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  Identification of Predictive Markers for Response to Neoadjuvant Chemoradiation in Rectal Carcinomas by Proteomic Isotope Coded Protein Label (ICPL) Analysis

Croner, R. S., Sevim, M., Metodiev, M. V., Jo, P., Ghadimi, M., Schellerer, V., et al. (2016). Identification of Predictive Markers for Response to Neoadjuvant Chemoradiation in Rectal Carcinomas by Proteomic Isotope Coded Protein Label (ICPL) Analysis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 17(2): 209. doi:10.3390/ijms17020209.

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 Creators:
Croner, Roland S.1, Author
Sevim, Müzeyyen2, Author              
Metodiev, Metodi V.1, Author
Jo, Peter1, Author
Ghadimi, Michael1, Author
Schellerer, Vera1, Author
Brunner, Maximillian1, Author
Geppert, Carol1, Author
Rau, Tilman1, Author
Stuerzl, Michael1, Author
Naschberger, Elisabeth1, Author
Matzel, Klaus E.1, Author
Hohenberger, Werner1, Author
Lottspeich, Friedrich2, Author              
Kellermann, Josef2, Author              
Affiliations:
1external, ou_persistent22              
2Lottspeich, Friedrich / Protein Analysis, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565158              

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Free keywords: POSTOPERATIVE CHEMORADIOTHERAPY; CANCER; RADIOCHEMOTHERAPY; TRIAL; CAO/ARO/AIO-94; ADJUVANTrectal cancer; chemoradiation; proteomic; ICPL;
 Abstract: Neoadjuvant chemoradiation (nCRT) is an established procedure in stage union internationale contre le cancer (UICC) II/III rectal carcinomas. Around 53% of the tumours present with good tumor regression after nCRT, and 8%-15% are complete responders. Reliable selection markers would allow the identification of poor or non-responders prior to therapy. Tumor biopsies were harvested from 20 patients with rectal carcinomas, and stored in liquid nitrogen prior to therapy after obtaining patients' informed consent (Erlangen-No.3784). Patients received standardized nCRT with 5-Fluoruracil (nCRT I) or 5-Fluoruracil +/- Oxaliplatin (nCRT II) according to the CAO/ARO/AIO-04 protocol. After surgery, regression grading (Dworak) of the tumors was performed during histopathological examination of the specimens. Tumors were classified as poor (Dworak 1 + 2) or good (Dworak 3 + 4) responders. Laser capture microdissection (LCM) for tumor enrichment was performed on preoperative biopsies. Differences in expressed proteins between poor and good responders to nCRT I and II were identified by proteomic analysis (Isotope Coded Protein Label, ICPL) and selected markers were validated by immunohistochemistry. Tumors of 10 patients were classified as histopathologically poor (Dworak 1 or 2) and the other 10 tumor samples as histopathologically good (Dworak 3 or 4) responders to nCRT after surgery. Sufficient material in good quality was harvested for ICPL analysis by LCM from all biopsies. We identified 140 differentially regulated proteins regarding the selection criteria and the response to nCRT. Fourteen of these proteins were synchronously up-regulated at least 1.5-fold after nCRT I or nCRT II (e.g., FLNB, TKT, PKM2, SERINB1, IGHG2). Thirty-five proteins showed a complete reciprocal regulation (up or down) after nCRT I or nCRT II and the rest was regulated either according to nCRT I or II. The protein expression of regulated proteins such as PLEC1, TKT, HADHA and TAGLN was validated successfully by immunohistochemistry. ICPL is a valid method to identify differentially expressed proteins in rectal carcinoma tissue between poor vs. good responders to nCRT. The identified protein markers may act as selection criteria for nCRT in the future, but our preliminary findings must be reproduced and validated in a prospective cohort.

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Language(s): eng - English
 Dates: 2016
 Publication Status: Published online
 Pages: 16
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000371830800079
DOI: 10.3390/ijms17020209
 Degree: -

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Title: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Source Genre: Journal
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Publ. Info: POSTFACH, CH-4005 BASEL, SWITZERLAND : MDPI AG
Pages: - Volume / Issue: 17 (2) Sequence Number: 209 Start / End Page: - Identifier: ISSN: 1422-0067