Detection of colorectal adenoma and cancer based on transthyretin and C3a‐desArg serum levels

Abstract

Colorectal cancer is the second leading cause of cancer death, and it develops from benign colorectal adenomas in over 95% of patients. Early detection of these cancer precursors by screening tests and their removal can potentially eradicate more than 95% of colorectal cancers before they develop. To discover sensitive and specific biomarkers for improvement of pre-clinical diagnosis of colorectal adenoma and cancer, we analysed in two independent studies (n = 87 and n = 83 patients) serum samples from colorectal cancer (stage III), colorectal adenoma and control patients using SELDI-TOF-MS. Extensive statistical analysis was performed to establish homogeneous patient groups based on their clinical data. Two biomarkers that were each able to distinguish control patients from either colorectal adenoma or colorectal cancer patients (p<0.001) were identified as transthyretin (pre-albumin) and C3a-desArg by MS/MS and were further validated by antibody-based assays (radial immunodiffusion, ELISA). A combination of both proteins clearly indicated the presence of colorectal adenoma or carcinoma. Using a cut-off of <0.225 g/L for transthyretin and >1974 ng/mL for C3a-desArg, we found a sensitivity and specificity for colorectal adenoma of 96% and 70%, respectively.

Identification of potential complementary serum biomarkers to differentiate prostate cancer from benign prostatic hyperplasia using gel‐ and lectin‐based proteomics analyses

“…Due to their nonspecific functions and association with diverse pathological conditions, APOA2 and C3f may not be suitable for use as independent biomarkers. Nonetheless, it is interesting to note that the 9‐kDa C3 cleaved fragment, C3a, has been reported to be elevated in patients with hepatocellular carcinoma [], breast cancer [], and colorectal cancer []. This is compatible with the diminished amounts of C3 seen in the PCa patients in this study.…”

“…While this is ambiguous for AAT, it is not totally unexpected for TTR as the protein is rather promiscuous in its interaction and is known to bind to many aromatic compounds []. TTR has been earlier identified as a potential biomarker for ovarian [], colorectal [], and lung [] cancers. It may have been retained by the CGB lectin affinity column in this study via its interaction with retinol–retinol binding protein 4 (RBP4) complex, although it is currently not known if RBP4 is indeed O ‐glycosylated.…”

Quantification of Serum Proteins of Metastatic Oral Cancer Patients Using LC-MS/MS and iTRAQ Labeling

“…(2) depicts the PQD spectrum for a tryptic peptide, GSPAINVAVHVFR, originated from transthyretin (TTR). TTR is a thyroid hormone-binding protein and has been associated with lung and colon cancers previously [8][9][10][11]. Our study suggested that TTR was overexpressed in non-metastatic OSCC as compared to metastatic OSCC.…”

Low‐mass‐ion discriminant equation: A new concept for colorectal cancer screening

“…Therefore, discriminating power of fibrinogen α chain may be restricted to any of diseases accompanying inflammation, rather than only to CRC, and additional identification of LMIs in CRC LOME 2 becomes a pressing issue. Transthyretin, meanwhile, is a supportive marker for colorectal adenoma and cancer that represents nutritional status . Including these two proteins, the combination of unidentified metabolic compounds may serve to characterize CRC.…”