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


CONCLUSIONS
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.
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.
Hidenori
H
Takahashi
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.
Toshiaki
T
Ishikawa
Department of Translational Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan. ishiguro.srg2@tmd.ac.jp.
Megumi
M
Ishiguro
Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. okazaki3332@gmail.com.
Satoshi
S
Okazaki
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.
Kaoru
K
Mogushi
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.
Hirotoshi
H
Kobayashi
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.
Satoru
S
Iida
Center for Public Health Informatics, National Institute of Public Health, 2-3-6 Minami, Wako-shi, Saitama, 351-0197, Japan. hmizushi@niph.go.jp.
Hiroshi
H
Mizushima
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.
Hiroshi
H
Tanaka
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.
Hiroyuki
H
Uetake
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.
Kenichi
K
Sugihara
D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D000081410:Germinal Center Kinases; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000378:metabolism*; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D000081410:Germinal Center Kinases; D017346:Protein Serine-Threonine Kinases; C000631454:TNIK protein, human