Plasma Protein Profiling Reveal Osteoprotegerin as a Marker of Prognostic Impact for Colorectal Cancer

Abstract

BACKGROUND: Due to difficulties in predicting recurrences in colorectal cancer stages II and III, reliable prognostic biomarkers could be a breakthrough for individualized treatment and follow-up. OBJECTIVE: To find potential prognostic protein biomarkers in colorectal cancer, using the proximity extension assays. METHODS: A panel of 92 oncology-related proteins was analyzed with proximity extension assays, in plasma from a cohort of 261 colorectal cancer patients with stage II-IV. The survival analyses were corrected for disease stage and age, and the recurrence analyses were corrected for disease stage. The significance threshold was adjusted for multiple comparisons. RESULTS: The plasma proteins expression levels had a greater prognostic relevance in disease stage III colorectal cancer than in disease stage II, and for overall survival than for time to recurrence. Osteoprotegerin was the only biomarker candidate in the protein panel that had a statistical significant association with overall survival (P = .00029). None of the proteins were statistically significantly associated with time to recurrence. CONCLUSIONS: Of the 92 analyzed plasma proteins, osteoprotegerin showed the strongest prognostic impact in patients with colorectal cancer, and therefore osteoprotegerin is a potential predictive marker, and it also could be a target for treatments.

Systemic inflammation in colorectal cancer: Underlying factors, effects, and prognostic significance

“…Recently, using proximity extension assays, Birgisson et al[20] analyzed plasma levels of 92 oncology-related proteins, including an assemblage of cytokines, chemokines, and growth factors, in a cohort of 261 stage II-IV CRC patients. Many of these molecules, including CSF1, CXCL10, CXCL9, HGF (hepatocyte growth factor), IL6, osteoprotegerin, PGF (placental growth factor), and VEGFA, were significantly associated with survival in univariable analysis, and of these, osteoprotegerin was the best in predicting survival in multivariable survival models[20]. Analyzing multiple markers in one sample may improve the prognostic power relative to measuring the levels of a single marker.…”

“…Many markers of systemic inflammation are based on counts, ratios, or scores of circulating white cells or acute phase proteins, such as neutrophil/lymphocyte ratio (NLR) and Modified Glasgow Prognostic score (mGPS), a measure based on elevated serum CRP level and decreased serum albumin level[17], but more recent studies have also evaluated the significance of alterations in circulating cytokine, chemokine, and growth factor milieu[18-20], platelet transcriptome[21], or the composition of tumor-derived extracellular vesicles[22]. Released by tumor cells or non-neoplastic cells in tumor-elicited host reaction, IL6 (interleukin-6) is one of the most important mediators of systemic effects of inflammation, such as the production of acute phase proteins in the liver[15] and in cancer cachexia[16].…”

Plasma protein biomarkers for early detection of pancreatic ductal adenocarcinoma

“…To meet this challenge, we analyzed plasma samples using the proximity extension assay (PEA), which enables high‐throughput, multiplex immunoassays that measure multiple proteins simultaneously on smaller volume of samples than general methods. This technology uses fixed panels of protein biomarkers that have been suggested as generic biomarker candidates for different diseases, such as colorectal cancer, 12 breast cancer, 13 heart disease and diabetes 14 . Our aim was to investigate whether the selected protein biomarkers could discriminate PDAC, especially in early stage, from healthy control individuals as well as chronic pancreatitis patients.…”

Correlation between IL-10 as Cancer Biomarker and Demographic Characteristics of Colorectal Cancer Patients

“…In recent, many studies have shown that circulating cytokine levels gave prognostic information in CRC patients. And these proinflammatory cytokines have a significant role in tumor growth and progression [23,24]. The massive release of these cytokines and the acute phase protein to the CRC circulating system is considered a hallmark for this cancer type [25].…”