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Predicting the pathologic response of locally advanced rectal cancer to neoadjuvant concurrent chemoradiation using enzyme-linked immunosorbent assays (ELISAs) for biomarkers

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Abstract

Purpose

To investigate the role of biomarkers including serum tissue inhibitor of metalloproteinases-1 (TIMP-1), urokinase plasminogen activator receptor, vascular endothelial growth factor, and epidermal growth factor receptor in predicting pathologic response to neoadjuvant chemoradiation (NACRT) for rectal cancer.

Methods

Between 2007 and 2009, 50 clinical TNM stage II or III patients were analyzed in this prospective study. Pre- and post-NACRT serum levels of biomarkers were assessed using ELISAs. The primary and secondary endpoints were pathologic complete response (pCR) and Mandard regression grade (MRG).

Results

The pCR was reported in 5 patients (10.0 %). According to the MRG, fifteen patients (30.0 %) were divided into group A (Grade I–II), the others in group B (Grade III–V). On univariate analysis, post-NACRT TIMP-1 showed notable significance with pCR (P = 0.092) and significant correlation with MRG group A (P = 0.003). Post-NACRT TIMP-1 ≤ 204.5 ng/mL as cut-off value by ROC curve was associated with more pCR and MRG group A patients (P = 0.016 and 0.002). Interval between NACRT and surgery was related to pCR with approached trend levels of significance (P = 0.05) and to MRG group A significantly on univariate analysis of clinical factors (P = 0.031). On multivariate analysis, post-NACRT TIMP-1 was not significantly related to pCR (P = 0.187), while it was significantly associated with MRG (P = 0.009). Among clinical responders, post-NACRT TIMP-1 level ≤ 204.5 ng/mL was significantly associated with pCR (P = 0.021) and MRG group A (P = 0.003).

Conclusions

Post-NACRT serum TIMP-1 could be used as a predictive marker of pathologic response to NACRT in rectal cancer, even in patients with clinical response.

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Acknowledgments

This study was supported by a faculty research grant of Yonsei University College of Medicine for 2007 (6-2007-0192). The sponsor had no involvement in this manuscript.

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea

    Hong In Yoon, Woong Sub Koom, Yong Bae Kim & Ki Chang Keum

  2. Department of Surgery, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea

    Byung Soh Min, Kang Young Lee & Nam Kyu Kim

  3. Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea

    Sang Joon Shin & Joong Bae Ahn

  4. Department of Pharmacology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea

    Hong In Yoon

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Correspondence to Ki Chang Keum.

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Yoon, H.I., Koom, W.S., Kim, Y.B. et al. Predicting the pathologic response of locally advanced rectal cancer to neoadjuvant concurrent chemoradiation using enzyme-linked immunosorbent assays (ELISAs) for biomarkers. J Cancer Res Clin Oncol 140, 399–409 (2014). https://doi.org/10.1007/s00432-013-1578-y

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