Prognostic and clinical significance of subcellular CDC27 for patients with rectal adenocarcinoma treated with adjuvant chemotherapy

Chang,Chia-Lin; Huang,Kevin Chih-Yang; Chen,Tsung-Wei; Chen,William Tzu-Liang; Huang,Hsuan-Hua; Liu,Ya-Ling; Kuo,Chia-Hui; Chao,K.S. Clifford; Ke,Tao-Wei; Chiang,Shu-Fen

doi:10.3892/ol.2022.13358

Prognostic and clinical significance of subcellular CDC27 for patients with rectal adenocarcinoma treated with adjuvant chemotherapy

Authors:
- Chia-Lin Chang
- Kevin Chih-Yang Huang
- Tsung-Wei Chen
- William Tzu-Liang Chen
- Hsuan-Hua Huang
- Ya-Ling Liu
- Chia-Hui Kuo
- K.S. Clifford Chao
- Tao-Wei Ke
- Shu-Fen Chiang
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Affiliations: Department of Hematology and Oncology, Ministry of Health and Welfare Feng Yuan Hospital, Taichung 42055, Taiwan, R.O.C., Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 40402, Taiwan, R.O.C., Graduate Institute of Biomedical Science, China Medical University, Taichung 40402, Taiwan, R.O.C., Department of Colorectal Surgery, Hsinchu China Medical University Hospital, Hsinchu 30272, Taiwan, R.O.C., Department of Pathology, Ministry of Health and Welfare Feng Yuan Hospital, Taichung 42055, Taiwan, R.O.C., Laboratory of Precision Medicine, Ministry of Health and Welfare Feng Yuan Hospital, Taichung 42055, Taiwan, R.O.C., Department of Colorectal Surgery, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan, R.O.C.
Published online on: May 31, 2022 https://doi.org/10.3892/ol.2022.13358
Article Number: 238
Copyright: © Chang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Rectal adenocarcinoma (READ) constitutes one‑third of newly diagnosed colorectal cancer cases. Surgery, chemotherapy and concurrent chemoradiotherapy are the main treatments to improve patient outcomes for READ. However, patients with READ receiving these treatments eventually relapse, leading to a poor survival outcome. The present study collected surgical specimens from patients with READ and determined that cytoplasmic cell division cycle 27 (CDC27) expression was associated with the risk of lymph node metastasis and distant metastasis. Nuclear CDC27 expression was negatively associated with 5‑year disease‑free survival (DFS) and 5‑year overall survival (OS) rates. Multivariate Cox proportional regression analysis showed that nuclear CDC27 was an independent prognostic factor in the patients with READ, especially in those treated with adjuvant chemotherapy. High nuclear CDC27 expression was significantly associated with poorer 5‑year DFS (HR, 2.106; 95% CI, 1.275‑3.570; P=0.003) and 5‑year OS (HR, 2.369; 95% CI, 1.270‑4.6810; P=0.005) rates. The data indicated that cytoplasmic CDC27 expression could affect tumor progression and that it plays an important role in metastasis. Nuclear CDC27 expression was markedly associated with poorer survival outcomes and was an independent prognostic factor in patients with postoperative adjuvant chemotherapy‑treated READ. Thus, CDC27 expression serves as a potential prognostic marker for rectal tumor progression and chemotherapy treatment.

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1	Wilkinson N: Management of rectal cancer. Surg Clin North Am. 100:615–628. 2020. View Article : Google Scholar : PubMed/NCBI
2	Heald RJ, Moran BJ, Ryall RD, Sexton R and MacFarlane JK: Rectal cancer: The Basingstoke experience of total mesorectal excision, 1978–1997. Arch Surg. 133:894–899. 1988.
3	Petersen SH, Harling H, Kirkeby LT, Wille-Jørgensen P and Mocellin S: Postoperative adjuvant chemotherapy in rectal cancer operated for cure. Cochrane Database Syst Rev. Mar 14–2012.(Epub ahead of print). View Article : Google Scholar
4	Stewart CL, Warner S, Ito K, Raoof M, Wu GX, Kessler J, Kim JY and Fong Y: Cytoreduction for colorectal metastases: Liver, lung, peritoneum, lymph nodes, bone, brain. When does it palliate, prolong survival, and potentially cure? Curr Probl Surg. 55:330–379. 2018.
5	Zhou Z, He M, Shah AA and Wan Y: Insights into APC/C: From cellular function to diseases and therapeutics. Cell Div. 11:92016. View Article : Google Scholar : PubMed/NCBI
6	Kazemi-Sefat GE, Keramatipour M, Talebi S, Kavousi K, Sajed R, Kazemi-Sefat NA and Mousavizadeh K: The importance of CDC27 in cancer: Molecular pathology and clinical aspects. Cancer Cell Int. 21:1602021. View Article : Google Scholar
7	Lee J, Moon B, Lee DH, Lee G and Park D: Identification of a novel protein interaction between Elmo1 and Cdc27. Biochem Biophys Res Commun. 471:497–502. 2016. View Article : Google Scholar : PubMed/NCBI
8	Link LA, Howley BV, Hussey GS and Howe PH: PCBP1/HNRNP E1 protects chromosomal integrity by translational regulation of CDC27. Mol Cancer Res. 14:634–646. 2016. View Article : Google Scholar : PubMed/NCBI
9	Qiu L, Tan X, Lin J, Liu RY, Chen S, Geng R, Wu J and Huang W: CDC27 induces metastasis and invasion in colorectal cancer via the promotion of epithelial-to-mesenchymal transition. J Cancer. 8:2626–2635. 2017. View Article : Google Scholar : PubMed/NCBI
10	Qiu L, Wu J, Pan C, Tan X, Lin J, Liu R, Chen S, Geng R and Huang W: Downregulation of CDC27 inhibits the proliferation of colorectal cancer cells via the accumulation of p21Cip1/Waf1. Cell Death Dis. 7:e20742016. View Article : Google Scholar : PubMed/NCBI
11	Song Y, Song W, Li Z, Song W, Wen Y, Li J, Xia Q and Zhang M: Corrigendum: CDC27 promotes tumor progression and affects PD-L1 expression in T-cell lymphoblastic lymphoma. Front Oncol. 10:5836982020. View Article : Google Scholar
12	Rajkumar T, Gopal G, Selvaluxmi G and Rajalekshmy KR: CDC27 protein is involved in radiation response in squamous cell cervix carcinoma. Indian J Biochem Biophys. 42:271–278. 2005.
13	Talvinen K, Karra H, Pitkänen R, Ahonen I, Nykänen M, Lintunen M, Söderström M, Kuopio T and Kronqvist P: Low cdc27 and high securin expression predict short survival for breast cancer patients. APMIS. 121:945–953. 2013. View Article : Google Scholar
14	Wang C, Su Z, Hou H, Li D, Pan Z, Tian W and Mo C: Inhibition of anaphase-promoting complex by silence APC/C(Cdh1) to enhance radiosensitivity of nasopharyngeal carcinoma cells. J Cell Biochem. 118:3150–3157. 2017. View Article : Google Scholar : PubMed/NCBI
15	Sansregret L, Patterson JO, Dewhurst S, López-García C, Koch A, McGranahan N, Chao WCH, Barry DJ, Rowan A, Instrell R, et al: APC/C dysfunction limits excessive cancer chromosomal instability. Cancer Discov. 7:218–233. 2017. View Article : Google Scholar : PubMed/NCBI
16	Malka D, Lièvre A, André T, Taïeb J, Ducreux M and Bibeau F: Immune scores in colorectal cancer: Where are we? Eur J Cancer. 140:105–118. 2020. View Article : Google Scholar
17	Chen TW, Huang KC, Chiang SF, Chen WT, Ke TW and Chao KSC: Prognostic relevance of programmed cell death-ligand 1 expression and CD8⁺ TILs in rectal cancer patients before and after neoadjuvant chemoradiotherapy. J Cancer Res Clin Oncol. 145:1043–1053. 2019. View Article : Google Scholar
18	Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL and Trotti A: AJCC Cancer Staging Manual. (7th edition). Springer; New York, NY: 2010
19	Chiang SF, Huang CY, Ke TW, Chen TW, Lan YC, You YS, Chen WT and Chao KSC: Upregulation of tumor PD-L1 by neoadjuvant chemoradiotherapy (neoCRT) confers improved survival in patients with lymph node metastasis of locally advanced rectal cancers. Cancer Immunol Immunother. 68:283–296. 2019. View Article : Google Scholar : PubMed/NCBI
20	Detre S, Saclani Jotti G and Dowsett M: A ‘quickscore’ method for immunohistochemical semiquantitation: Validation for oestrogen receptor in breast carcinomas. J Clin Pathol. 48:876–878. 1995. View Article : Google Scholar
21	Li T, Fu J, Zeng Z, Cohen D, Li J, Chen Q, Li B and Liu XS: TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 48:W509–W514. 2020. View Article : Google Scholar : PubMed/NCBI
22	Xin Y, Ning S, Zhang L and Cui M: CDC27 facilitates gastric cancer cell proliferation, invasion and metastasis via twist-induced epithelial-mesenchymal transition. Cell Physiol Biochem. 50:501–511. 2018. View Article : Google Scholar : PubMed/NCBI
23	Huang JY, Morley G, Li D and Whitaker M: Cdk1 phosphorylation sites on Cdc27 are required for correct chromosomal localisation and APC/C function in syncytial Drosophila embryos. J Cell Sci. 120:1990–1997. 2007. View Article : Google Scholar
24	Huang JY and Raff JW: The dynamic localisation of the Drosophila APC/C: Evidence for the existence of multiple complexes that perform distinct functions and are differentially localised. J Cell Sci. 115:2847–2856. 2002. View Article : Google Scholar
25	São Julião GP, Habr-Gama A, Vailati BB, Araujo SE, Fernandez LM and Perez RO: New strategies in rectal cancer. Surg Clin North Am. 97:587–604. 2017. View Article : Google Scholar
26	Liu Z, Meng X, Zhang H, Li Z, Liu J, Sun K, Meng Y, Dai W, Xie P, Ding Y, et al: Predicting distant metastasis and chemotherapy benefit in locally advanced rectal cancer. Nat Commun. 11:4308–4318. 2020. View Article : Google Scholar : PubMed/NCBI
27	Galluzzi L, Vitale I, Michels J, Brenner C, Szabadkai G, Harel-Bellan A, Castedo M and Kroemer G: Systems biology of cisplatin resistance: Past, present and future. Cell Death Dis. 5:e12572014. View Article : Google Scholar
28	Köberle B and Schoch S: Platinum complexes in colorectal cancer and other solid tumors. Cancers (Basel). 13:20732021. View Article : Google Scholar
29	Vodenkova S, Buchler T, Cervena K, Veskrnova V, Vodicka P and Vymetalkova V: 5-fluorouracil and other fluoropyrimidines in colorectal cancer: Past, present and future. Pharmacol Ther. 206:1074472020. View Article : Google Scholar : PubMed/NCBI
30	Bassermann F, Frescas D, Guardavaccaro D, Busino L, Peschiaroli A and Pagano M: The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response checkpoint. Cell. 134:256–267. 2008. View Article : Google Scholar
31	Hu K, Liao D, Wu W, Han AJ, Shi HJ, Wang F, Wang X, Zhong L, Duan T, Wu Y, et al: Targeting the anaphase-promoting complex/cyclosome (APC/C)-bromodomain containing 7 (BRD7) pathway for human osteosarcoma. Oncotarget. 5:3088–3100. 2014. View Article : Google Scholar
32	Giovinazzi S, Bellapu D, Morozov VM and Ishov AM: Targeting mitotic exit with hyperthermia or APC/C inhibition to increase paclitaxel efficacy. Cell Cycle. 12:2598–2607. 2013. View Article : Google Scholar : PubMed/NCBI
33	Wang J, Zhou F, Li Y, Li Q, Wu Z, Yu L, Yuan F, Liu J, Tian Y, Cao Y, et al: Cdc20 overexpression is involved in temozolomide-resistant glioma cells with epithelial-mesenchymal transition. Cell Cycle. 16:2355–2365. 2017. View Article : Google Scholar : PubMed/NCBI
34	Wu F, Lin Y, Cui P, Li H, Zhang L, Sun Z, Huang S, Li S, Huang S, Zhao Q and Liu Q: Cdc20/p55 mediates the resistance to docetaxel in castration-resistant prostate cancer in a Bim-dependent manner. Cancer Chemother Pharmacol. 81:999–1006. 2018. View Article : Google Scholar
35	Zhang S, Shen Y, Li H, Bi C and Sun Y, Xiong X, Wei W and Sun Y: The negative cross-talk between SAG/RBX2/ROC2 and APC/C E3 ligases in regulation of cell cycle progression and drug resistance. Cell Rep. 32:1081022020. View Article : Google Scholar : PubMed/NCBI
36	Lee SJ and Langhans SA: Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis. BMC Cancer. 12:442012. View Article : Google Scholar : PubMed/NCBI
37	Ren YQ, Fu F and Han J: MiR-27a modulates radiosensitivity of triple-negative breast cancer (TNBC) cells by targeting CDC27. Med Sci Monit. 21:1297–1303. 2015. View Article : Google Scholar
38	Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, Tosolini M, Camus M, Berger A, Wind P, et al: Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 313:1960–1964. 2006. View Article : Google Scholar