Table 1.
Summary of potential biomarkers for gastric cancer screening and early diagnosis in blood.
| Sample | Type | Biomarker | Patients | AUC (95% CI) | Sensitivity (%) | Specificity (%) | Ref. |
|---|---|---|---|---|---|---|---|
| Blood Biomarkers | |||||||
| Blood (serum) |
DNA | Circulating free DNA | 216 patients (92 healthy patients and 124 primary gastric cancer patients) | 0.94 (0.91–0.97) | 78.96 | 91.81 | [15] |
| Blood (plasma) | DNA | Circulating free DNA | 132 patients (34 healthy patients, 34 GC patients, and 64 benign gastric patients) | 0.99 | 96.67 | 94.11 | [16] |
| Blood (plasma) | DNA + protein | Mutations in circulating free DNA (16 genes + 8 proteins) | 1817 patients (812 healthy patients, 68 GC patients, 209 breast cancer patients, 388 colorectal cancer patients, 45 esophagus cancer patients, 44 liver cancer patients, 104 lung cancer patients, 54 ovary cancer patients, and 93 pancreatic cancer) | 0.91 (0.90–0.92) | 70.00 for GC | 99.00 | [18] |
| Blood (plasma) | DNA | Methylated RUNX3 | 111 patients (61 healthy patients and 50 GC patients) | 0.69 | 50.00 | 80.30 | [20] |
| Blood (plasma) | DNA | Methylated SFRP2 | 236 patients (50 healthy patients, 92 GC patients, 16 intestinal metaplasia patients, 26 gastric fundic gland polyp patients, 13 small adenoma patients, and 39 hyperplastic polyp patients) | 0.78 (0.71–0.86) | 60.90 | 86.0 | [21] |
| Blood (plasma) | DNA | Methylated RPRML | 50 patients (25 healthy patients and 25 GC patients) | 0.73 (0.58–0.87) | 56.00 | 88.00 | [22] |
| Blood | DNA | mtDNA | 276 patients (48 healthy patients, 74 patients with non-atrophic gastritis, 31 patients with intestinal metaplasia, and 123 GC patients) | - | 47.00 | 80.00 | [24] |
| Blood (plasma) | miRNA | hsa-miR-320a | 3408 patients (3174 healthy patients and 234 GC patients) | 0.96–1.00 | 99.10–100.00 | 88.8–100.00 | [26] |
| Blood (plasma) | miRNA | hsa-miR-1260b | 3408 patients (3174 healthy patients and 234 GC patients) | 0.97–1.00 | 97.40–98.00 | 89.60–100.00 | [26] |
| Blood (plasma) | miRNA | hsa-miR-6515-5p | 3408 patients (3174 healthy patients and 234 GC patients) | 0.95–0.99 | 92.20–98.00 | 88.70–92.70 | [26] |
| Blood (serum) | miRNA | Exosomal miR-590-5p | 218 patients (50 healthy patients and 168 GC patients) | 0.81 | 63.70 | 86.00 | [29] |
| Blood (plasma) | miRNA | Exosomal miR-1246 | 165 patients (50 healthy patients, 30 patients with benign gastric disease, and 85 GC patients) | 0.91 (0.86–0.96) | 82.30 | 86.00 | [30] |
| Blood (serum) | miRNA | miR-101-3p | 197 patients (50 healthy patients, 86 GC patients and 61 atrophic gastritis patients) | 0.88 | 72.09 | 86.49 | [33] |
| Blood (plasma) | miRNA | miR-376c | 173 patients (108 healthy patients and 65 GC patients) | 0.77 | 71.00 | 78.00 | [31] |
| Blood (plasma) | miRNA | miR-21 | 100 patients (50 healthy patients and 50 GC patients) | 0.91 (0.87–0.97) | 88.40 | 79.60 | [32] |
| Blood (plasma) | miRNA panel | Pre-Cancer Screening Model (age, miR-19a-3p and miR-483-5p) | 180 patients (70 gastritis subjects, 20 low-grade intraepithelial neoplasia, 34 high-grade intraepithelial neoplasia, and 56 early GC) | Early GC and prec. lesions: 0.84 (0.77–0.90) | Early GC and prec. lesions: 87.70 | Early GC and prec. lesions: 62.80 | [34] |
| Blood (plasma) | miRNA panel | miR-16, miR-25, miR-92a, miR-451 and miR-486-5p | 320 patients (160 healthy patients, 124 non cardia GC patients, and 36 cardia GC patients) | Non-cardia GC: 0.81 | Non-cardia GC: 72.90 | Non-cardia GC: 89.20 | [35] |
| Blood (serum) | miRNA panel | 12 miRNA panel | 5248 patients (4803 healthy patients and 445 GC) | 0.85 (0.81–0.88) | 87.00 | 68.40 | [36] |
| Blood (serum) | miRNA panel + other factors | miRNA panel + age + H. pylori serology + pepsinogen I/II ratio | 5248 patients (4803 healthy patients and 445 GC) | 0.88 | 87.00 | 69.40 | [36] |
| Blood (plasma) | circRNA | hsa_circ_0000520 | 62 patients (17 healthy patients and 45 GC) | 0.90 | 82.35 | 84.44 | [37] |
| Blood (plasma) | circRNA | Exosomal circ_0065149 | 80 patients (41 healthy patients and 39 early GC) | 0.64 | 48.70 | 90.20 | [38] |
| Blood (plasma) | circRNA | circ_0000745 | 120 patients (60 healthy patients and 60 GC patients) | 0.68 | 85.50 | 45.00 | [39] |
| Blood (plasma) | circRNA | circ_0000745 + CEA | 120 patients (60 healthy patients and 60 GC patients) | 0.78 | 80.00 | 63.30 | [39] |
| Blood (plasma) | circRNA | circPTPN22 | 294 patients (104 healthy patients, 120 plasma of GC patients, and 70 gastritis patients) | 0.857 (0.808–0.907) | 78.00 | 84.00 | [40] |
| Blood (plasma) | circRNA + antigens | circPTPN22 + CEA + CA199 | 294 patients (104 healthy patients, 120 plasma of GC patients, and 70 gastritis patients) | 0.89 | 83.00 | 87.00 | [40] |
| Blood (serum) | lncRNA | multi-lncRNA diagnostic panel (CUDR, LSINCT-5 and PTENP1) | 231 patients (124 healthy patients, 110 GC patients, 9 early-stage GC, 21 later-stage GC, and 15 gastric peptic ulcer patients without GC) | GC:0.83 Early-GC: 0.83 Later-GC: 0.83 |
GC: 81.80 Early-GC: 77.80 Later-GC: 85.70 |
GC: 85.20 Early-stage: 97.00 Later-stage: 84.80 |
[41] |
| Blood (plasma) | lncRNA | TINCR, CCAT2, AOC4P, BANCR and LINC00857 | 321 patients (110 healthy patients, 162 GC patients, 28 prec. Patients, and 21 GIST) | GC: 0.90 (0.86–0.95) Prec: 0.82 (0.71–0.92) GIST: 0.80 (0.68–0.91 |
GC: 0.81 (0.71–0.89) Prec: 0.68 (0.50–0.82) GIST: 0.68 (0.50–0.82) |
GC: 0.86 (0.77–0.93) Prec: 0.89 (0.72–0.98) GIST: 0.86 (0.64–0.97) |
[42] |
| Blood (plasma) | lncRNA | Exosomal LINC00152 | 191 patients (81 healthy patients, 79 GC patients, and 31 gastric epithelial dysplasia patients) | 0.66 (0.57–0.74) | 48.10 | 85.20 | [43] |
| Blood (plasma) | lncRNA | Exosomal lncUEGC1 | 144 patients (65 healthy patients, 18 CAG, and 61 stage I/II GC patients) | 0.88 | - | - | [44] |
| Blood (serum) | lncRNA | Exosomal lncRNA HOTTIP | 246 patients (120 healthy patients and 126 GC patients) | 0.83 | 69.80 | 85.00 | [45] |
| Blood (serum) | lncRNA | Exosomal lncRNA HOTTIP + CEA + CA19-19 + CA72-4 | 246 patients (120 healthy patients and 126 GC patients) | 0.87 | - | - | [45] |
| Blood (plasma) | Protein | Protein signature (ATP5B-ATP5O-NDUFB4-NDUFB8) | 71 patients (34 healthy patients and 37 GC patients) | 0.79 | - | - | [47] |
| Blood (serum) | Protein panel | Protein signature (VEGF, ADAM8, IgG to H. pylori status, serum pepsinogen I, and pepsinogen II) | 523 patients (238 healthy patients and 285 GC patients) | 0.85 (0.77–0.93) | 88.60 | 83.20 | [48] |
| Blood (serum) | Protein | SLC6A3 | 220 patients (56 healthy patients, 113 GC patients, and 51 patients with polyps) | 0.72 (0.64–0.80) | 55.75 | 78.57 | [49] |
| Blood (serum) | Protein panel | SLC6A3, CEA and CA19-9 | 220 patients (56 healthy patients, 113 GC patients, and 51 patients with polyps) | 0.82 (0.75–0.88) | 84.07 | 58.93 | [49] |
| Blood (serum) | Protein | anti-GRP78 autoantibody | 866 patients (433 healthy patients and 433 GC patients) | 0.67 | 35.30 | - | [46] |
| Blood (plasma) | Protein | Q8NBP7 | 30 patients (15 healthy controls and 15 early GC) | 0.702 | 60.0 | 80.0 | [50] |
| Blood (plasma) | Protein | P00441 | 30 patients (15 healthy controls and 15 early GC) | 0.707 | 93.3 | 46.7 | [50] |
| Blood (plasma) | Protein | Q86UD1 | 30 patients (15 healthy controls and 15 early GC) | 0.711 | 46.7 | 100 | [50] |
| Blood (plasma) | Protein | A0A2R8Y7X9 | 30 patients (15 healthy controls and 15 early GC) | 0.796 | 80.0 | 86.7 | [50] |
| Blood (plasma) | Protein | P62979 | 30 patients (15 healthy controls and 15 early GC) | 0.724 | 86.7 | 66.7 | [50] |
| Blood (plasma) | Protein | A0A0G2JMC9 | 30 patients (15 healthy controls and 15 early GC) | 0.747 | 60.0 | 93.3 | [50] |
| Blood (plasma) | Protein | P08493 | 30 patients (15 healthy controls and 15 early GC) | 0.813 | 73.3 | 80.0 | [50] |
| Blood (plasma) | Protein | P16157 | 30 patients (15 healthy controls and 15 early GC) | 0.653 | 46.7 | 86.7 | [50] |
| Blood (plasma) | Protein | A0A087WTY6 | 30 patients (15 healthy controls and 15 early GC) | 0.64 | 80.0 | 53.3 | [50] |
| Blood (plasma) | Protein | P14207 | 30 patients (15 healthy controls and 15 early GC) | 0.689 | 60.0 | 80.0 | [50] |
| Blood (plasma) | Protein | Q9H939 | 30 patients (15 healthy controls and 15 early GC) | 0.573 | 73.3 | 53.3 | [50] |
| Blood (plasma) | Protein panel | 11 protein panel | 30 patients (15 healthy controls and 15 early GC) | 0.711 | 66.7 | 86.7 | [50] |
| Blood (serum) | Protein | PGI | 72 patients (35 healthy controls, 34 CAG and 3 GC) | 0.659 | 66.7 | 85.3 | [51] |
| Blood (serum) | Protein | PGI:II ratio | 72 patients (35 healthy controls, 34 CAG and 3 GC) | 0.902 | 83.3 | 77.9 | [51] |
| Blood (serum) | Protein | TFF3 | 567 patients (325 healthy controls and 242 GC patients) | 0.890 | 80.9 | 81.0 | [53] |
| Blood (plasma) | Protein | TFF3 | 86 patients (44 healthy controls and 42 stage I GC patients) | 0.703 | 83.3 | 54.5 | [54] |
| Blood (serum) | Protein | Hs-CRP + PGI:II ratio | 378 patients (69 healthy controls, 47 CAG, 75 IM, 41 early GC, 43, AGC, and 87 metastasis GC) | - | AGC: 67.0 IM: 67.0 |
AGC: 85.0 IM: 72.0 | [57] |
| Blood (serum) | Protein | Hs-CRP | 378 patients (69 healthy controls, 47 CAG, 75 IM, 41 early GC, 43, AGC, and 87 metastasis GC) | - | AGC: 67.0 | AGC: 85.0 | [57] |
GC, gastric cancer; CAG, chronic atrophic gastritis; IM, intestinal metaplasia; AGC, locally advanced gastric cancer; prec, precancerous; GIST, gastrointestinal stromal tumor; AUC, area under the curve; Ref, reference; -, no data available.