Clinical significance of serum autoantibodies against Ras-like GTPases, RalA, in patients with esophageal squamous cell carcinoma
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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.
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.
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.
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.
KeywordsRalA Serum autoantibody Tumor marker Esophageal cancer ELISA
Squamous cell carcinoma
Serum RalA antibodies
Serum p53 antibodies
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.
Compliance with ethical standards
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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