. 2008, 29: 1-20. 10.1111/j.1745-7254.2008.00742.x.CrossRefPubMed Janakiram NB, Rao CV: Molecular markers and targets for colorectal cancer prevention. Acta Pharmacol Sin. 2008, 29: 1-20. 10.1111/j.1745-7254.2008.00742.x.CrossRefPubMed
4.
go back to reference Alberts SR, Wagman LD: Chemotherapy for colorectal cancer liver metastases. Oncologist. 2008, 13: 1063-1073. 10.1634/theoncologist.2008-0142.CrossRefPubMed Alberts SR, Wagman LD: Chemotherapy for colorectal cancer liver metastases. Oncologist. 2008, 13: 1063-1073. 10.1634/theoncologist.2008-0142.CrossRefPubMed
5.
go back to reference Miller FJ, Rosenfeldt FL, Zhang C, Linnane AW, Nagley P: Precise determination of mitochondrial DNA copy number in human skeletal and cardiac muscle by a PCR-based assay: lack of change of copy number with age. Nucleic Acids Res. 2003, 31: e61-10.1093/nar/gng060.CrossRefPubMedPubMedCentral Miller FJ, Rosenfeldt FL, Zhang C, Linnane AW, Nagley P: Precise determination of mitochondrial DNA copy number in human skeletal and cardiac muscle by a PCR-based assay: lack of change of copy number with age. Nucleic Acids Res. 2003, 31: e61-10.1093/nar/gng060.CrossRefPubMedPubMedCentral
6.
go back to reference Schatz G: The magic garden. Annu Rev Biochem. 2007, 76: 673-678. 10.1146/annurev.biochem.76.060806.091141.CrossRefPubMed Schatz G: The magic garden. Annu Rev Biochem. 2007, 76: 673-678. 10.1146/annurev.biochem.76.060806.091141.CrossRefPubMed
7.
go back to reference Singh KK, Russell J, Sigala B, Zhang Y, Williams J, Keshav KF: Mitochondrial DNA determines the cellular response to cancer therapeutic agents. Oncogene. 1999, 18: 6641-6646. 10.1038/sj.onc.1203056.CrossRefPubMed Singh KK, Russell J, Sigala B, Zhang Y, Williams J, Keshav KF: Mitochondrial DNA determines the cellular response to cancer therapeutic agents. Oncogene. 1999, 18: 6641-6646. 10.1038/sj.onc.1203056.CrossRefPubMed
8.
go back to reference Barrientos A, Casademont J, Cardellach F: Ruduced steady-state levels of mitochondrial RNA and increased mitochondrial DNA in human brain with aging. Mol Brain Res. 1997, 52: 284-289. 10.1016/S0169-328X(97)00278-7.CrossRefPubMed Barrientos A, Casademont J, Cardellach F: Ruduced steady-state levels of mitochondrial RNA and increased mitochondrial DNA in human brain with aging. Mol Brain Res. 1997, 52: 284-289. 10.1016/S0169-328X(97)00278-7.CrossRefPubMed
9.
go back to reference Lee HC, Yin PH, Lu CY: Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells. Biochem J. 2000, 348: 425-432. 10.1042/0264-6021:3480425.CrossRefPubMedPubMedCentral Lee HC, Yin PH, Lu CY: Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells. Biochem J. 2000, 348: 425-432. 10.1042/0264-6021:3480425.CrossRefPubMedPubMedCentral
10.
11.
go back to reference Modica-Napolitano JS, Kulawiec M, Singh KK: Mitochondria and human cancer. Curr Mol Med. 2007, 7 (1): 121-131. 10.2174/156652407779940495.CrossRefPubMed Modica-Napolitano JS, Kulawiec M, Singh KK: Mitochondria and human cancer. Curr Mol Med. 2007, 7 (1): 121-131. 10.2174/156652407779940495.CrossRefPubMed
12.
go back to reference Wang Y, Liu VW, Xue WC, Tsang PC, Cheung AN, Ngan HY: The increase of mitochondrial DNA content in endometrial adenocarcinoma cells: a quantitative study using laser-captured microdissected tissues. Gynecol Oncol. 2005, 98 (1): 104-110. 10.1016/j.ygyno.2005.04.015.CrossRefPubMed Wang Y, Liu VW, Xue WC, Tsang PC, Cheung AN, Ngan HY: The increase of mitochondrial DNA content in endometrial adenocarcinoma cells: a quantitative study using laser-captured microdissected tissues. Gynecol Oncol. 2005, 98 (1): 104-110. 10.1016/j.ygyno.2005.04.015.CrossRefPubMed
13.
go back to reference Jeon JP, Shim SM, Nam HY, Baik SY, Kim JW, Han BG: Copy number increase of 1p36.33 and mitochondrial genome amplification in Epstein-Barr virus-transformed lymphoblastoid cell lines. Cancer Genet Cytogenet. 2007, 173 (2): 122-130. 10.1016/j.cancergencyto.2006.10.010.CrossRefPubMed Jeon JP, Shim SM, Nam HY, Baik SY, Kim JW, Han BG: Copy number increase of 1p36.33 and mitochondrial genome amplification in Epstein-Barr virus-transformed lymphoblastoid cell lines. Cancer Genet Cytogenet. 2007, 173 (2): 122-130. 10.1016/j.cancergencyto.2006.10.010.CrossRefPubMed
14.
go back to reference Lee W, Choi HI, Kim MJ, Park SY: Depletion of mitochondrial DNA up-regulates the expression of MDR1 gene via an increase in mRNA stability. Exp Mol Med. 2008, 40 (1): 109-117. 10.3858/emm.2008.40.1.109.CrossRefPubMedPubMedCentral Lee W, Choi HI, Kim MJ, Park SY: Depletion of mitochondrial DNA up-regulates the expression of MDR1 gene via an increase in mRNA stability. Exp Mol Med. 2008, 40 (1): 109-117. 10.3858/emm.2008.40.1.109.CrossRefPubMedPubMedCentral
15.
go back to reference Lee HC, Hsu LS, Yin PH, Lee LM, Chi CW: Heteroplasmic mutation of mitochondrial DNA D-loop and 4977-bp deletion in human cancer cells during mitochondrial DNA depletion. Mitochondrion. 2007, 7 (1–2): 157-163.CrossRefPubMed Lee HC, Hsu LS, Yin PH, Lee LM, Chi CW: Heteroplasmic mutation of mitochondrial DNA D-loop and 4977-bp deletion in human cancer cells during mitochondrial DNA depletion. Mitochondrion. 2007, 7 (1–2): 157-163.CrossRefPubMed
16.
go back to reference Yamada S, Nomoto S, Fujii T, Kaneko T, Takeda S, Inoue S, Kanazumi N, Nakao A: Correlation between copy number of mitochondrial DNA and clinico-pathologic parameters of hepatocellular carcinoma. Eur J Surg Oncol. 2006, 32 (3): 303-307. 10.1016/j.ejso.2006.01.002.CrossRefPubMed Yamada S, Nomoto S, Fujii T, Kaneko T, Takeda S, Inoue S, Kanazumi N, Nakao A: Correlation between copy number of mitochondrial DNA and clinico-pathologic parameters of hepatocellular carcinoma. Eur J Surg Oncol. 2006, 32 (3): 303-307. 10.1016/j.ejso.2006.01.002.CrossRefPubMed
17.
go back to reference Amuthan G, Biswas G, Zhang SY, Klein-Szanto A, Vijayasarathy C, Avadhani NG: Mitochondria-to-nucleus stress signaling induces phenotypic changes, tumor progression and cell invasion. EMBO J. 2001, 20 (8): 1910-1920. 10.1093/emboj/20.8.1910.CrossRefPubMedPubMedCentral Amuthan G, Biswas G, Zhang SY, Klein-Szanto A, Vijayasarathy C, Avadhani NG: Mitochondria-to-nucleus stress signaling induces phenotypic changes, tumor progression and cell invasion. EMBO J. 2001, 20 (8): 1910-1920. 10.1093/emboj/20.8.1910.CrossRefPubMedPubMedCentral
18.
go back to reference Wu CW, Yin PH, Hung WY, Li AF, Li SH, Chi CW, Wei YH, Lee HC: Mitochondrial DNA mutations and mitochondrial DNA depletion in gastric cancer. Genes Chromosomes Cancer. 2005, 44 (1): 19-28. 10.1002/gcc.20213.CrossRefPubMed Wu CW, Yin PH, Hung WY, Li AF, Li SH, Chi CW, Wei YH, Lee HC: Mitochondrial DNA mutations and mitochondrial DNA depletion in gastric cancer. Genes Chromosomes Cancer. 2005, 44 (1): 19-28. 10.1002/gcc.20213.CrossRefPubMed
19.
go back to reference Cook CC, Higuchi M: The awakening of an advanced malignant cancer: an insult to the mitochondrial genome. Biochim Biophys Acta. 2012, 1820 (5): 652-662. 10.1016/j.bbagen.2011.08.017.CrossRefPubMed Cook CC, Higuchi M: The awakening of an advanced malignant cancer: an insult to the mitochondrial genome. Biochim Biophys Acta. 2012, 1820 (5): 652-662. 10.1016/j.bbagen.2011.08.017.CrossRefPubMed
20.
go back to reference Gahan ME, Miller F, Lewin SR, Cherry CL, Hoy JF, Mijch A, Rosenfeldt F, Wesselingh SL: Quantification of mitochondrial DNA in peripheral blood mononuclear cells and subcutaneous fat using real-time polymerase chain reaction. J Clin Virol. 2001, 22: 241-247. 10.1016/S1386-6532(01)00195-0.CrossRefPubMed Gahan ME, Miller F, Lewin SR, Cherry CL, Hoy JF, Mijch A, Rosenfeldt F, Wesselingh SL: Quantification of mitochondrial DNA in peripheral blood mononuclear cells and subcutaneous fat using real-time polymerase chain reaction. J Clin Virol. 2001, 22: 241-247. 10.1016/S1386-6532(01)00195-0.CrossRefPubMed
21.
go back to reference Stoeltzing O, McCarty MF, Wey JS, Fan F, Liu W, Belcheva A, Bucana CD, Semenza GL, Ellis LM: Role of hypoxia-inducible factor 1alpha in gastric cancer cell growth, angiogenesis, and vessel maturation. J Natl Cancer Inst. 2004, 96: 946-956. 10.1093/jnci/djh168.CrossRefPubMed Stoeltzing O, McCarty MF, Wey JS, Fan F, Liu W, Belcheva A, Bucana CD, Semenza GL, Ellis LM: Role of hypoxia-inducible factor 1alpha in gastric cancer cell growth, angiogenesis, and vessel maturation. J Natl Cancer Inst. 2004, 96: 946-956. 10.1093/jnci/djh168.CrossRefPubMed
22.
go back to reference Derwinger K, Carlsson G, Gustavsson B: A study of lymph node ratio as a prognostic marker in colon cancer. Eur J Surg Oncol. 2008, 34: 771-775. 10.1016/j.ejso.2007.11.002.CrossRefPubMed Derwinger K, Carlsson G, Gustavsson B: A study of lymph node ratio as a prognostic marker in colon cancer. Eur J Surg Oncol. 2008, 34: 771-775. 10.1016/j.ejso.2007.11.002.CrossRefPubMed
Metadata
Title
Association of decreased mitochondrial DNA content with the progression of colorectal cancer
Authors
HaiHong Cui
Ping Huang
ZhiJing Wang
YunXin Zhang
ZhenHua Zhang
Wei Xu
XiaoPeng Wang
Ying Han
XiaoMing Guo
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-110

Other articles of this Issue 1/2013

BMC Cancer 1/2013 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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