Autoantibodies as biomarkers for colorectal cancer: A systematic review, meta-analysis, and bioinformatics analysis

Abstract

Colorectal cancer is a very common cancer worldwide. Serum tumor-associated autoantibodies (TAAbs), especially the anti-p53 autoantibody, may be promising biomarkers to detect early-stage colorectal cancer. This study aimed to identify all known autoantibodies and their value in colorectal cancer diagnosis, as well as exploring the underlying connections and mechanisms through a bioinformatics analysis. Databases were used to select available articles of TAAbs in colorectal cancer. In a meta-analysis of the anti-p53 autoantibody, the diagnostic odds ratio and area under the curve (AUC) of the summary receiver-operating characteristic (SROC) curve were calculated using Stata 12.0 and Meta-Disc 1.4. We identified 73 articles including 199 single autoantibodies and 42 multiple autoantibodies. The maximum value of Youden's index was 0.76, combining c-MYC, p53, cyclin B1, p62, Koc, IMP1, and survivin. The diagnostic odds ratio for anti-p53 autoantibody at all stages was 10.86 (95% CI 8.40, 14.06) with low heterogeneity (I 2 = 40.3%) and the AUC of the SROC curve was 0.82. For the anti-p53 autoantibody in early-stage colorectal cancer, the diagnostic odds ratio was 4.82 (95% CI 2.95, 7.87) with heterogeneity (I 2 = 7.9%) and the AUC of the SROC curve was 0.72. Eighty-seven autoantibodies were selected for bioinformatics analyses. We found that the most enriched functional terms and protein-protein interactions may relate to the mechanism of autoantibody generation. In summary, our study summarized the diagnostic value of TAAbs in colorectal cancer, either as single molecules or in combination. Bioinformatics analyses may be a new approach to explore the mechanism of autoantibody generation.

Anti-Cancer Auto-Antibodies: Roles, Applications and Open Issues

“…p53 has also been found to be an autoantigen in colorectal cancer and, in a metaanalysis considering 199 antigens, it was found to be an important auto-antibody for diagnostic purposes in combination with those against c-MYC, cyclin B1, p62, Koc, IMP1, and survivin [42]. Even alone, p53 auto-antibodies were able to predict the likelihood to develop colorectal cancer within 6 years [43], although their presence at recurrence was not found to be a relevant prognostic factor [44].…”

Identification and Validation of Novel Serum Autoantibody Biomarkers for Early Detection of Colorectal Cancer and Advanced Adenoma

“…(3) Autoantibodies against HSP60, CENPF, RGN, PRDX3, ACY1, ANXA4, and HINT1 that have been studied in hepatocellular carcinoma (15) and showed discrepancies in CRC in our preliminary experiments. (4) Autoantibodies against RPL13, RPH3AL, HMGN3, MPHOSPH6, IGF2BP1, VIL1, AIF1, CALR, CTAG1, and MYH13 based on previous systematic reviews of autoantibodies in CRC (12,13).…”

“…Therefore, autoantibodies have been proposed as biomarkers for early-stage detection of cancers. In recent years, autoantibodies against TAAs have been reported in patients with CRC, but only by a series of studies on small cohorts and without high-throughput screening in a large cohort of samples especially advanced adenoma (AA), an advanced precancerous lesion ( 12 , 13 ).…”

Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma

“…The immune system responds to these non-self antigens, producing specific autoantibodies. Tumor-associated (TA) autoantibodies have been observed in patients with various tumors, including breast [4], prostate [5,6], lung [7], colorectal [8], ovarian [9,10], and liver [11], and have become of interest as cancer biomarkers because they can be easily detected in serum via minimally invasive blood collection [3].…”