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Clinical significance of serum autoantibodies against Ras-like GTPases, RalA, in patients with esophageal squamous cell carcinoma

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Abstract

Background

The Ras-like GTPases, RalA and RalB are members of the Ras superfamily of small GTPases. Aberrant activation of Ral is a major cause of human tumorigenesis induced by oncogenic Ras. Serum anti-RalA antibodies are induced in esophageal carcinoma patients. However, detailed comparisons of their pathological characteristics are unavailable, and conventional serum markers have not been well evaluated.

Methods

Serum samples of 171 patients with esophageal squamous cell carcinoma and 73 healthy individuals were analyzed using specifically developed ELISA system for serum anti-RalA antibodies. A cut-off optical density value was fixed at 0.255 (the control mean + 2 SD). Clinicopathological characteristics and positive rates of conventional tumor markers were evaluated for seropositive patients.

Results

Overall positive rate for serum anti-RalA antibodies was 18 %, which gradually increased with the tumor stages. Although the positive rate for serum anti-RalA antibodies was comparable with that of carcinoembryonic antigen (24 %) and CYFRA21-1 (21 %), it was lower than the rate for serum p53 antibodies (31 %) and squamous cell carcinoma antigen (37 %). Although serum anti-RalA antibodies were not associated with other serum markers, it was inversely associated with serum p53 antibodies. No clear association was observed between serum anti-RalA antibodies and RalA immunoreactivity.

Conclusions

Presence of serum anti-RalA antibodies is associated with tumor stages, but not with conventional tumor markers. Serum anti-RalA antibodies may be candidate serum markers in combination with other serum markers for esophageal squamous cell carcinoma.

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Abbreviations

CEA:

Carcinoembryonic antigen

SCC:

Squamous cell carcinoma

OD:

Optical density

s-RalA-Abs:

Serum RalA antibodies

s-p53-Abs:

Serum p53 antibodies

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Acknowledgments

This research was partly supported by Grant-in-Aid for Scientific Research (Nos. 24591961 and 21591717) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Department of Surgery, School of Medicine, Toho University, Tokyo, Japan

    Tatsuki Nanami, Hideaki Shimada, Satoshi Yajima, Yoko Oshima, Seiko Otsuka & Hironori Kaneko

  2. Department of Molecular Diagnosis, Chiba University, Graduate School of Medicine, Chiba, Japan

    Kazuyuki Matsushita & Fumio Nomura

  3. Division of Gastroenterological Surgery, Chiba Cancer Center, Chiba, Japan

    Matsuo Nagata

  4. Division of Pathology and Cell Therapy, Chiba Cancer Center, Chiba, Japan

    Masatoshi Tagawa

  5. Medical & Biological Laboratories Co., Ltd., Nagoya, Japan

    Akiko Kuwajima

Authors
  1. Tatsuki Nanami
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  2. Hideaki Shimada
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  3. Satoshi Yajima
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  4. Yoko Oshima
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  5. Kazuyuki Matsushita
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  7. Matsuo Nagata
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  10. Akiko Kuwajima
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  11. Hironori Kaneko
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Corresponding author

Correspondence to Hideaki Shimada.

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Ethical Statement

This study was approved by the institutional review boards of Chiba Cancer Center (#21-26) and Toho University School of Medicine (#22-112, #22-047). Additional informed consent was obtained from all patients for whom identifying information is included in this article.

Conflict of Interest

Hideaki Shimada received research grants and technical lecture fees form Medical & Biological Laboratories Co., Ltd., Nagoya, Japan. Akiko Kuwajima is an employee of Medical & Biological Laboratories Co., Ltd., Nagoya, Japan. The other authors have no conflict of interest.

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Nanami, T., Shimada, H., Yajima, S. et al. Clinical significance of serum autoantibodies against Ras-like GTPases, RalA, in patients with esophageal squamous cell carcinoma. Esophagus 13, 167–172 (2016). https://doi.org/10.1007/s10388-015-0510-8

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  • DOI: https://doi.org/10.1007/s10388-015-0510-8

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