Elevated Serum Levels of Circulating Immunoinflammation-Related Protein Complexes Are Associated with Cancer

Abstract

Disease-specific immune response-related protein complexes in the bloodstream are associated with disease status. We used proteomic technologies to screen novel circulating immunoinflammation-related protein complexes (IIRPCs) and to evaluate their diagnostic accuracy. The discovery study included 96 gastric cancer patients and 83 healthy controls and was designed to isolate and identify the IIRPCs. Then an independent validation study including 1366 patients with lung, colorectal, pancreatic, gastric, or thyroid cancer, 141 patients with other types of cancer, 376 patients with benign lung, colorectal, pancreatic, gastric, or thyroid diseases, and 3707 healthy controls was performed. We observed seven major patterns of the IIRPCs and confirmed the IIRPCs as personalized biomarkers of cancers. The levels of the IIRPCs were significantly increased in cancer patients compared with controls and benign patients (p < 0.0001). Each of the IIRPCs (a2 to a4, a6, a7, and b3 to b5) shows excellent discriminating power for lung, colorectal, pancreatic, and gastric cancer, with the areas under the receiver operating characteristic curves (AUCs) from 0.95 to 0.99 (95% CIs 0.91-1.00), and for thyroid cancer, with the AUCs from 0.87 to 0.96 (95% CIs 0.80-0.98). The IIRPCs can be used as a novel type of broad-spectrum and supramolecular biomarker for personalized cancer diagnosis.

Disease-specific IgG Fc N-glycosylation as personalized biomarkers to differentiate gastric cancer from benign gastric diseases

“…Recently, emerging evidence indicates that changes in the glycosylation of total serum IgG isolated using Protein A or Protein G are associated with pathophysiological states 30 31 32 33 34 35 . In this study, we employ our developed approach to obtain DSIgG, which only exists in patients with chronic diseases 26 . Mass spectrometric analysis indicated that DSIgG is mainly composed of two subclasses of IgG1 and IgG2.…”

“…2 GC patients and 13 BGD patients without the information of sex or age were excluded before the native-PAGE separation. The remaining serum samples from 510 GC patients and 512 BGD patients were separated using an optimized native-PAGE as previously described 26 . It was found that 107 GC patients and 69 BGD patients had no IIRPCs and excluded in the following study 26 .…”

“…The remaining serum samples from 510 GC patients and 512 BGD patients were separated using an optimized native-PAGE as previously described 26 . It was found that 107 GC patients and 69 BGD patients had no IIRPCs and excluded in the following study 26 . Finally, 403 GC serum samples and 443 BGD serum were selected for the further experiments.…”

“…Native-PAGE was performed on the basis of the approach described previously with slight modifications 26 . Briefly, 5 μL serum was separated with the electrophoresis system consisted of separating gel (4% to 10% gradient acrylamide gel) and stacking gel (4%) to obtain serum IIRPCs.…”

“…Our previous studies have found that serum immunoinflammation-related protein complexes (IIRPCs) are closely associated with disease states, disease types, and the progression of lung cancer 26 27 28 . Their major components are complements, haptoglobin, immunoglobulin A, and IgG.…”