Protein Biomarkers of Gastric Preneoplasia and Cancer Lesions in Blood: A Comprehensive Review

Abstract

Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. It is often associated with a bad prognosis because of its asymptomatic phenotype until advanced stages, highlighting the need for its prevention and early detection. GC development is preceded by the emergence of gastric preneoplasia lesions (GPNLs), namely atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia (DYS). GC is currently diagnosed by endoscopy, which is invasive and costly and has limited effectiveness for the detection of GPNLs. Therefore, the discovery of non-invasive biomarkers in liquid biopsies, such as blood samples, in order to identify the presence of gastric preneoplasia and/or cancer lesions at asymptomatic stages is of paramount interest. This comprehensive review provides an overview of recently identified plasma/serum proteins and their diagnostic performance for the prediction of GPNLs and early cancer lesions. Autoantibodies appear to be promising biomarkers for AG, IM and early gastric cancer detection, along with inflammation and immunity-related proteins and antibodies against H. pylori virulence factors. There is a lack of specific protein biomarkers with which to detect DYS. Despite the need for further investigation and validation, some emerging candidates could pave the way for the development of reliable, non-invasive diagnostic tests for the detection and prevention of GC.

Keywords: atrophic gastritis; diagnosis; dysplasia; early gastric cancer; intestinal metaplasia; liquid biopsy; plasma/serum; prevention; proteins.

Figure 1

(A) Histologic and endoscopic characteristics of gastric lesions during gastric carcinogenesis. Gastric histologic lesions obtained from gastric biopsies, H&E staining (a,c,e,f,h) and examination in NBI (b,d,g) and White Light. (i) Olympus endoscopy without optical zoom. Lesions of gastric atrophy (a,b). a (17.4×): chronic follicular atrophic non-metaplastic gastritis (complete atrophy). b: glandular atrophy shows pale appearance of gastric mucosa (green arrow), increased visibility of vasculature due to thinning of the gastric mucosa (red arrows), and loss of gastric folds. Lesions of intestinal metaplasia (c,d). c (9.4×): chronic atrophic and metaplastic gastritis (severe atrophy, severe intestinal metaplasia). d: intestinal metaplasia (red arrows) in gastric corpus. Rounded to branched pit pattern, with mucosa slightly darker than adjacent mucosa. Green arrows show normal gastric corpus mucosa, with round pit pattern. Lesions of dysplasia (e,f,g). e (31.5×): low-grade dysplasia. f (31.3×): high-grade dysplasia. g: endoscopically visible low-grade dysplasia with central ulcer. Vessel disorganization (red arrows) and glandular disorganization (green arrows) are observed. Glandular atrophy (yellow arrows) surrounds the lesion. Lesions of early gastric cancer (h,i). h (3.8×): early gastric cancer (intramucosal, red arrow). i: early gastric cancer centered on an ulcer. Absent glands with complete architectural loss of the mucosal and vascular pattern. (B) Plasma biomarkers identified at each step of the gastric cancer cascade. * detailed in Table 1.