Journal Article
. 2018 Oct; 7(11):.
doi: 10.3390/jcm7110390.

Circulating Levels of Osteopontin Predict Patients' Outcome after Resection of Colorectal Liver Metastases

Sven H Loosen 1 Daniel Heise 2 Cees H Dejong 3 Sanchari Roy 4 Frank Tacke 5 Christian Trautwein 6 Christoph Roderburg 7 Tom Luedde 8 Ulf P Neumann 9 Marcel Binnebösel 10 
Affiliations
  • PMID: 30373147
  •     32 References
  •     5 citations

Abstract

For colorectal liver metastases (CRLM), surgical resection is the only potentially curative therapy, but even successfully resected patients often face disease recurrence, leading to 5-year survival rate below 50%. Despite available preoperative stratification strategies, it is not fully elucidated which patients actually benefit from CRLM resection. Here we evaluated osteopontin, a secreted glyco-phosphoprotein, as a biomarker in the context of CRLM resection. Tissue levels of osteopontin were analysed in CRLM using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Pre- and postoperative osteopontin serum concentrations were analysed by enzyme-linked immunosorbent assay (ELISA) in 125 patients undergoing resection of CRLM as well as 65 healthy controls. Correlating with an upregulation of osteopontin tissue expression in CRLM, osteopontin serum levels were significantly elevated in patients with CRLM compared to healthy controls. Importantly, high pre- and post-operative osteopontin serum levels were associated with a poor prognosis after tumour resection. Patients with initial osteopontin serum levels above our ideal cut-off value of 264.4 ng/mL showed a significantly impaired median overall survival of 304 days compared to 1394 days for patients with low osteopontin levels. Together, our data suggest a role of osteopontin as a prognostic biomarker in patients with resectable CRLM that might help to identify patients who particularly benefit from liver resection.

Keywords: CEA; CRLM; OPN; biomarker; prognosis.

Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.
Jacques Ferlay, Isabelle Soerjomataram, +6 authors, Freddie Bray.
Int J Cancer, 2014 Sep 16; 136(5). PMID: 25220842
Highly Cited.
Osteopontin Promotes Cell Migration and Invasion, and Inhibits Apoptosis and Autophagy in Colorectal Cancer by activating the p38 MAPK Signaling Pathway.
Ren-Hong Huang, Ying-Jun Quan, +7 authors, Zhi-Jun Min.
Cell Physiol Biochem, 2017 Apr 05; 41(5). PMID: 28376477
Colorectal cancer statistics, 2017.
Rebecca L Siegel, Kimberly D Miller, +4 authors, Ahmedin Jemal.
CA Cancer J Clin, 2017 Mar 02; 67(3). PMID: 28248415
Highly Cited.
Surgical therapy of hepatic colorectal metastasis.
Y Fong.
CA Cancer J Clin, 2001 Feb 24; 49(4). PMID: 11198884
Review.
Osteopontin identified as lead marker of colon cancer progression, using pooled sample expression profiling.
Deepak Agrawal, Tingan Chen, +6 authors, Timothy J Yeatman.
J Natl Cancer Inst, 2002 Apr 04; 94(7). PMID: 11929952
Highly Cited.
OPN -Revisited.
Vijayanirmala Subraman, Muthukumar Thiyagarajan, N Malathi, Sharada T Rajan.
J Clin Diagn Res, 2015 Aug 13; 9(6). PMID: 26266236    Free PMC article.
Review.
FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study.
Chiara Cremolini, Fotios Loupakis, +17 authors, Alfredo Falcone.
Lancet Oncol, 2015 Sep 05; 16(13). PMID: 26338525
Highly Cited.
Functional characterization of stromal osteopontin in melanoma progression and metastasis.
Santosh Kumar, Priyanka Sharma, +3 authors, Gopal C Kundu.
PLoS One, 2013 Aug 13; 8(7). PMID: 23935934    Free PMC article.
Discrepancies between medical oncologists and surgeons in assessment of resectability and indication for chemotherapy in patients with colorectal liver metastases.
K Homayounfar, A Bleckmann, +6 authors, T Liersch.
Br J Surg, 2014 Apr 24; 101(5). PMID: 24756914
Immunohistochemical expression of osteopontin in gastric cancer.
Motohiro Imano, Takao Satou, +12 authors, Harumasa Ohyanagi.
J Gastrointest Surg, 2009 Jul 08; 13(9). PMID: 19582521
Osteopontin-enhanced hepatic metastasis of colorectal cancer cells.
Jianjin Huang, Chi Pan, +2 authors, Ling Ding.
PLoS One, 2012 Nov 01; 7(10). PMID: 23112867    Free PMC article.
Expression of osteopontin coregulators in primary colorectal cancer and associated liver metastases.
D J Mole, C O'Neill, +6 authors, F C Campbell.
Br J Cancer, 2011 Feb 24; 104(6). PMID: 21343932    Free PMC article.
The surgical treatment of hepatic metastases in colorectal carcinoma.
Ulf Peter Neumann, Daniel Seehofer, Peter Neuhaus.
Dtsch Arztebl Int, 2010 Jun 10; 107(19). PMID: 20532128    Free PMC article.
Review.
Circulating soluble urokinase plasminogen activator receptor is stably elevated during the first week of treatment in the intensive care unit and predicts mortality in critically ill patients.
Alexander Koch, Sebastian Voigt, +7 authors, Frank Tacke.
Crit Care, 2011 Feb 18; 15(1). PMID: 21324198    Free PMC article.
Highly Cited.
Resectability of colorectal liver metastases: an evolving definition.
Flavio G Rocha, W Scott Helton.
HPB (Oxford), 2012 Apr 11; 14(5). PMID: 22487064    Free PMC article.
Clinical significance of the upregulated osteopontin mRNA expression in human colorectal cancer.
Wang Likui, Wang Hong, Zhang Shuwen.
J Gastrointest Surg, 2009 Sep 19; 14(1). PMID: 19763701
Cetuximab plus FOLFIRINOX (ERBIRINOX) as first-line treatment for unresectable metastatic colorectal cancer: a phase II trial.
Eric Assenat, Francoise Desseigne, +9 authors, Marc Ychou.
Oncologist, 2011 Oct 22; 16(11). PMID: 22016477    Free PMC article.
Predictors of surgical non-referral for colorectal liver metastases.
Ali Ahmad, Jeffrey Reha, +2 authors, Steven C Katz.
J Surg Res, 2016 Sep 14; 205(1). PMID: 27621019
Cutoff Finder: a comprehensive and straightforward Web application enabling rapid biomarker cutoff optimization.
Jan Budczies, Frederick Klauschen, +4 authors, Carsten Denkert.
PLoS One, 2012 Dec 20; 7(12). PMID: 23251644    Free PMC article.
Highly Cited.
Serum OPN expression for identification of gastric cancer and atrophic gastritis and its influencing factors.
Tiejun Chen, Liping Sun, +3 authors, Yuan Yuan.
PLoS One, 2014 Dec 06; 9(12). PMID: 25479069    Free PMC article.
FOLFIRINOX bevacizumab is a promising therapy for chemorefractory metastatic colorectal cancer.
Marie Chaix, Julie Vincent, Véronique Lorgis, François Ghiringhelli.
Oncology, 2014 Jul 12; 87(3). PMID: 25012455
Management of potentially resectable colorectal cancer liver metastases.
Fausto Meriggi, Paola Bertocchi, Alberto Zaniboni.
World J Gastrointest Surg, 2013 May 28; 5(5). PMID: 23710291    Free PMC article.
The impact of osteopontin on prognosis and clinicopathology of colorectal cancer patients: a systematic meta-analysis.
Mingfei Zhao, Feng Liang, +2 authors, Jianmin Zhang.
Sci Rep, 2015 Aug 04; 5. PMID: 26234583    Free PMC article.
Elevated levels of circulating osteopontin are associated with a poor survival after resection of cholangiocarcinoma.
Sven H Loosen, Christoph Roderburg, +15 authors, Tom Luedde.
J Hepatol, 2017 Jul 03; 67(4). PMID: 28668580
Combination of haptoglobin and osteopontin could predict colorectal cancer hepatic metastasis.
Lichao Sun, Jian Pan, +5 authors, Yuliang Ran.
Ann Surg Oncol, 2012 Jan 06; 19(7). PMID: 22219064
Outcomes of extended versus limited indications for patients undergoing a liver resection for colorectal cancer liver metastases.
Ronald M van Dam, Toine M Lodewick, +7 authors, Cornelis H C Dejong.
HPB (Oxford), 2013 Nov 20; 16(6). PMID: 24246003    Free PMC article.
Colorectal Cancer Liver Metastasis: Evolving Paradigms and Future Directions.
Luai R Zarour, Sudarshan Anand, +15 authors, Skye C Mayo.
Cell Mol Gastroenterol Hepatol, 2017 Mar 10; 3(2). PMID: 28275683    Free PMC article.
Highly Cited. Review.
Resection of colorectal liver metastases.
J Scheele, R Stang, A Altendorf-Hofmann, M Paul.
World J Surg, 1995 Jan 01; 19(1). PMID: 7740812
Highly Cited.
Colorectal Liver Metastases: A Critical Review of State of the Art.
Robert P Jones, Norihiro Kokudo, +5 authors, Graeme J Poston.
Liver Cancer, 2016 Dec 21; 6(1). PMID: 27995090    Free PMC article.
Review.
Evaluation of osteopontin as biomarker for pancreatic adenocarcinoma.
Jens Koopmann, Neal S Fedarko, +6 authors, Michael Goggins.
Cancer Epidemiol Biomarkers Prev, 2004 Mar 10; 13(3). PMID: 15006928
Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases.
Eddie K Abdalla, Jean-Nicolas Vauthey, +5 authors, Steven A Curley.
Ann Surg, 2004 May 29; 239(6). PMID: 15166961    Free PMC article.
Highly Cited.
Pre- and post-translational regulation of osteopontin in cancer.
Pieter H Anborgh, Jennifer C Mutrie, Alan B Tuck, Ann F Chambers.
J Cell Commun Signal, 2011 Apr 26; 5(2). PMID: 21516514    Free PMC article.
Serum levels of bone sialoprotein correlate with portal pressure in patients with liver cirrhosis.
Fabian Benz, Andreas Bogen, +10 authors, Christoph Roderburg.
PLoS One, 2020 Apr 18; 15(4). PMID: 32302330    Free PMC article.
High baseline soluble urokinase plasminogen activator receptor (suPAR) serum levels indicate adverse outcome after resection of pancreatic adenocarcinoma.
Sven H Loosen, Frank Tacke, +13 authors, Tom Luedde.
Carcinogenesis, 2019 Feb 26; 40(8). PMID: 30805627    Free PMC article.
Impact of primary tumour location on colorectal liver metastases: A systematic review.
George Bingham, Alysha Shetye, Reena Suresh, Reza Mirnezami.
World J Clin Oncol, 2020 Jul 31; 11(5). PMID: 32728532    Free PMC article.
Prognostic Significance of Serum PD-L1 Level in Patients with Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma Treated with Combination Cytotoxic Chemotherapy.
Rong Fu, Chuan-Qing Jing, +2 authors, Hui-Jie Li.
Cancer Manag Res, 2021 Jul 01; 13. PMID: 34188546    Free PMC article.
Circulating Osteopontin Levels and Outcomes in Patients Hospitalized for COVID-19.
Salim S Hayek, Christoph Roderburg, +9 authors, Sven H Loosen.
J Clin Med, 2021 Sep 11; 10(17). PMID: 34501358    Free PMC article.