Serum anti-POTEE antibodies as a novel serological biomarker for early detection and prognostic stratification in gastrointestinal cancers

Abstract

Abstract Background Given the highly aggressive nature of gastrointestinal cancers, the identification of novel biomarkers for diagnosis and prognosis is of considerable clinical importance. Methods Candidate cancer-testis (CT) antigens were first screened using RNA-sequencing data from normal human tissues; candidates showing high commonality across tumor RNA-sequencing datasets publicly available in The Cancer Genome Atlas were subsequently prioritized, and POTEE was identified as a promising target. Recombinant POTEE protein was expressed in Escherichia coli, purified by affinity chromatography, and used as the antigen for serological analysis. Results Serum levels of anti-POTEE antibodies (s-POTEE-Abs) were significantly elevated in 121 patients with esophageal squamous cell carcinoma, 62 patients with gastric adenocarcinoma, and 158 patients with colorectal adenocarcinoma compared with those in 96 healthy donors. Receiver operating characteristic curve analysis showed that the diagnostic performance of s-POTEE-Ab was comparable to that of s-p53-Ab, with area under the curve values of 0.832 versus 0.829 in esophageal squamous cell carcinoma, 0.680 versus 0.698 in gastric adenocarcinoma, and 0.735 versus 0.706 in colorectal adenocarcinoma, respectively. In survival analyses, s-POTEE-Ab positivity was associated with poorer overall survival in ESCC and CRAC, but not in GAC. After multivariable adjustment, an independent prognostic association was retained only in CRAC. Conclusions These findings suggest that s-POTEE-Ab may represent a promising exploratory serological biomarker for gastrointestinal cancers. Its prognostic relevance appears to be cancer-type dependent and requires further validation in independent cohorts.