Top

Clinical and Translational Oncology

Published in:

01-03-2017 | Research Article

M30/M65 ratio predicts the outcome of paclitaxel chemotherapy for NSCLC

Authors: T. Chu, L. Jiang, W. Ying, B. Han

Published in: Clinical and Translational Oncology | Issue 3/2017

Abstract

Purpose

Paclitaxel is an effective treatment for some of the non-small-cell lung cancer (NSCLC) patients. However, prediction of the outcome of paclitaxel treatment at the early stage of the chemotherapy is difficult. M30 and M65 are circulating fragments of cytokeratin 18 released during apoptosis or necrosis, respectively, and have been used as markers to evaluate chemotherapy in some cancers. Here, we aimed to examine M30 and M65 values for predicting the therapeutic outcome of paclitaxel treatment of NSCLC.

Methods

The serum levels of M30 and M65 before and after paclitaxel treatment in advance-stage NSCLC patients were analyzed, and compared to those in healthy controls. The importance of the M30 and M65 levels to the outcome of chemotherapy was analyzed.

Result

We found that the serum M30 and M65 levels were higher in patients with NSCLC (n = 44) than in control healthy subjects (n = 56) (p < 0.001). Two days after paclitaxel treatment, the serum levels of both M30 and M65 significantly increased in NSCLC patients (p < 0.001). Neither marker alone significantly correlated with overall patient survival, but the ratio of M30 vs M65 appeared to be an important prognostic factor for the overall survival of the patients (p < 0.01).

Conclusion

Our results suggest that the serum M30/M65 ratio may be a prognostic factor for the outcome of paclitaxel treatment in NSCLC.

Caramori G, Casolari P, Cavallesco GN, Giuffre S, Adcock I, Papi A. Mechanisms involved in lung cancer development in COPD. Int J Biochem Cell Biol. 2011;43(7):1030–44. doi:10.1016/j.biocel.2010.08.022.CrossRefPubMed

Buttery RC, Rintoul RC, Sethi T. Small cell lung cancer: the importance of the extracellular matrix. Int J Biochem Cell Biol. 2004;36(7):1154–60. doi:10.1016/S1357-2725(03)00261-9.CrossRefPubMed

Pei J, Lou Y, Zhong R, Han B. MMP9 activation triggered by epidermal growth factor induced FoxO1 nuclear exclusion in non-small cell lung cancer. Tumour Biol. 2014;35(7):6673–8. doi:10.1007/s13277-014-1850-z.CrossRefPubMed

Weaver BA. How taxol/paclitaxel kills cancer cells. Mol Biol Cell. 2014;25(18):2677–81. doi:10.1091/mbc.E14-04-0916.CrossRefPubMedPubMedCentral

Meng J, Guo F, Xu H, Liang W, Wang C, Yang XD. Combination therapy using co-encapsulated resveratrol and paclitaxel in liposomes for drug resistance reversal in breast cancer cells in vivo. Sci Rep. 2016;6:22390. doi:10.1038/srep22390.CrossRefPubMedPubMedCentral

Zhu X, Guo J, He C, Geng H, Yu G, Li J, et al. Ultrasound triggered image-guided drug delivery to inhibit vascular reconstruction via paclitaxel-loaded microbubbles. Sci Rep. 2016;6:21683. doi:10.1038/srep21683.CrossRefPubMedPubMedCentral

Zhong ZF, Tan W, Wang SP, Qiang WA, Wang YT. Anti-proliferative activity and cell cycle arrest induced by evodiamine on paclitaxel-sensitive and -resistant human ovarian cancer cells. Sci Rep. 2015;5:16415. doi:10.1038/srep16415.CrossRefPubMedPubMedCentral

Ueno T, Toi M, Linder S. Detection of epithelial cell death in the body by cytokeratin 18 measurement. Biomed Pharmacother. 2005;59(Suppl 2):S359–62.CrossRefPubMed

Oyama K, Fushida S, Kinoshita J, Okamoto K, Makino I, Nakamura K, et al. Serum cytokeratin 18 as a biomarker for gastric cancer. Clin Exp Med. 2013;13(4):289–95. doi:10.1007/s10238-012-0202-9.CrossRefPubMed

10.

Dive C, Smith RA, Garner E, Ward T, George-Smith SS, Campbell F, et al. Considerations for the use of plasma cytokeratin 18 as a biomarker in pancreatic cancer. Br J Cancer. 2010;102(3):577–82. doi:10.1038/sj.bjc.6605494.CrossRefPubMedPubMedCentral

11.

Ausch C, Buxhofer-Ausch V, Olszewski U, Schiessel R, Ogris E, Hinterberger W, et al. Circulating cytokeratin 18 fragment m65-a potential marker of malignancy in colorectal cancer patients. J Gastrointest Surg. 2009;13(11):2020–6. doi:10.1007/s11605-009-0992-6.CrossRefPubMed

12.

Ausch C, Buxhofer-Ausch V, Olszewski U, Hinterberger W, Ogris E, Schiessel R, et al. Caspase-cleaved cytokeratin 18 fragment (M30) as marker of postoperative residual tumor load in colon cancer patients. Eur J Surg Oncol. 2009;35(11):1164–8. doi:10.1016/j.ejso.2009.02.007.CrossRefPubMed

13.

Sen F, Yildiz I, Odabas H, Tambas M, Kilic L, Karadeniz A, et al. Diagnostic value of serum M30 and M65 in patients with nasopharyngeal carcinoma. Tumour Biol. 2015;36(2):1039–44. doi:10.1007/s13277-014-2708-0.CrossRefPubMed

14.

Tas F, Karabulut S, Serilmez M, Yildiz I, Sen F, Ciftci R, et al. Clinical significance of serum M30 and M65 levels in melanoma. Melanoma Res. 2013;23(5):390–5. doi:10.1097/CMR.0b013e328363e4ab.CrossRefPubMed

15.

Tas F, Karabulut S, Bilgin E, Sen F, Yildiz I, Tastekin D, et al. Clinical significance of serum M30 and M65 levels in metastatic pancreatic adenocarcinoma. Tumour Biol. 2013;34(6):3529–36. doi:10.1007/s13277-013-0931-8.CrossRefPubMed

16.

Oven-Ustaalioglu B, Bilici A, Ercan S, Orcun A, Seker M, Ozkan A, et al. Serum M30 and M65 values in patients with advanced stage non-small-cell lung cancer compared with controls. Clin Transl Oncol. 2012;14(5):356–61. doi:10.1007/s12094-012-0808-0.CrossRefPubMed

17.

Ustaalioglu BB, Bilici A, Ercan S, Seker M, Orcun A, Gumus M. The prognostic importance of changing serum M30 and M65 values after chemotherapy in patients with advanced-stage non-small-cell lung cancer. Med Oncol. 2013;30(2):551. doi:10.1007/s12032-013-0551-6.CrossRefPubMed

18.

Kramer G, Erdal H, Mertens HJ, Nap M, Mauermann J, Steiner G, et al. Differentiation between cell death modes using measurements of different soluble forms of extracellular cytokeratin 18. Cancer Res. 2004;64(5):1751–6.CrossRefPubMed

Title: M30/M65 ratio predicts the outcome of paclitaxel chemotherapy for NSCLC
Authors: T. Chu
L. Jiang
W. Ying
B. Han
Publication date: 01-03-2017
Publisher: Springer International Publishing
Published in: Clinical and Translational Oncology / Issue 3/2017
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI: https://doi.org/10.1007/s12094-016-1533-x

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

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Result

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2017

European edition of the NCCN clinical practice guidelines: relevance of the translation and adaptation into Spanish

Consensus on the management of advanced radioactive iodine-refractory differentiated thyroid cancer on behalf of the Spanish Society of Endocrinology Thyroid Cancer Working Group (GTSEEN) and Spanish Rare Cancer Working Group (GETHI)

Thanks to reviewers

Mid-term oncologic outcome of a novel approach for locally advanced colon cancer with neoadjuvant chemotherapy and surgery

Clinical behavior of solitary fibrous tumor: a retrospective review of 30 patients

Identification of clinical biomarkers for patients with advanced hepatocellular carcinoma receiving sorafenib

Keynote webinar | Spotlight on antibody–drug conjugates in cancer