Autoimmunity Profiles as Prognostic Indicators in Patients with Colorectal Cancer versus Those with Cancer at Other Sites: A Prospective Study

SIMPLE SUMMARY: The clinical utility of tumor-associated autoantibodies (TAABs) detected in patient sera with different types of cancer has not yet been established. Their possible use in early cancer detection, oncological follow-up, and patient prognosis is highly desirable. We developed a prospective study to investigate the role of TAABs in a five-year survival analysis in different types of cancer patients. Overall, overproduction of TAABs is associated with advanced oncological disease, the presence of metastasis, and poorer prognosis of cancer patients. There is evidence that more intensive follow-up programs provide different results for colorectal cancer than other cancers, because more intensive follow-up improves survival and is cost-effective in colorectal cancer. It is necessary to emphasize that there are many important aspects of follow-up in addition to detection of recurrence, and this must lead to proposals to change the way follow-up care is delivered. ABSTRACT: Colorectal cancer represents a paradigmatic model of inflammatory carcinogenesis accompanied by the production of several kinds of tumor-associated autoantibodies (TAABs). The specific aim of this study is to define the clinical impact of the presence of non-specific circulating TAABs in a cohort of cancer patients and to establish whether significant differences were present between colorectal cancer and cancers at other sites. For this aim a prospective study was developed and a five-year survival analysis performed. Indirect immunofluorescence on rat tissues for non-organ specific autoantibodies (NOSAs: liver-kidney-stomach), on rat colon substrates (colon-related autoantibodies, CAAs) and on HEp-2 cell lines was performed. NOSA positivity was more frequent in patients with colorectal cancer than in those with cancer at other sites. Survival analysis demonstrated a significantly worse prognosis in cancer patients positive for TAABs. CAA positivity is a predictor of survival, independently from the presence of comorbidities, and HEp-2 reactivity was a strong predictor of survival in a stepwise Cox-regression model, including stage at diagnosis. Overall overproduction of TAABs is associated with advanced oncological disease, the presence of metastasis, and poorer prognosis of cancer patients.