Table 4.
Clinical characteristics of the included studies for the diagnosis of GC.
| Study | Study Format/Nationality | Diagnosis | Number of Patients | Number of Control | Cut-off Value | Detection Method of sPGA | Age (Years, Mean ± SD) | Gender (M/F) | Smoking | H. pylori | TP | FP | FN | TN |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chang et al. (1992) [34] | Case–control/Taiwan | GC | 192 (175 AGC) | 70 | PG I ≤70 ng/mL | RIA | GC: 64.6 ± 8.3/control: 51.2 ± 11.2, range: 32–85 | 235/27 | 112/262 (42.7%) | 124 | 12 | 68 | 58 | |
| Hattori et al. (1995) [35] | Cohort/Japan (follow-up duration: 1 year) | GC (100% adenocarcinoma; 7 undifferentiated- and 11 differentiated-type histology) (sPGA positive subjects were screened by endoscopy) | 18/4876 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | RIA | Range: 40–61 | 4761/115 | 15 | 1243 | 3 | 3615 | |||
| Kodoi et al. (1995) [36] | Case–control/Japan | GC | 269 (127 EGCs, 142 AGCs/167 differentiated-, 102 undifferentiated-type histology) | 1345 (sex, age matched) | PG I<70 ng/mL and PG I/PG II ratio <3 | RIA | GC: median 65 (range: 24–80) | 1080/534 | 162 | 543 | 107 | 802 | ||
| Watanabe et al. (1997) [37] | Nested case–control/Japan | GC | 45 | 225 (sex-, age-, and address-matched control) | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | RIA | 156/114 | 211/270 | 34 | 99 | 11 | 126 | ||
| Kitahara et al. (1999) [38] | Cross-sectional /Japan | GC | 13/5113 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | RIA | Mean 52.5 | 2456/2657 | 11 | 1352 | 2 | 3748 | |||
| PG I/PG II ratio ≤3 | 11 | 1673 | 2 | 3427 | ||||||||||
| Dinis-Ribeiro et al. (2004) [21] | Cross-sectional /Portugal | LGD | 23/136 | PG I/PG II ratio ≤3 | ELISA | Median 61 (range: 26–75) | 50/86 | 16 | 39 | 7 | 74 | |||
| Ohata et al. (2004) [39] | Cohort/Japan (follow-up duration: mean 7.7 ± 0.9 year) | GC (Those with positive double-contrast barium X-ray and/or a positive PG test were further examined by endoscopy) | 45/4655 | PG I/PG II ratio <3 | RIA | 49.5 ± 4.6 | 100% male | 3657/4655 (78.6%) | 27 | 1585 | 18 | 3025 | ||
| Kim et al. (2005) [40] | Case–control/Korea | GC | 13 | 30 | PG I<70 ng/mL and PG I/PG II ratio <3 | RIA | Normal endoscopy group: mean 33.4, atrophic gastritis: 47.8, GC: 57 | 9 | 7 | 4 | 23 | |||
| Watabe et al. (2005) [41] | Cohort/Japan (follow-up duration: mean 4.7 ± 1.7 years) | GC | 43 (34 intestinal- and 9 diffuse-type histology)/6983 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | RIA | 48.9 ± 8.5 | 4782/2201 | 3216/6983 (46.1%) in total, 29/43 (67.4%) in GC | 30 | 1495 | 13 | 5445 | ||
| Oishi et al. (2006) [42] | Cohort/Japan (follow-up duration: 14 years) | GC | 89/2446 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | RIA | Mean 57 in male and 59 in female | 1016/1430 | 80.2% in male and 8.2% in female | 1745/2446 (71.3%) in total and 78/89 (87.6%) in GC | 53 | 661 | 36 | 1696 | |
| Sasazuki et al. (2006) [43] | Nested case-control/Japan | GC (299 differentiated- and 159 undifferentiated-type histology) | 511 | 511 (matched for gender, age, study area, blood donation date, fasting time at blood donation) | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | EIA | 57.4 ± 0.32 | Male: 66.8% | GC: 35.7%, control: 30.3% | 419 | 295 | 92 | 216 | |
| Sugiu et al. (2006) [44] | Case–control/Japan | GC | 27 | 65 | PG I/PG II ratio ≤3 | RIA | Mean 57.9 (range: 15–88) | 54/38 | 100% | 23 | 32 | 4 | 33 | |
| Kang et al. (2008) [45] | Case–control/Korea | GC | 380 | 626 | PG I ≤70 ng/m | L-TIA | 57.6 ± 13.2 | 585/421 | 788/1006 (78.3%) | 275 | 500 | 105 | 126 | |
| GC | 380 | 626 | PG I/PG II ratio ≤3 | 225 | 244 | 155 | 382 | |||||||
| Dysplasia | 107 | 899 | PG I ≤70 ng/m | 88 | 717 | 19 | 182 | |||||||
| Dysplasia | 107 | 899 | PG I/PG II ratio ≤3 | 66 | 351 | 41 | 548 | |||||||
| Yanaoka et al. (2008) [46] | Cohort/Japan (follow-up duration: mean 9.7 ± 0.9 years ) | GC (Those with positive double-contrast barium X-ray and/or a positive PG test were further examined by endoscopy) | 63/5209 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | RIA | 49.2 ± 4.7 | 100% male | 37 | 1370 | 26 | 3776 | |||
| Yanaoka et al. (2008) [47] | Cohort/Japan (follow-up duration: mean 9.7 ± 0.9 years ) | GC (Those with positive double-contrast barium X-ray and/or a positive PG test were further examined by endoscopy) | 63/5209 | PG I/PG II ratio ≤3 | RIA | 49.2 ± 4.7 | 100% male | 3656/5209 | 43 | 1713 | 20 | 3433 | ||
| Miki et al. (2009) [48] | Cohort/Japan (follow-up duration: 15 year) | GC including intramucosal cancers (Those with a positive PG test and those with a negative PG test took endoscopy every 2 and 5 years, respectively) | 125 (28 EGCs, 72 intramucosal cancers, 25 AGCs)/13789 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | RIA or L-TIA | Mean 48.7 | Initial enrollment: 101,892 (85,578/16,314) | 110 | 9026 | 15 | 4638 | |||
| Mizuno et al. (2009) [49] | Cohort/Japan (follow-up duration: 1 year) | GC (PG I level of ≤30 ng/mL and a PG I/PG II ratio of ≤2.0 or those with abnormal X-ray findings were advised to undergo endoscopy) | 19/12120 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | CLIA | Male: median 50 (range: 15–84), Female: median 49 (range: 22–84) | 7590/4530 | 13 | 1743 | 6 | 10,358 | |||
| Yamaji et al. (2009) [50] | Cohort/Japan (follow-up duration: mean 4.79 years) | GC | 37/6158 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | ELISA | Mean 49 | 4259/1899 | 2177/6158 (current or past smoker) | 2901/6158 | 27 | 1333 | 10 | 4788 | |
| Yanaoka et al. (2009) [51] | Cohort/Japan (follow-up duration: mean 9.3 ± 0.7 years) | GC (Those with positive double-contrast barium X-ray and/or a positive PG test were further examined by endoscopy) | 60 (40 intestinal- and 20 diffuse-type histology)/4129 (3,656 with persistent H. pylori infection and 473 with successful H. pylori eradication) | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | RIA | 49.8 ± 4.6 in H. pylori infection group, 49.6 ± 5.5 in eradication group | 100% male | 57.1% in H. pylori infection group, 55.4% in eradication group | 100% infected | 28 | 1050 | 32 | 3019 | |
| Agkoc et al. (2010) [26] | Case–control/Turkey | GC | 50 | 90 | PG I/PG II ratio <3 | RIA | GC: 65.42 ± 10.28 (range: 38–83) | 78/62 | 42 | 9 | 8 | 81 | ||
| Kwak et al. (2010) [52] | Cross-sectional/Korea | GC | 460 | 460 | PG I/PG II ratio ≤3 | L-TIA | Mean 57.9 | 528/392 | 765 (83.2%) | 244 | 136 | 216 | 324 | |
| Mizun et al. (2010) [53] | Cohort/Japan (follow-up duration: median 9.3 years) | GC | 61/2859 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | RIA | 55–74 category is most prevalent | 1011/1848 | 2148/2859 | 44 | 1079 | 17 | 1719 | ||
| Aikou et al. (2011) [54] | Case–control/Japan | GC | 183 (107 AGCs, 76 EGCs; 86 differentiated- and 97 undifferentiated-type EGCs) | 269 | PG I<70 ng/mL and PG I/PG II ratio <3 | ELISA | GC: 66.0 ± 10.7/control: 50.1 ± 9.9 | 362/90 | GC: 62.3%, control: 34.9% | 82 | 34 | 101 | 235 | |
| Chang et al. (2011) [55] | Case–control/Korea | Gastric neoplasms | 297 (61 LGDs, 21 HGDs, 84 EGCs, 131 AGCs) | 293 | PG I/PG II ratio ≤3 | L-TIA | LGD: 60.2 ± 9.5, HGD: 63.1 ± 8.6, EGC: 59.8 ± 9.2, AGC: 61.6 ± 12.6, control: 50.7 ± 13.6 | 368/222 | Gastric neoplasms: 22.8–51.9%, control: 24.2% | Gastric neoplasms: 60.7–81%, control: 58% | 184 | 89 | 113 | 204 |
| Kaise et al. (2011) [56] | Case–control/Japan | GC | 192 | 1254 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | CLIA | GC: 64.3 ± 9.7/control: 52.3 ± 12.4 | GC: 5:1, control: 1.2:1 | GC: 63%, control: 38.2% | GC: 83.9%, control: 30.1% | 129 | 229 | 63 | 1025 |
| Kikuchi et al. (2011) [57] | Case–control/Japan | EGC | 122 (114 well- to moderate-differentiated EGCs and 8 poorly-differentiated EGCs) | 178 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | CLIA | GC: 68.2 ± 9.7/control: 56.2 ± 14.9 | 187/113 | GC: 100/122 (82%), control: 109/178 (61.2%) | 95 | 68 | 27 | 110 | |
| PG I ≤70 ng/mL | 114 | 148 | 8 | 30 | ||||||||||
| PG I/PG II ratio ≤3 | 100 | 83 | 22 | 95 | ||||||||||
| Ito et al. (2012) [58] | Case–control/Japan | Diffuse-type EGC | 42 | 511 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | RIA | GC: mean 57.2 in male, 59.1 in female. Control: mean 58.5 | 305/248 | 387/553 | 20 | 191 | 22 | 320 | |
| Lomba-Viana et al. (2012) [59] | Cohort/Portugal (follow-up duration: 3–5 year) | GC | 6 (5 intestinal- and 1 diffuse-type histology/3 EGCs and 3 AGCs)/514 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | ELISA | Median 60 (range: 40–79) | 76/438 | 165/514 (32.1%) | 6 | 268 | 3 | 237 | ||
| Zhang et al. (2012) [60] | Cohort/China (follow-up duration: 14 years) | GC | 26/1501 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | RIA | 45.29 ± 12.18 | 554/947 | 995/1501 (66.3%) | 9 | 158 | 17 | 1317 | ||
| Yakut et al. (2013) [27] | Case–control/Turkey | Dysplasia | 37 | 125 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | ELISA | 57.52 ± 11.16 | 75/87 | 24 (14.8%) | 98/162 (60.5%) | 13 | 38 | 24 | 87 |
| PG I ≤70 ng/mL | 13 | 37 | 24 | 88 | ||||||||||
| PG I/PG II ratio ≤3 | 8 | 30 | 29 | 95 | ||||||||||
| Choi et al. (2014) [61] | Case–control/Korea | Gastric neoplasms | 17 | 3311 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | L-TIA | Mean 49.8–59.0 | 1979/1349 | 9 | 438 | 8 | 2873 | ||
| Huang et al. (2014) [62] | Nested case-control/China | GC | 72 | 37 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | CLIA | GC: 61.7 ± 1.4, control: 56.7 ± 2.8 | GC: 1.23:1. Control: 1.31:1 | GC: 66.7%, control: 48% | 27 | 7 | 45 | 30 | |
| Yoshida et al. (2014) [63] | Cohort/Japan (follow-up duration: mean 11.6 ± 4.3 years) | GC (those with positive double-contrast barium X-ray and/or a positive PG test were further examined by endoscopy) | 87/4655 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | RIA | 49.5 ± 4.6 | 100% male | 59.3% | 3657/4655 | 48 | 1314 | 39 | 3254 | |
| Zhang et al. (2014) [64] | Case–control/China | GC | 82 (69 AGCs, 13 EGCs) | 142 | PG I ≤70 ng/mL | ELISA | Patients with gastrointestinal diseases: 52.3 ± 12.3 (range 19–80), control: 52.4 ± 15.1 (range 29–77) | 163/85 | 85.4% in patients with GC, 74.4% in control | 56 | 25 | 26 | 117 | |
| PG I/PG II ratio ≤3 | 21 | 2 | 61 | 140 | ||||||||||
| Eybpoosh et al. (2015) [65] | Cross-sectional/Iran | GC | 578 (62 EGCs, 516 AGCs/315 intestinal-, 203 diffuse-, 69 mixed-type histology/274 undifferentiated-, 304 differentiated-type histology) | 763 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | ELISA | 750/591 | 399/1341 | 100 | 44 | 478 | 719 | ||
| PG I ≤70 ng/mL | 133 | 234 | 445 | 529 | ||||||||||
| PG I/PG II ratio ≤3 | 32 | 34 | 546 | 729 | ||||||||||
| Ikeda et al. (2016) [66] | Cohort/Japan (follow-up: at least 20 years) | GC | 123/2446 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | RIA | 58.3 ± 11.4 | 1016/1430 | 24.6% | 1761/2446 | 70 | 644 | 53 | 1679 | |
| Cho et al. (2017) [67] | Case–control/Korea | Gastric neoplasms | 87 (19 LGDs, 16 HGDs, 40 EGCs, 12 AGCs) | 311 | PG I/PG II ratio ≤3 | L-TIA | 48.2 ± 16.6 | 170/228 | 209/398 (52.5%) (46% with neoplasm vs. 75.9% without neoplasm) | 59 | 62 | 28 | 249 | |
| Hamashima et al. (2017) [68] | Nested case-control/Japan | GC | 497 | 497 (matched for sex, age, blood donation date, and fasting time at blood donation) | PG I/PG II ratio ≤3 | EIA | 57.5 ± 7.2 | Male: 66.4% | 432 | 299 | 65 | 198 | ||
| Tu et al. (2017) [69] | Cohort/China (follow-up duration: median 11.6 years) | GC | 86/12018 | PG I ≤70 ng/mL | ELISA | GC: 59.0 ± 10.6/GC-free: 49.6 ± 10.7 | 82.6% male in GC/45.1% male in GC-free | 39% in GC/36.4% in GC-free | 27 | 3642 | 59 | 8290 | ||
| PG I/PG II ratio <3 | 15 | 728 | 71 | 11204 | ||||||||||
| Castro et al. (2018) [70] | Cohort/Portugal (follow-up duration: median 6.5 years for sPGA (+)/7.5 years for sPGA (–) | GC (100% adenocarcinoma) | 26/5913 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | ELISA | Range: 40–74 | 2257/3656 | 9 | 216 | 17 | 5671 | |||
| Kwak et al. (2018) [71] | Cohort/Korea (follow-up duration: mean 5.6 years) | GC | 15/3297 | PG I ≤70 ng/mL and PG I/PG II ratio ≤3 | L-TIA | 51.3 ± 9.4 | 2326/971 | 2020/3297 | 7 | 567 | 8 | 2715 | ||
| Gastric neoplasms | 29/3297 | 12 | 562 | 17 | 2706 | |||||||||
| Lee et al. (2018) [72] | Case–control/Korea | EGC | 30 | 30 | PG I<70 ng/mL and PG I/PG II ratio <3 | L-TIA | 59.5 ± 10.7 (patients with EGC) vs. 66.6 ± 12.0 (control) | 36/24 | 10 | 2 | 20 | 28 | ||
| Sjomina et al. (2018) [73] | Cross-sectional/Latvia | GC | 2 | 257 | PG I<70 ng/mL and PG I/PG II ratio <3 | L-TIA | 56.5 ± 12.5 | 82/177 | 177 (66%) | 1 | 160 | 1 | 97 | |
| Gastric dysplasia | 21 | 238 | 17 | 144 | 4 | 94 |
sPGA, serum pepsinogen assay; M, male; F, female; SD, standard deviation; TP, true positive; FP, false positive; FN, false negative; TN, true negative; GC, gastric cancer; EGC, early gastric cancer; AGC, advanced gastric cancer; LGD, low grade dysplasia; HGD, high grade dysplasia; PG, pepsinogen; RIA, radioimmunoassay; EIA, enzyme immunoassay; CLIA, chemiluminescent immunoassay; ELISA, enzyme-linked immunosorbent assay; L-TIA, latex-enhanced turbidimetric immunoassay.