. 2015 Oct 24:15:794.

doi: 10.1186/s12885-015-1783-y.

Prognostic significance of Traf2- and Nck- interacting kinase (TNIK) in colorectal cancer

Affiliations

¹ Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. htsrg2@tmd.ac.jp.
² Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. ishi.srg2@tmd.ac.jp.
³ Department of Translational Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan. ishiguro.srg2@tmd.ac.jp.
⁴ Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. okazaki3332@gmail.com.
⁵ Department of Systems Biology, Graduate School of Biochemical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan. kmogushi@juntendo.ac.jp.
⁶ Center for Minimally Invasive Surgery, Division of Colorectal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. h-kobayashi.srg2@tmd.ac.jp.
⁷ Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. s-iida@ohta-hp.or.jp.
⁸ Center for Public Health Informatics, National Institute of Public Health, 2-3-6 Minami, Wako-shi, Saitama, 351-0197, Japan. hmizushi@niph.go.jp.
⁹ Department of Systems Biology, Graduate School of Biochemical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan. tanaka@cim.tmd.ac.jp.
¹⁰ Department of Translational Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan. h-uetake.srg2@tmd.ac.jp.
¹¹ Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. sugi.srg2@gmail.com.

PMID: 26499327
PMCID: PMC4619995
DOI: 10.1186/s12885-015-1783-y

Prognostic significance of Traf2- and Nck- interacting kinase (TNIK) in colorectal cancer

Hidenori Takahashi et al. BMC Cancer. 2015.

. 2015 Oct 24:15:794.

doi: 10.1186/s12885-015-1783-y.

Authors

Affiliations

¹ Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. htsrg2@tmd.ac.jp.
² Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. ishi.srg2@tmd.ac.jp.
³ Department of Translational Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan. ishiguro.srg2@tmd.ac.jp.
⁴ Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. okazaki3332@gmail.com.
⁵ Department of Systems Biology, Graduate School of Biochemical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan. kmogushi@juntendo.ac.jp.
⁶ Center for Minimally Invasive Surgery, Division of Colorectal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. h-kobayashi.srg2@tmd.ac.jp.
⁷ Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. s-iida@ohta-hp.or.jp.
⁸ Center for Public Health Informatics, National Institute of Public Health, 2-3-6 Minami, Wako-shi, Saitama, 351-0197, Japan. hmizushi@niph.go.jp.
⁹ Department of Systems Biology, Graduate School of Biochemical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan. tanaka@cim.tmd.ac.jp.
¹⁰ Department of Translational Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan. h-uetake.srg2@tmd.ac.jp.
¹¹ Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. sugi.srg2@gmail.com.

PMID: 26499327
PMCID: PMC4619995
DOI: 10.1186/s12885-015-1783-y

Abstract

Background: The potential of expression profiling using microarray analysis as a tool to predict the prognosis for different types of cancer has been realized. This study aimed to identify a novel biomarker for colorectal cancer (CRC).

Methods: The expression profiles of cancer cells in 152 patients with stage I-III CRC were examined using microarray analysis. High expression in CRC cells, especially in patients with distant recurrences, was a prerequisite to select candidate genes. Thus, we identified seventeen candidate genes, and selected Traf2- and Nck-interacting kinase (TNIK), which was known to be associated with progression in CRC through Wnt signaling pathways. We analyzed the protein expression of TNIK using immunohistochemistry (IHC) and investigated the relationship between protein expression and patient characteristics in 220 stage I-III CRC patients.

Results: Relapse-free survival was significantly worse in the TNIK high expression group than in the TNIK low expression group in stage II (p = 0.028) and stage III (p = 0.006) patients. In multivariate analysis, high TNIK expression was identified as a significant independent risk factor of distant recurrence in stage III patients.

Conclusion: This study is the first to demonstrate the prognostic significance of intratumoral TNIK protein expression in clinical tissue samples of CRC, in that high expression of TNIK protein in primary tumors was associated with distant recurrence in stage II and III CRC patients. This TNIK IHC study might contribute to practical decision-making in the treatment of these patients.

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Figures

**Fig. 1**
TNIK immunostaining in representative CRC and normal colorectal epithelium. a Examining the entire tumor cross-section revealed that TNIK staining was heterogeneous. b (a) 0 no staining; (b) 1+ weak staining; (c) 2+ moderate staining; (d) 3+ strong staining; (e) normal epithelium staining

**Fig. 2**
a RFS and (b) OS curves of 220 stage I-III CRC patients stratified by TNIK expression

**Fig. 3**
RFS curves stratified by TNM-7^th stage and TNIK expression

See this image and copyright information in PMC

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Prognostic significance of Traf2- and Nck- interacting kinase (TNIK) in colorectal cancer

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Prognostic significance of Traf2- and Nck- interacting kinase (TNIK) in colorectal cancer

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