Abstract
Simple SummaryImmunome in Sporadic Colorectal Cancer as source for biomarkers. Hence, a self-assembled protein array has been designed and developed to perform a serum screening to determined specific immune response against tumor antigens proteins as potential diagnostics biomarker panel.Sporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expression levels, which contribute to the development of sCRC. Then, the tumor-associated proteins (TAAs) might induce the production of auto-antibodies (aAb) via humoral immune response. Here, Nucleic Acid Programmable Protein Arrays (NAPPArray) are employed to identify aAb in plasma samples from a set of 50 sCRC patients compared to seven healthy donors. Our goal was to establish a systematic workflow based on NAPPArray to define differential aAb profiles between healthy individuals and sCRC patients as well as between non-metastatic (n = 38) and metastatic (n = 12) sCRC, in order to gain insight into the role of the humoral immune system in controlling the development and progression of sCRC. Our results showed aAb profile based on 141 TAA including TAAs associated with biological cellular processes altered in genesis and progress of sCRC (e.g., FSCN1, VTI2 and RPS28) that discriminated healthy donors vs. sCRC patients. In addition, the potential capacity of discrimination (between non-metastatic vs. metastatic sCRC) of 7 TAAs (USP5, ML4, MARCKSL1, CKMT1B, HMOX2, VTI2, TP53) have been analyzed individually in an independent cohort of sCRC patients, where two of them (VTI2 and TP53) were validated (AUC ~75%). In turn, these findings provided novel insights into the immunome of sCRC, in combination with transcriptomics profiles and protein antigenicity characterizations, wich might lead to the identification of novel sCRC biomarkers that might be of clinical utility for early diagnosis of the tumor. These results explore the immunomic analysis as potent source for biomarkers with diagnostic and prognostic value in CRC. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these novel sCRC immunomic biomarkers.
Highlights
Sporadic colorectal cancer is the third leading cause of cancer death in the Western world [1]
Quality control (QC) assays of NAPPArray were performed in order to assess the reproducibility and robustness of the NAPPAarray platform in the screening of aAb presented in Sporadic colorectal cancer (sCRC) plasma samples
The results showed that 7% (141 out of 2023) of unique tumor-associated antigens (TAA) displayed in the NAPPArray allowed discrimination between healthy donors and sCRC patients
Summary
Sporadic colorectal cancer (sCRC) is the third leading cause of cancer death in the Western world [1]. Alternative cost-effective approaches based on fecal occult blood testing, measurement of carcinoembryonic antigen (CEA) serum levels, and/or testing for KRAS point mutations in liquid biopsies and/or circulating tumoral DNA (ctDNA) have been adopted or considered for current and future population-based sCRC screening programs. Their actual benefit is still a controversial topic, mainly due to the relatively high rate of both false positive and negative results [5]. The search for an alternative, complementary cost-effective and efficient approaches, suitable for the diagnostic screening of sCRC patients, still remains a challenge
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