The combination of positive anti‑WDR1 antibodies with negative anti‑CFL1 antibodies in serum is a poor prognostic factor for patients with esophageal carcinoma

Ito,Masaaki; Yajima,Satoshi; Suzuki,Takashi; Oshima,Yoko; Nanami,Tatsuki; Sumazaki,Makoto; Shiratori,Fumiaki; Wang,Hao; Hu,Liubing; Takizawa,Hirotaka; Li,Shu-Yang; Iwadate,Yasuo; Hiwasa,Takaki; Shimada,Hideaki

doi:10.3892/mi.2023.71

The combination of positive anti‑WDR1 antibodies with negative anti‑CFL1 antibodies in serum is a poor prognostic factor for patients with esophageal carcinoma

Authors:
- Masaaki Ito
- Satoshi Yajima
- Takashi Suzuki
- Yoko Oshima
- Tatsuki Nanami
- Makoto Sumazaki
- Fumiaki Shiratori
- Hao Wang
- Liubing Hu
- Hirotaka Takizawa
- Shu-Yang Li
- Yasuo Iwadate
- Takaki Hiwasa
- Hideaki Shimada
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Affiliations: Department of Clinical Oncology, Toho University Graduate School of Medicine, Tokyo 143-8541, Japan, Department of Gastroenterological Surgery, Toho University School of Medicine, Tokyo 143-8541, Japan, Stroke Center, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China, Department of Anesthesiology, Stroke Center, The First Affiliated Hospital and Health Science Center, Jinan University, Guangzhou, Guangdong 510630, P.R. China, Port Square Kashiwado Clinic, Kashiwado Memorial Foundation, Chiba 260-0025, Japan, Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
Published online on: January 31, 2023 https://doi.org/10.3892/mi.2023.71
Article Number: 11
Copyright : © Ito et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

WD repeat‑containing protein 1 (WDR1) regulates the cofilin 1 (CFL1) activity, promotes cytoskeleton remodeling, and thus, facilitates cell migration and invasion. A previous study reported that autoantibodies against CFL1 and β‑actin were useful biomarkers for diagnosing and predicting the prognosis of patients with esophageal carcinoma. Therefore, the present study aimed to evaluate the serum levels of anti‑WDR1 antibodies (s‑WDR1‑Abs) combined with serum levels of anti‑CFL1 antibodies (s‑CFL1‑Abs) in patients with esophageal carcinoma. Serum samples obtained from 192 patients with esophageal carcinoma and other solid cancers. And s‑WDR1‑Ab and s‑CFL1‑Ab titers were analyzed using the amplified luminescent proximity homogeneous assay‑linked immunosorbent assay. Compared with those of healthy donors, the s‑WDR1‑Ab levels were significantly higher in the 192 patients with esophageal, whereas these were not significantly higher in the samples from patients with gastric, colorectal, lung, or breast cancer. In 91 patients treated with surgery, sex, tumor depth, lymph node metastasis, stage and C‑reactive protein levels were significantly associated with overall survival, as determined using the log‑rank test, whereas the squamous cell carcinoma antigen, p53 antibody and s‑WDR1‑Ab levels tended to be associated with a worse prognosis. Although no significant difference was observed in the survival between the positive and negative groups of s‑WDR1‑Abs or s‑CFL1‑Abs alone in the Kaplan‑Meier test, the patients in the s‑WDR1‑Ab‑positive and s‑CFL1‑Ab‑negative groups exhibited a significantly poorer prognosis in the overall survival analysis. On the whole, the present study demonstrates that the combination of positive anti‑WDR1 antibodies with negative anti‑CFL1 antibodies in serum may be a poor prognostic factor for patients with esophageal carcinoma.

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1	Suzuki T, Yajima S, Okamura A, Yoshida N, Taniyama Y, Murakami K, Ohkura Y, Nakajima Y, Yagi K, Fukuda T, et al: Prognostic impact of carcinoembryonic antigen in 1822 surgically treated esophageal squamous cell carcinoma: Multi-institutional study of the Japan Esophageal Society. Dis Esophagus. 35(doac029)2022.PubMed/NCBI View Article : Google Scholar
2	Sahin U, Tureci O, Schmitt H, Cochlovius B, Johannes T, Schmits R, Stenner F, Luo G, Schobert I and Pfreundschuhet M: Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci USA. 92:11810–11813. 1995.PubMed/NCBI View Article : Google Scholar
3	Nakashima K, Shimada H, Ochiai T, Kuboshima M, Kuroiwa N, Okazumi S, Matsubara H, Nomura F, Takiguchi M and Hiwasa T: Serological identification of TROP2 by recombinant cDNA expression cloning using sera of patients with esophageal squamous cell carcinoma. Int J Cancer. 112:1029–1035. 2004.PubMed/NCBI View Article : Google Scholar
4	Kuboshima M, Shimada H, Liu TL, Nakashima K, Nomura F, Takiguchi M, Hiwasa T and Ochiai T: Identification of a novel SEREX antigen, SLC2A1/GLUT1, in esophageal squamous cell carcinoma. Int J Oncol. 28:463–468. 2006.PubMed/NCBI
5	Ito M, Hiwasa T, Oshima Y, Yajima S, Suzuki T, Nanami T, Sumazaki M, Shiratori F, Funahashi K, Takizawa H, et al: Identification of serum anti-striatin 4 antibodies as a common marker for esophageal cancer and other solid cancers. Mol Clin Oncol. 15(237)2021.PubMed/NCBI View Article : Google Scholar
6	Sumazaki M, Shimada H, Ito M, Shiratori F, Kobayashi E, Yoshida Y, Adachi A, Matsutani T, Iwadate Y, Mine S, et al: Serum anti-LRPAP1 is a common biomarker for digestive organ cancers and atherosclerotic diseases. Cancer Sci. 111:4453–4464. 2020.PubMed/NCBI View Article : Google Scholar
7	Ito M, Hiwasa T, Oshima Y, Yajima S, Suzuki T, Nanami T, Sumazaki M, Shiratori F, Funahashi K, Li SY, et al: Association of serum anti-PCSK9 antibody levels with favorable postoperative prognosis in esophageal cancer. Front Oncol. 11(708039)2021.PubMed/NCBI View Article : Google Scholar
8	Ito M, Hiwasa T, Yajima S, Suzuki T, Oshima Y, Nanami T, Sumazaki M, Shiratori F, Li SY, Iwadate Y, et al: Low anti-CFL1 antibody with high anti-ACTB antibody is a poor prognostic factor in esophageal squamous cell carcinoma. Esophagus. 19:617–625. 2022.PubMed/NCBI View Article : Google Scholar
9	Daryabari SS, Fathi M, Mahdavi M, Moaddab Y, Hosseinpour Feizi MA, Shokoohi B and Safaralizadeh R: Overexpression of CFL1 in gastric cancer and the effects of its silencing by siRNA with a nanoparticle delivery system in the gastric cancer cell line. J Cell Physiol. 235:6660–6672. 2020.PubMed/NCBI View Article : Google Scholar
10	Li X, Ma G, Guo W, Mu N, Wang Y, Liu X and Su L: Hhex inhibits cell migration via regulating RHOA/CDC42-CFL1 axis in human lung cancer cells. Cell Commun Signal. 19(80)2021.PubMed/NCBI View Article : Google Scholar
11	Werle SD, Schwab JD, Tatura M, Kirchhoff S, Szekely R, Diels R, Ikonomi N, Sipos B, Sperveslage J, Gress TM, et al: Unraveling the molecular tumor-promoting regulation of cofilin-1 in pancreatic cancer. Cancers (Basel). 13(725)2021.PubMed/NCBI View Article : Google Scholar
12	Li J, Brieher WM, Scimone ML, Kang SJ, Zhu H, Yin H, von Andrian UH, Mitchison T and Yuan J: Caspase-11 regulates cell migration by promoting Aip1-Cofilin-mediated actin depolymerization. Nat Cell Biol. 9:276–286. 2007.PubMed/NCBI View Article : Google Scholar
13	Hu L, Liu J, Shimada H, Ito M, Sugimoto K, Hiwasa T, Zhou Q, Li J, Shen S and Wang H: Serum anti-BRAT1 is a common molecular biomarker for gastrointestinal cancers and atherosclerosis. Front Oncol. 12(870086)2022.PubMed/NCBI View Article : Google Scholar
14	Xu J, Wan P, Wang M, Zhang J, Gao X, Hu B, Han J, Chen L, Sun K, Wu J, et al: AIP1-mediated actin disassembly is required for postnatal germ cell migration and spermatogonial stem cell niche establishment. Cell Death Dis. 6(e1818)2015.PubMed/NCBI View Article : Google Scholar
15	Kagaya A, Shimada H, Shiratori T, Kuboshima M, Nakashima-Fujita K, Yasuraoka M, Nishimori T, Kurei S, Hachiya T, Murakami A, et al: Identification of a novel SEREX antigen family, ECSA, in esophageal squamous cell carcinoma. Proteome Sci. 9(31)2011.PubMed/NCBI View Article : Google Scholar
16	Konzok A, Weber I, Simmeth E, Hacker U, Maniak M and Muller-Taubenberger A: DAip1, a dictyostelium homologue of the yeast actin-interacting protein 1, is involved in endocytosis, cytokinesis, and motility. J Cell Biol. 146:453–464. 1999.PubMed/NCBI View Article : Google Scholar
17	Wang H, Zhang XM, Tomiyoshi G, Nakamura R, Shinmen N, Kuroda H, Kimura R, Mine S, Kamitsukasa I, Wada T, et al: Association of serum levels of antibodies against MMP1, CBX1, and CBX5 with transient ischemic attack and cerebral infarction. Oncotarget. 9:5600–5613. 2018.PubMed/NCBI View Article : Google Scholar
18	Sugimoto K, Mori M, Liu J, Shibuya K, Isose S, Koide M, Hiwasa T and Kuwabara S: Novel serum autoantibodies against β-actin (ACTB) in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 22:388–394. 2021.PubMed/NCBI View Article : Google Scholar
19	Shimada H, Shiratori T, Yasuraoka M, Kagaya A, Kuboshima M, Nomura F, Takiguchi M, Ochiai T, Matsubara H and Hiwasa T: Identification of makorin 1 as a novel SEREX antigen of esophageal squamous cell carcinoma. BMC Cancer. 9(232)2009.PubMed/NCBI View Article : Google Scholar
20	Machida T, Kubota M, Kobayashi E, Iwadate Y, Saeki N, Yamaura A, Nomura F, Takiguchi M and Hiwasa T: Identification of stroke-associated-antigens via screening of recombinant proteins from the human expression cDNA library (SEREX). J Transl Med. 13(71)2015.PubMed/NCBI View Article : Google Scholar
21	Li SY, Yoshida Y, Kobayashi E, Adachi A, Hirono S, Matsutani T, Mine S, Machida T, Ohno M, Nishi E, et al: Association between serum anti-ASXL2 antibody levels and acute ischemic stroke, acute myocardial infarction, diabetes mellitus, chronic kidney disease and digestive organ cancer, and their possible association with atherosclerosis and hypertension. Int J Mol Med. 46:1274–1288. 2020.PubMed/NCBI View Article : Google Scholar
22	Shimada H, Ochiai T and Nomura F: Japan p53 Antibody Research Group. Titration of serum p53 antibodies in 1,085 patients with various types of malignant tumors: A multiinstitutional analysis by the Japan p53 Antibody Research Group. Cancer. 97:682–689. 2003.PubMed/NCBI View Article : Google Scholar
23	Shimada H, Takeda A, Arima M, Okazumi S, Matsubara H, Nabeya Y, Funami Y, Hayashi H, Gunji Y, Suzuki T, et al: Serum p53 antibody is a useful tumor marker in superficial esophageal squamous cell carcinoma. Cancer. 89:1677–1683. 2000.PubMed/NCBI
24	Shimada H, Nabeya Y, Okazumi S, Matsubara H, Shiratori T, Gunji Y, Kobayashi S, Hayashi H and Ochiai T: Prediction of survival with squamous cell carcinoma antigen in patients with resectable esophageal squamous cell carcinoma. Surgery. 133:486–494. 2003.PubMed/NCBI View Article : Google Scholar
25	Camp RL, Dolled-Filhart M and Rimm DL: X-tile: A new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 10:7252–7259. 2004.PubMed/NCBI View Article : Google Scholar
26	Kanda Y: Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 48:452–458. 2013.PubMed/NCBI View Article : Google Scholar
27	Wang JW, Peng SY, Li JT, Wang Y, Zhang ZP, Cheng Y, Cheng DQ, Weng WH, Wu XS, Fei XZ, et al: Identification of metastasis-associated proteins involved in gallbladder carcinoma metastasis by proteomic analysis and functional exploration of chloride intracellular channel 1. Cancer Lett. 281:71–81. 2009.PubMed/NCBI View Article : Google Scholar
28	Lambert AW, Pattabiraman DR and Weinberg RA: Emerging biological principles of metastasis. Cell. 168:670–691. 2017.PubMed/NCBI View Article : Google Scholar
29	Kim DH, Bae J, Lee JW, Kim SY, Kim YH, Bae JY, Yi JK, Yu MH, Noh DY and Lee C: Proteomic analysis of breast cancer tissue reveals upregulation of actin-remodeling proteins and its relevance to cancer invasiveness. Proteomics Clin Appl. 3:30–40. 2009.PubMed/NCBI View Article : Google Scholar
30	Izawa S, Okamura T, Matsuzawa K, Ohkura T, Ohkura H, Ishiguro K, Noh JY, Kamijo K, Yoshida A, Shigemasa C, et al: Autoantibody against WD repeat domain 1 is a novel serological biomarker for screening of thyroid neoplasia. Clin Endocrinol. 79:35–42. 2013.PubMed/NCBI View Article : Google Scholar
31	Haslene-Hox H, Oveland E, Woie K, Salvesen HB, Wiig H and Tenstad O: Increased WD-repeat containing protein 1 in interstitial fluid from ovarian carcinomas shown by comparative proteomic analysis of malignant and healthy gynecological tissue. Biochim Biophys Acta. 1834:2347–2359. 2013.PubMed/NCBI View Article : Google Scholar
32	Xu H, Chen Y, Tan C, Xu T, Yan Y, Qin R, Huang Q, Lu C, Liang C, Lu Y, et al: High expression of WDR1 in primary glioblastoma is associated with poor prognosis. Am J Transl Res. 8:1253–1264. 2016.PubMed/NCBI
33	Talman AM, Chong R, Chia J, Svitkina T and Agaisse H: Actin network disassembly powers dissemination of Listeria monocytogenes. J Cell Sci. 127(Pt 1):240–249. 2014.PubMed/NCBI View Article : Google Scholar
34	Shoji K, Ohashi K, Sampei K, Oikawa M and Mizuno K: Cytochalasin D acts as an inhibitor of the actin-cofilin interaction. Biochem Biophys Res Commun. 424:52–57. 2012.PubMed/NCBI View Article : Google Scholar
35	Utomo DH, Fujieda A, Tanaka K, Takahashi M, Futaki K, Tanabe K, Kigoshi H and Kita M: The C29-C34 parts of antitumor macrolide aplyronine A serve as versatile actin-affinity tags. Chem Commun (Camb). 57:10540–10543. 2021.PubMed/NCBI View Article : Google Scholar
36	Japan Esophageal Society. Japanese classification of esophageal cancer, 11th Edition: Part II and III. Esophagus. 14:37–65. 2017.PubMed/NCBI View Article : Google Scholar