Skip to main content

Advertisement

Log in

Metabolomics approach for predicting response to neoadjuvant chemotherapy for colorectal cancer

  • Original Article
  • Published:
Metabolomics Aims and scope Submit manuscript

Abstract

Introduction

Colorectal cancer (CRC) is a clinically heterogeneous disease, which necessitates a variety of treatments and leads to different outcomes. Only some CRC patients will benefit from neoadjuvant chemotherapy (NACT).

Objectives

An accurate prediction of response to NACT in CRC patients would greatly facilitate optimal personalized management, which could improve their long-term survival and clinical outcomes.

Methods

In this study, plasma metabolite profiling was performed to identify potential biomarker candidates that can predict response to NACT for CRC. Metabolic profiles of plasma from non-response (n = 30) and response (n = 27) patients to NACT were studied using UHPLC–quadruple time-of-flight)/mass spectrometry analyses and statistical analysis methods.

Results

The concentrations of nine metabolites were significantly different when comparing response to NACT. The area under the receiver operating characteristic curve value of the potential biomarkers was up to 0.83 discriminating the non-response and response group to NACT, superior to the clinical parameters (carcinoembryonic antigen and carbohydrate antigen 199).

Conclusion

These results show promise for larger studies that could result in more personalized treatment protocols for CRC patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

CRC:

Colorectal cancer

NACT:

Neoadjuvant chemotherapy

MRI:

Magnetic resonance imaging

CEA:

Carcinoembryonic antigen

CA199:

Carbohydrate antigen 199

NMR:

Nuclear magnetic resonance

MS:

Mass spectrometry

TNM:

Tumor–node–metastasis

QC:

Quality control

QTOF:

Quadruple time-of-flight

RT:

Retention time

m/z:

Mass-to-charge ratio

PCA:

Principal component analysis

PLS-DA:

Partial least-squares discriminant analysis

VIP:

Variable importance in the projection

AUC:

Area under the receiver operating characteristic curve

RF:

Random forest

References

  • Balage, M., Dupont, J., Mothe-Satney, I., Tesseraud, S., Mosoni, L., & Dardevet, D. (2011). Leucine supplementation in rats induced a delay in muscle IR/PI3K signaling pathway associated with overall impaired glucose tolerance. The Journal of Nutritional Biochemistry, 22, 219–226.

    Article  CAS  PubMed  Google Scholar 

  • Benjamini, Y. (2010). Discovering the false discovery rate. Journal of the Royal Statistical Society, 72, 405–416.

    Article  Google Scholar 

  • Derdak, Z., Mark, N. M., Beldi, G., Robson, S. C., Wands, J. R., & Baffy, G. (2008). The mitochondrial uncoupling protein-2 promotes chemoresistance in cancer cells. Cancer Research, 68, 2813–2819.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duffy, M. J. (2001). Carcinoembryonic antigen as a marker for colorectal cancer: Is it clinically useful? Clinical Chemistry, 47, 624–630.

    CAS  PubMed  Google Scholar 

  • Dzik-Jurasz, A., et al. (2002). Diffusion MRI for prediction of response of rectal cancer to chemoradiation. The Lancet, 360, 307–308.

    Article  Google Scholar 

  • Edge, S. B., & Compton, C. C. (2010). The American Joint Committee on Cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Annals of Surgical Oncology, 17, 1471–1474. https://doi.org/10.1245/s10434-010-0985-4.

    Article  PubMed  Google Scholar 

  • Ferlay, J., et al. (2015). Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. International Journal of Cancer, 136, E359–E386.

    Article  CAS  PubMed  Google Scholar 

  • Glynne-Jones, R., Anyamene, N., Moran, B., & Harrison, M. (2012). Neoadjuvant chemotherapy in MRI-staged high-risk rectal cancer in addition to or as an alternative to preoperative chemoradiation? Annals of Oncology, 23, 2517–2526.

    Article  CAS  PubMed  Google Scholar 

  • Hinault, C., Van Obberghen, E., & Mothe-Satney, I. (2006). Role of amino acids in insulin signaling in adipocytes and their potential to decrease insulin resistance of adipose tissue. The Journal of Nutritional Biochemistry, 17, 374–378.

    Article  CAS  PubMed  Google Scholar 

  • Hou, Y., et al. (2014). A metabolomics approach for predicting the response to neoadjuvant chemotherapy in cervical cancer patients. Molecular Biosystems, 10, 2126–2133.

    Article  CAS  PubMed  Google Scholar 

  • Kuhl, C., Tautenhahn, R., Bottcher, C., Larson, T. R., & Neumann, S. (2012). CAMERA: An integrated strategy for compound spectra extraction and annotation of liquid chromatography/mass spectrometry data sets. Analytical Chemistry, 84, 283–289. https://doi.org/10.1021/ac202450g.

    Article  CAS  PubMed  Google Scholar 

  • Li, F., et al. (2013). Lipid profiling for early diagnosis and progression of colorectal cancer using direct-infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. Rapid Communications in Mass Spectrometry, 27, 24–34. https://doi.org/10.1002/rcm.6420.

    Article  CAS  PubMed  Google Scholar 

  • Liesenfeld, D. B., et al. (2015). Changes in urinary metabolic profiles of colorectal cancer patients enrolled in a prospective cohort study (ColoCare). Metabolomics, 11, 998–1012. https://doi.org/10.1007/s11306-014-0758-3.

    Article  CAS  PubMed  Google Scholar 

  • Liu, J. J., Huang, B., & Hooi, S. C. (2006). Acetyl-keto-β-boswellic acid inhibits cellular proliferation through a p21-dependent pathway in colon cancer cells. British Journal of Pharmacology, 148, 1099–1107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, J.-J., Nilsson, Å, Oredsson, S., Badmaev, V., Zhao, W.-Z., & Duan, R.-D. (2002). Boswellic acids trigger apoptosis via a pathway dependent on caspase-8 activation but independent on Fas/Fas ligand interaction in colon cancer HT-29 cells. Carcinogenesis, 23, 2087–2093.

    Article  CAS  PubMed  Google Scholar 

  • Nicholson, J. K., & Lindon, J. C. (2008). Systems biology: Metabonomics. Nature, 455, 1054.

    Article  CAS  PubMed  Google Scholar 

  • Pang, X., et al. (2009). Acetyl-11-keto-β-boswellic acid inhibits prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis. Cancer Research, 69, 5893–5900.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qiu, Y., et al. (2014). A distinct metabolic signature of human colorectal cancer with prognostic potential. Clinical Cancer Research, 20, 2136–2146. https://doi.org/10.1158/1078-0432.ccr-13-1939.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rosenthal, D. I., et al. (2008). Phase I study of preoperative radiation therapy with concurrent infusional 5-fluorouracil and oxaliplatin followed by surgery and postoperative 5-fluorouracil plus leucovorin for T3/T4 rectal adenocarcinoma: ECOG E1297. International Journal of Radiation Oncology* Biology* Physics, 72, 108–113.

    Article  CAS  Google Scholar 

  • Salvador, J. A., Moreira, V. M., Gonçalves, B. M., Leal, A. S., & Jing, Y. (2012). Ursane-type pentacyclic triterpenoids as useful platforms to discover anticancer drugs. Natural Product Reports, 29, 1463–1479.

    Article  CAS  PubMed  Google Scholar 

  • Schrag, D., et al. (2014). Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer: A pilot trial. Journal of Clinical Oncology, 32, 513.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shah, B. A., Qazi, G. N., & Taneja, S. C. (2009). Boswellic acids: A group of medicinally important compounds. Natural Product Reports, 26, 72–89.

    Article  CAS  PubMed  Google Scholar 

  • Smith, C. A., Want, E. J., O’Maille, G., Abagyan, R., & Siuzdak, G. (2006). XCMS: Processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification. Analytical Chemistry, 78, 779–787. https://doi.org/10.1021/ac051437y.

    Article  CAS  PubMed  Google Scholar 

  • Spratlin, J. L., Serkova, N. J., & Eckhardt, S. G. (2009). Clinical applications of metabolomics in oncology: a review. Clinical Cancer Research, 15, 431–440.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, J., et al. (2016). Serum metabolomics for early diagnosis of esophageal squamous cell carcinoma by UHPLC–QTOF/MS. Metabolomics, 12, 116.

    Article  CAS  Google Scholar 

  • Wei, S., et al. (2013). Metabolomics approach for predicting response to neoadjuvant chemotherapy for breast cancer. Molecular Oncology, 7, 297–307.

    Article  CAS  PubMed  Google Scholar 

  • Zheng, Z.-X., Zheng, R.-S., Zhang, S.-W., & Chen, W.-Q. (2013). Colorectal cancer incidence and mortality in China, 2010. Asian Pacific Journal of Cancer Prevention, 15, 8455–8460.

    Article  Google Scholar 

  • Zhu, J., et al. (2014). Colorectal cancer detection using targeted serum metabolic profiling. Journal of Proteome Research, 13, 4120–4130. https://doi.org/10.1021/pr500494u.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was funded by National Natural Science Foundation of China (Grant Numbers 81773551, 81473072) and Health and Family Planning Commission of Heilongjiang Province Scientific Program (Grant Number 2014-349).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Kang Li, Bin-bin Cui or Zheng-Jiang Zhu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the Ethical Standards of the Institutional and/or National Research Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 93 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, K., Zhang, F., Han, P. et al. Metabolomics approach for predicting response to neoadjuvant chemotherapy for colorectal cancer. Metabolomics 14, 110 (2018). https://doi.org/10.1007/s11306-018-1406-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11306-018-1406-0

Keywords

Navigation