Abstract 5016: Elevated serum monocyte chemotactic protein 4 (MCP4) as a novel noninvasive prognostic and predictive biomarker for detection of metastasis in colorectal cancer
Authors: Okugawa Yoshinaga , Toiyama Yuji , Tanaka Koji , Kawamura Mikio , Kitajima Takahito , Shimura Tadanobu , Imaoka Hiroki , Fujikawa Hiroyuki , Saigusa Susumu , Inoue Yasuhiro , Tanaka Motoyoshi , Mohri Yasuhiko , Miki Chikao , Goel Ajay , Kusunoki Masato 
Published: July 2016

Abstract
Purpose. Despite the recent progress in diagnosis and treatment for colorectal cancer (CRC), prognosis of CRC patients still remains poor. Metastatic recurrence is the major causes of cancer-related death in CRC patients, and recent progress in treatment options, especially technical advances in invasive treatment for metastatic lesion, have improved the prognosis of CRC patients with metastasis. Furthermore, almost half of patients that receive chemotherapy derive no clinical benefit, though all are exposed to these severe toxic and expensive therapeutic regimens in patients with metastatic CRC patients. In view of these underlying issues, for improvement of patient's prognosis, there is a keen interest in developing robust biomarkers that can identify the subset of patients who can benefit from intensive post-treatment surveillance protocols for early detection of recurrence, and prompt decision of appropriate treatment protocol. Herein, we systemically and comprehensively evaluated differentially levels of serum cytokines using array-based techniques to identify novel and reliable serum biomarker to predict metastasis and poor outcome in CRC.
Methods. The study design included an initial dual screening phases, and followed by a subsequent clinical validation phase in this study.In discovery phase, we examined cytokine profiling using preoperative serum from two different CRC cohorts (n = 30) to identify differentially expressed serum cytokines in CRC patients with metastasis. In validation phase, serum levels of MCP-4 were assessed in 194 CRC patients by enzyme-linked immunosorbent assay, and their relationships with clinicopathological findings, including recurrence and survival, were investigated.
Results. In discovery phase, three cytokines (elevated: MCP-4, ENA-78; decreased:Ckb8-1) were overlapped as a differentially expressed cytokines in serum from CRC patients with metastasis compared those without metastasis. High serum MCP-4 was significantly associated with older age (p = 0.033), advanced T stage (p = 0.029), distant metastasis (p = 0.011) and UICC stage classification (p = 0.006). Cox regression analysis showed that elevated MCP-4 was a significant and independent prognostic factor of disease free survival (HR:2.6, 95%CI:1.0-6.7) and overall survival (HR:2.7, 95%CI:1.3-5.9) in all CRC patients. Furthermore, logistic regression analysis revealed that high serum MCP-4 level was an independent marker in predicting distant metastasis in CRC (OR:3.8, 95%CI:1.3-10.9).
Conclusion. Our comprehensive study highlights the clinical feasibility of serum MCP-4 as a prognostic and predictive biomarker for distant metastasis and recurrence in CRC patients. Quantification of serum MCP-4 concentration might support the early detection/prediction of recurrence and may contribute to the prediction of clinical outcomes in CRC.
Citation Format: Yoshinaga Okugawa, Yuji Toiyama, Koji Tanaka, Mikio Kawamura, Takahito Kitajima, Tadanobu Shimura, Hiroki Imaoka, Hiroyuki Fujikawa, Susumu Saigusa, Yasuhiro Inoue, Motoyoshi Tanaka, Yasuhiko Mohri, Chikao Miki, Ajay Goel, Masato Kusunoki. Elevated serum monocyte chemotactic protein 4 (MCP4) as a novel noninvasive prognostic and predictive biomarker for detection of metastasis in colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5016.