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Serum LOX-1 is a novel prognostic biomarker of colorectal cancer

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Abstract

Background

Colorectal cancer is the third most common cancer worldwide. If biomarkers can be identified in liquid biopsy, diagnosis and treatment can be optimized even when cancerous tissues are not available. The purpose of this study was to identify proteins from liquid biopsy that would be useful as markers of poor prognosis.

Methods

First, we comprehensively analyzed serum proteins to identify potential biomarkers and focused on serum lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). The relationship between LOX-1 and the prognosis of patients with colorectal cancer has not been reported. Next, we validated this marker using serum samples from 238 patients with colorectal cancer by ELISA and 100 tissue samples by immunohistochemical staining.

Results

The optimal cut-off value of serum LOX-1 was 538.7 pg/mL according to time-dependent receiver operating characteristics curve analysis. The overall survival of patients with high levels of serum LOX-1 was significantly poorer than that of individuals with low levels of LOX-1 in the training and test datasets. In multivariate analysis for overall survival, serum LOX-1 was an independent prognostic factor identified in liquid biopsy (hazard ratio = 1.729, p = 0.027). The prognosis of patients with high LOX-1 expression in tumor tissues was significantly poorer than that of individuals with low expression (p =0.047 ). Additionally, inflammatory factors such as white blood cell count, C-reactive protein level, neutrophil/lymphocyte ratio, and monocyte/lymphocyte ratio were significantly higher in the group with high serum LOX-1 levels.

Conclusions

Serum LOX-1 might be a useful biomarker of poor prognosis in colorectal cancer.

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Acknowledgements

The authors thank Ms. Hiroko Takenouchi and Mr. Toshihiko Kobayashi for their excellent technical assistance with this work.

Funding

This study was performed as a research program of the Project for Development of Innovative Research on Cancer Therapeutics (P-DIRECT; 11039020) and The Japan Agency for Medical Research and Development (AMED; 15cm0106085h0005). This study was supported in part by a grant for Leading Advanced Projects for Medical Innovation (LEAP; 16am0001006h0003) from the Japan Agency for Medical Research and Development.

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Authors and Affiliations

  1. Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan

    Chiyo Nakashima-Nakasuga, Shoichi Hazama, Nobuaki Suzuki, Yuki Nakagami, Ming Xu, Shin Yoshida, Shinobu Tomochika, Nobuyuki Fujiwara, Satoshi Matsukuma, Hiroto Matsui, Yukio Tokumitsu, Shinsuke Kanekiyo, Yoshitaro Shindo, Noriko Maeda, Ryouichi Tsunedomi, Michihisa Iida, Shigeru Takeda & Hiroaki Nagano

  2. Department of Translational Research and Developmental Therapeutics against Cancer, Yamaguchi University School of Medicine, Ube, Japan

    Shoichi Hazama & Yuki Nakagami

  3. Oncology Center, Yamaguchi University Hospital, Ube, Japan

    Shigefumi Yoshino

  4. Department of Gastroenterological Surgery, Kawasaki Medical School, Kurashiki, Japan

    Tomio Ueno

  5. Division of Electrical, Electronic and Information Engineering, Graduate School of Sciences and Technology for Innovation, Yamaguchi University, Ube, Japan

    Yoshihiko Hamamoto & Hiroyuki Ogihara

  6. Department of Diagnostic Pathology, Yamaguchi University Hospital, Ube, Japan

    Yoshinobu Hoshii

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Correspondence to Hiroaki Nagano.

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10147_2020_1673_MOESM1_ESM.tif

Supplementary file1. Fig. S1. Time-dependent receiver operator characteristic (ROC) curve analysis to determine the best cut-off period. Thirty-five months was selected as the best cut-off period from the analysis and based on clinical perspectives. (TIF 638 kb)

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Nakashima-Nakasuga, C., Hazama, S., Suzuki, N. et al. Serum LOX-1 is a novel prognostic biomarker of colorectal cancer. Int J Clin Oncol 25, 1308–1317 (2020). https://doi.org/10.1007/s10147-020-01673-2

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