Abstract
Purpose
Colorectal liver metastases (CLM) have significant molecular heterogeneity, which contributes to the risk of recurrence following surgery. Most of the traditional scores intended to predict recurrence is based on clinicopathological variables and it is unclear whether incorporating molecular biomarkers might improve our assessment of the risk of recurrence. Our aim was to determine if molecular biomarkers might be associated with the risk of recurrence after surgery of CLM.
Patients and methods
A total of 121 patients diagnosed with colorectal cancer (CRC) with resected liver metastases were included. The role of several clinicopathological variables to predict patient’s outcome after resection of liver metastases was analyzed. Eighteen genes related to CRC pathogenesis were also included in the analyses. Univariate and multivariate stepwise Cox regression analyses were performed to identify factors associated with recurrence and the risk of death.
Results
Eight prognostic factors for progression-free survival and nine factors for overall survival were identified in the univariate analyses. After adjusting for other risk factors, only the expression of two molecular factors was associated with the risk of recurrence: TS (HR 0.631, 95 % CI 0.422–0.944) and SMAD4 (HR 1.680, 95 % CI 1.047–2.695). None of the variables was significantly associated with the risk of death in the multivariate analyses.
Conclusions
The prognostic significance of most traditional clinicopathological variables might be insufficient to define patients at risk for recurrence after liver metastases resection. Molecular biomarkers might improve the identification of patients with higher risk of recurrence.
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References
Choti MA, Sitzmann JV, Tiburi MF, Sumetchotimetha W, Rangsin R, Schulick RD, et al. Trends in long term survival following liver resection for hepatic colorectal metastases. Ann Surg. 2002;235:759–66.
Rees M, Tekkis PP, Welsh FKS, Welsh FK, O’Rourke T, John TG. Evaluation of long term survival after hepatic resection for metastatic colorectal cancer. A multifactorial model of 929 patients. Ann Surg. 2008;247:125–35.
Figueras J, Valls C, Rafecas A, Fabregat J, Ramos E, Jaurrieta E. Resection rate and effect of postoperative chemotherapy on survival after surgery for colorectal liver metastases. Br J Surg. 2001;88(7):980–5.
Weber SM, Jarnagin WR, DeMatteo RP, Blumgart LH, Fong Y. Survival after resection of multiple hepatic colorectal metastases. Ann Surg Oncol. 2000;7:643–50.
Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999;230:309–18.
Lise M, Bacchetti S, Da Pian P, Nitti D, Pilati P. Patterns of recurrence after resection of colorectal liver metastases: prediction by models of outcome analysis. World J Surg. 2001;25:638–44.
Malik HZ, Prasad R, Halazun KJ, Aldoori A, Al-Mukhtar A, Gomez D, et al. Preoperative prognostic score for predicting survival after hepatic resection for colorectal liver metastases. Ann Surg. 2007;246:806–14.
Markowitz SD, Bertagnolli MM. Molecular origins of cancer: molecular basis of colorectal cancer. N Engl J Med. 2009;361(25):2449–60. doi:10.1056/NEJMra0804588.
Mejia A, Schulz S, Hyslop T, Weinberg DS, Walkman SAJ. Molecular staging individualizing cancer management. Surg Oncol. 2012;105(5):468–74. doi:10.1002/jso.21858.
Choi HJ, Hyun MS, Jung GJ, Kim SS, Hong SH. Tumor angiogenesis as a prognostic predictor in colorectal carcinoma with special reference to mode of metastasis and recurrence. Oncology. 1998;55(6):575–81.
Tokunaga T, Nakamura M, Oshika Y, Abe Y, Ozeki Y, Fukushima Y, et al. Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer. Br J Cancer. 1999;79(2):354–9.
Belluco C, Guillem JG, Kemeny N, Huang Y, Klimstra D, Berger MF, et al. p53 nuclear protein overexpression in colorectal cancer: a dominant predictor of survival in patients with advanced hepatic metastases. J Clin Oncol. 1996;14(10):2696–701.
Dômont J, Pawlik TM, Boige V, Rose M, Weber JC, Hoff PM, et al. Catalytic subunit of human telomerase reverse transcriptase is an independent predictor of survival in patients undergoing curative resection of hepatic colorectal metastases: a multicenter analysis. J Clin Oncol. 2005;23(13):3086–93.
Petrowsky H, Sturm I, Graubitz O, Kooby DA, Staib-Sebler E, Gog C, et al. Relevance of Ki-67 antigen expression and K-ras mutation in colorectal liver metastases. EJSO. 2001;27(1):80–7.
Laird A, O’Mahony FC, Nanda J. Differential expression of prognostic proteomic markers in primary tumour, venous tumour thrombus and metastatic renal cell cancer tissue and correlation with patient outcome. PLoS One. 2013;8(4):e60483. doi:10.1371/journal.pone.0060483.
Gerlinger Marco, Rowan AJ. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. NEJM. 2012;366(10):883–92.
Boulay JL, Mild G, Lowy A, Reuter J. SMAD4 is a predictive marker for 5-fluorouracil-based chemotherapy in patients with colorectal cancer. Br J Cancer. 2002;87(6):630–4.
Yamane T, Seshimo A, Kameoka S. Analysis of the mRNA expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT) in liver metastases from colorectal cancer. Hepatogastroenterology. 2012;60(122):291–5.
Golfinopoulos V, Salanti G, Pavlidis N, Ioannidis JP. Survival and disease-progression benefits with treatment regimens for advanced colorectal cancer: a meta-analysis. Lancet Oncol. 2007;8(10):898–911.
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López-Gómez, M., Moreno-Rubio, J., Suárez-García, I. et al. SMAD4 and TS expression might predict the risk of recurrence after resection of colorectal liver metastases. Clin Transl Oncol 17, 133–138 (2015). https://doi.org/10.1007/s12094-014-1202-x
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DOI: https://doi.org/10.1007/s12094-014-1202-x