MutT-related proteins are novel progression and prognostic markers for colorectal cancer
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Jin Li1, Cheng-Cheng Yang2, Xin-Yuan Tian1, Yun-Xuan Li2, Ju Cui3, Zhe Chen3, Zhou-Lu Deng4, Fu-Jun Chen5, Hiroshi Hayakawa6, Mutsuo Sekiguchi6 and Jian-Ping Cai1
1Peking University Fifth School of Clinical Medicine, Beijing Hospital, Beijing, P.R. China
2School of Pharmacy, Wenzhou Medical University, Wenzhou, P.R. China
3The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, P.R. China
4Department of General Surgery, China-Japan Friendship Hospital, Beijing, P.R. China
5Department of Anorectal Surgery, First Affiliated Hospital of Jiamusi University, Jiamusi, P.R. China
6Frontier Research Center, Fukuoka Dental College, Fukuoka, Japan
Jian-Ping Cai, email: [email protected]
Keywords: MutT-related proteins; oxidized nucleotides; colorectal cancer; clinical relevance; prognosis
Received: July 22, 2017 Accepted: August 17, 2017 Published: November 11, 2017
Background: MutT-related proteins, including MTH1, MTH2, MTH3 and NUDT5, can effectively degrade 8-oxoGua-containing nucleotides. The MTH1 expression is elevated in many types of human tumors and MTH1 overexpression correlates with the tumor pathological stage and poor prognosis. However, the expression of other MutT-related proteins in human cancers remains unknown. The present study systematically investigated the expression of MTH1, MTH2, MTH3 and NUDT5 in human colorectal cancer to establish its clinical significance.
Methods: Amounts of MutT-related mRNA and protein in CRC cell lines were assessed by qRT-PCR and Western blotting, respectively. Furthermore, the MutT-related protein expression was evaluated by immunohistochemical staining of tissue microarrays containing 87 paired CRC tissues and by Western blotting of 44 CRC tissue samples. Finally, the effect of knockdown of MutT-related proteins on CRC cell proliferation was investigated.
Results: The expression of MTH1, MTH2, MTH3 and NUDT5 was significantly higher in CRC cells and CRC tissues than normal cells and tissues, and this phenomenon was significantly associated with AJCC stage and lymph node metastasis of CRC specimens. CRC patients with high expression of MTH1, MTH2 or NUDT5 had an extremely poor overall survival after surgical resection. Notably, NUDT5 was an independent prognostic factor of CRC patients. We found that knockdown of MutT-related proteins inhibited CRC cell proliferation.
Conclusions: We showed for the first time that MutT-related proteins play an important role in CRC progression and prognosis. Further investigations are needed to elucidate the role of these proteins in CRC progression and their potential use for therapeutic targets.
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