Conserved serum protein biomarkers associated with growing early colorectal adenomas

Abstract

A major challenge for the reduction of colon cancer is to detect patients carrying high-risk premalignant adenomas with minimally invasive testing. As one step, we have addressed the feasibility of detecting protein signals in the serum of patients carrying an adenoma as small as 6–9 mm in maximum linear dimension. Serum protein biomarkers, discovered in two animal models of early colonic adenomagenesis, were studied in patients using quantitative mass-spectrometric assays. One cohort included patients bearing adenomas known to be growing on the basis of longitudinal computed tomographic colonography. The other cohort, screened by optical colonoscopy, included both patients free of adenomas and patients bearing adenomas whose risk status was judged by histopathology. The markers F5, ITIH4, LRG1, and VTN were each elevated both in this patient study and in the studies of the Pirc rat model. The quantitative study in the Pirc rat model had demonstrated that the elevated level of each of these markers is correlated with the number of colonic adenomas. However, the levels of these markers in patients were not significantly correlated with the total adenoma volume. Postpolypectomy blood samples demonstrated that the elevated levels of these four conserved markers persisted after polypectomy. Two additional serum markers rapidly renormalized after polypectomy: growth-associated CRP levels were enhanced only with high-risk adenomas, while PI16 levels, not associated with growth, were reduced regardless of risk status. We discuss biological hypotheses to account for these observations, and ways for these signals to contribute to the prevention of colon cancer.

Plasma Inter-Alpha-Trypsin Inhibitor Heavy Chains H3 and H4 Serve as Novel Diagnostic Biomarkers in Human Colorectal Cancer

“…In a rat model, ITIH 4 was upregulated in early intestinal tumors, indicative of a role in extracellular matrix remodeling in colon tumor tissue [16]. In addition, the elevated level of serum ITIH 4 was associated with early colonic adenomagenesis, which served as the most important premalignant state for CRC [17]. These results indicate that upregulation of plasma ITIH 4 is closely related to the carcinogenesis of CRC, supporting its utility as an indicator of tumorigenesis in clinical practice.…”

“…Additionally, ITIH 4 was shown to be upregulated in plasma of mice with severe colitis [15] and had high sensitivity and specificity in the identification of early-stage colon adenoma [16]. Furthermore, the ITIH 4 level was significantly elevated in THE serum of patients growing early colorectal adenomas, which was identified as a premalignant state [17]. Considering that there have been no studies aiming at ITIH 3 /ITIH 4 in the human plasma of CRC, we therefore selected the two proteins as plasma biomarkers to determine their association with CRC risk.…”

Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis of Adult-Onset Still’s Disease

“…α-1-acid glycoprotein 1, encoding leucine-rich α-2-glycoprotein 1, is a secreted protein belonging to the leucine-rich repeat (LRR) family. LRG1 is abundant in human serum, mainly produced by hepatocytes, and is involved in the pathogenesis of tumorigenesis and angiogenesis ( 24 , 25 ). Recently, LRG1 has been recognized as a proinflammatory marker and found to be elevated in patients with ulcerative colitis, type 1 diabetes or RA ( 26 – 29 ).…”

Study on the Diagnosis of Gastric Cancer by Magnetic Beads Extraction and Mass Spectrometry

“…Otherwise, it cannot be effectively detected. Recently, with the rapid development of biomass spectrometry technology, serum peptides, which used to be considered as biological waste, have become a hot spot in screening tumor blood markers [ 5 , 6 , 11 – 13 ]. In this study, 122 peptide peaks were obtained through by analysed the serum peptide expression profile in 20 healthy patients and 20 gastric cancer patients with MALDI-TOF MS.…”

“…This is the first study of serum peptide as a tumor marker. In recent years, with the rapid development of biomass spectrometry technology, serum peptides, which used to be considered as biological waste, has become a hot spot in screening tumor blood markers [5,6]. Therefore, the value of serum peptides in tumor diagnosis has been gradually recognized.…”