Tumor Biology

, Volume 36, Issue 6, pp 4253–4260 | Cite as

Extracellular cytochrome c as a biomarker for monitoring therapeutic efficacy and prognosis of non-small cell lung cancer patients

  • Jamsheed Javid
  • Rashid Mir
  • P. K. Julka
  • P. C. Ray
  • Alpana Saxena
Research Article

Abstract

Non-small cell lung cancer has a devastating prognosis, and markers enabling a precise prediction of therapy response have long remained scarce. Better treatment monitoring would allow an individual’s more effective patient adjusted therapy with lesser side effects and good clinical outcomes. In the present study, we monitored the serum cytochrome c levels pre- and post-chemotherapy of non-small cell lung cancer patients. Using highly sensitive enzyme-linked immunosorbent assay, we evaluated cytochrome c levels in serum of 100 non-small cell lung cancer and 100 healthy controls. We observed about threefold lower serum cytochrome c level in newly diagnosed non-small cell lung cancer patients than healthy individuals. Patients in advanced stages and grade 3 histological differentiation showed significantly low level of serum cytochrome c, and the lower levels were associated with worse survival outcome of non-small cell lung cancer patients. In addition, serum cytochrome c level was observed to be more than 13-fold higher after first cycle of conventional chemotherapy, wherein patients with higher level of serum cytochrome c before any therapy showed better response to chemotherapy in terms of significantly higher level of serum cytochrome c after first cycle of chemotherapy than patients with low level of serum cytochrome c at the time of diagnosis. Detection of serum cytochrome c levels at the time of diagnosis may be useful in suggesting disease severity and prognosis of the non-small cell lung cancer patients. Monitoring of serum cytochrome c might also serve as a sensitive apoptotic marker in vivo reflecting chemotherapy-induced cell death burden in patients with non-small cell lung cancer.

Keywords

Serum cytochrome c Biomarker Chemotherapy Non-small cell lung cancer patients 

Abbreviations

NSCLC

Non-small cell lung cancer

SCC

Squamous cell carcinoma

ADC

Adenocarcinoma

Notes

Acknowledgments

The authors specially thank all of the patients who participated in this study.

Conflicts of interest

None

References

  1. 1.
    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.CrossRefPubMedGoogle Scholar
  2. 2.
    Dikshit R, Gupta PC, Ramasundarahettige C, Gajalakshmi V, Aleksandrowicz L, Badwe R. Cancer mortality in India: a nationally representative survey. Lancet. 2012;379(9828):1807–16.CrossRefPubMedGoogle Scholar
  3. 3.
    Lung Cancer: Survival Rates and Prognosis. National cancer Institute. 2012. http://www.cancer.gov/cancertopics/types/lung/cancer-survival-prognosis. Accessed 10 May 2012.
  4. 4.
    Cain K, Bratton SB, Langlais C, Walker G, Brown DG, Sun XM, et al. Apaf-1 oligomerizes into biologically active ~700-kDa and inactive ~1.4-MDa apoptosome complexes. J Biol Chem. 2000;275:6067–70.CrossRefPubMedGoogle Scholar
  5. 5.
    Ahlemeyer B, Klumpp S, Krieglstein J. Release of cytochrome c into the extracellular space contributes to neuronal apoptosis induced by staurosporine. Brain Res. 2002;934(2):107–16.CrossRefPubMedGoogle Scholar
  6. 6.
    Renz A, Berdel WE, Kreuter M, Belka C, Schulze-Osthoff K, Los M. Rapid extracellular release of cytochrome c is specific for apoptosis and marks cell death in vivo. Blood. 2001;98(5):1542–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Barczyk K, Kreuter M, Pryjma J, Booy EP, Maddika S, Ghavami S, et al. Serum cytochrome c indicates in vivo apoptosis and can serve as a prognostic marker during cancer therapy. Int J Cancer. 2005;116(2):167–73.CrossRefPubMedGoogle Scholar
  8. 8.
    Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. CHEST. 2009;136:260–71.CrossRefPubMedGoogle Scholar
  9. 9.
    Osaka A, Hasegawa H, Tsuruda K, Inokuchi N, Yanagihara K, Yamada Y, et al. Serum cytochrome c to indicate the extent of ongoing tumor cell death. Int J Lab Hematol. 2009;31(3):307–14.CrossRefPubMedGoogle Scholar
  10. 10.
    Renz A, Burek C, Mier W, Mozoluk M, Schulze, Osthoff K, et al. Cytochrome c is rapidly extruded from apoptotic cells and detectable in serum of anticancer drug treated tumor patients. Adv Exp Med Biol. 2001;495:331–4.CrossRefPubMedGoogle Scholar
  11. 11.
    Nilay K, Alka J, Jeremy W, Beamer BA, Fedarko NS. Serum markers of apoptosis decrease with age and cancer stage. AGING. 2009;1(7):652–63.CrossRefGoogle Scholar
  12. 12.
    Akemi O, Hiroo H, Yasuaki Y, Katsunori Y, Tomayoshi H, Mariko M, et al. A novel role of serum cytochrome c as a tumor marker in patients with operable cancer. J Cancer Res Clin Oncol. 2009;135:371–7.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Jamsheed Javid
    • 1
  • Rashid Mir
    • 1
  • P. K. Julka
    • 2
  • P. C. Ray
    • 1
  • Alpana Saxena
    • 1
  1. 1.Department of BiochemistryMaulana Azad Medical College and Associated hospitalsNew DelhiIndia
  2. 2.Department of Radiotherapy and OncologyAll India Institute of Medical SciencesNew DelhiIndia

Personalised recommendations