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Low anti-CFL1 antibody with high anti-ACTB antibody is a poor prognostic factor in esophageal squamous cell carcinoma

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Abstract

Background

Cofilin (CFL1, actin-binding protein) and β-actin (ACTB) are key molecules in the polymerization and depolymerization of actin microfilaments. The levels of these antibodies were analyzed, and the clinicopathological significance in patients with esophageal carcinoma were evaluated.

Methods

The levels of anti-CFL1 and anti-ACTB antibodies were analyzed in serum samples of patients with esophageal carcinoma and of healthy donors. Eighty-seven cases underwent radical surgery and the clinicopathological characteristics and prognosis was examined.

Results

Serum anti-CFL1 antibody (s-CFL1-Ab) levels and anti-ACTB antibody (s-ACTB-Ab) levels were significantly higher in patients with esophageal carcinoma than in healthy donors. Following the receiver operating characteristic curve analysis between healthy donors and esophageal carcinoma, the sensitivity and specificity for serum anti-CFL1 antibody (s-CFL1-Ab) were 53.3% and 68.8%. The sensitivity and specificity for serum anti-ACTB antibody (s-ACTB-Ab) were 54.9% and 67.7%, respectively. Univariate and multivariate analysis showed that s-CFL1-Ab and s-ACTB-Ab levels were not associated with sex, age, tumor depth, lymph node metastasis, or anti-p53-antibody levels. s-ACTB-Ab levels but not s-CFL1-Ab levels significantly correlated with squamous cell carcinoma antigen. Neither s-CFL1-Ab nor s-ACTB-Ab levels alone were obviously related to overall survival. However, patients with low s-CFL1-Ab levels and high s-ACTB-Ab levels exhibited significantly more unfavorable prognoses than those with high s-CFL1-Ab and low s-ACTB-Ab levels.

Conclusions

Serum levels of anti-CFL1 and anti-ACTB antibodies were significantly higher in patients with esophageal carcinoma than in healthy donors. A combination of low anti-CFL1 and high anti-ACTB antibodies is a poor prognostic factor in esophageal carcinoma.

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Acknowledgements

We thank professor Kimihiko Funahashi, MD., PhD. for supporting our study. And we also thank Ms. Seiko Otsuka, Ms. Masae Suzuki, Ms. Chiho Kusaka, and Ms. Satoko Ishibashi for preparing patient data.

Funding

This research was supported by the Project for Cancer Research and Therapeutic Evolution (P-CREATE) from the Japan Agency for Medical Research and Development, AMED (grant no. 21cm0106403h0006) and Grants-in-Aid for Scientific Research (KAKENHI) from the Japan Society for the Promotion of Science, JSPS (grant no. 16K10520 and 20K16396).

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Authors and Affiliations

  1. Department of Gastroenterological Surgery and Clinical Oncology, Toho University Graduate School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan

    Masaaki Ito, Takaki Hiwasa & Hideaki Shimada

  2. Department of Neurological Surgery, Chiba University Graduate School of Medicine, Chiba, 260-8670, Japan

    Takaki Hiwasa, Shu-Yang Li & Yasuo Iwadate

  3. Department of Gastroenterological Surgery, Toho University School of Medicine, Tokyo, Japan

    Satoshi Yajima, Takashi Suzuki, Yoko Oshima, Tatsuki Nanami, Makoto Sumazaki, Fumiaki Shiratori & Hideaki Shimada

  4. Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan

    Kazuo Sugimoto, Masahiro Mori & Satoshi Kuwabara

  5. Port Square Kashiwado Clinic, Kashiwado Memorial Foundation, Chiba, 260-0025, Japan

    Hirotaka Takizawa

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  1. Masaaki Ito
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Contributions

TH, HS, YI, and MI did conceptualization; SYL, KS, MM, and SK did methodology; SYL validated the study; YO, SY, TS, TN, FS, and HT did data curation; MI, TH, and HS wrote the manuscript; HS did funding acquisition. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Hideaki Shimada.

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Ethical statement

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Toho University, Graduate School of Medicine (No. A18103_A17052_A16035_A16001_26095_25024_24038_22047_22047) and Chiba University Graduate School of Medicine (No. 2018-320) (Japan) and co-operated hospitals. We collected sera from patients who had provided written informed consent.

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The authors declare no conflict of interest.

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Supplementary Information

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10388_2022_939_MOESM1_ESM.docx

Supplementary file1 (DOCX 52 kb) Comparison of serum anti-ACTB antibody (s-ACTB-Ab) and serum anti-CFL1 antibody (s-CFL1-Ab) levels between solid cancers and healthy donors. The levels of s-CFL1-Abs and s-ACTB-Abs in healthy donors (n = 96) and patients with gastric cancer (n = 96) and colorectal cancer (n = 192) were examined by AlphaLISA and are shown in box-whisker plots. The serum samples were collected before treatment including all pathological stages. Treatment methods were not limited to surgery. Box plot represents 25, 50 and 75 percentiles. The upper and lower horizontal lines represent 90 and 10 percentiles, respectively. ***, P <0.001; **, P <0.01, *, P <0.05; evaluated with the Kruskal–Wallis test with Bonferroni’s correction applied

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Ito, M., Hiwasa, T., Yajima, S. 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). https://doi.org/10.1007/s10388-022-00939-0

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  • DOI: https://doi.org/10.1007/s10388-022-00939-0

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