Table 3.
Comparison of clinical performance of single methylation biomarkers for colorectal cancer (CRC) and precancerous lesion detection from representative studies.
| Sample type | Methylation biomarker | Sensitivity | Specificity | Reference | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SP | AA | Stage 0 CRC | Stage I CRC | Stage II CRC | Stage III CRC | Stage IV CRC | Stage 0 to II | All stage CRC | ||||
| Blood | C9orf50 | 50.0% (8/16) | 79.4% (54/68) | 81.8% (18/22) | 85.7% (6/7) | 73.8% (62/84) | 76.1% (86/113) | 90.8% (79/87) | (43) | |||
| KCNQ5 | 87.5% (14/16) | 83.8% (57/68) | 72.7% (16/22) | 100.0% (7/7) | 84.5% (71/84) | 83.2% (94/113) | 95.4% (83/87) | |||||
| Stool | C9orf50 | 25.7% (26/101) | 50.0% (10/20) | 60.0% (3/5) | 90.6% (29/32) | 87.9% (51/58) | 84.7% (50/59) | 85.7% (18/21) | 87.4% (83/95) | 85.9% (170/198) | 95.0% (134/141) | This study |
| KCNQ5 | 36.6% (37/101) | 75.0% (15/20) | 60.0% (3/5) | 84.4% (27/32) | 82.8% (48/58) | 69.5% (41/59) | 66.7% (14/21) | 82.1% (78/95) | 77.3% (153/198) | 91.5% (129/141) | ||
| C9orf50 and KCNQ5 combined | 41.6% (42/101) | 75.0% (15/20) | 80.0% (4/5) | 90.6% (29/32) | 89.7% (52/58) | 88.1% (52/59) | 85.7% (18/21) | 89.5% (85/95) | 88.4% (175/198) | 89.4% (126/141) | ||
| SEPT9 | 66.7% (8/12) | 86.7% (13/15) | 94.4% (17/18) | 78.3% (18/23) | 77.8% (7/9) | 90.1% (30/33) | 83.3% (60/72) | 92.1% (70/76) | (50) | |||
| SEPT9* | 50.0% (6/12) | 100.0% (1/1) | 63.6% (7/11) | 93.3% (14/15) | 77.8% (14/18) | 75.0% (3/4) | 81.5% (22/27) | 79.8% (75/94) | 96.0% (119/124) | (46) | ||
| SDC2* | 50.0% (6/12) | 100.0% (1/1) | 72.7% (8/11) | 100.0% (15/15) | 83.3% (15/18) | 50.0% (2/4) | 88.9% (24/27) | 85.1% (80/94) | 95.1% (118/124) | |||
| SDC2 | 66.7% (2/3) | 100.0% (3/3) | 85.5% (47/55) | 91.4% (64/70) | 89.6% (86/96) | 100.0% (21/21) | 89.1% (114/128) | 90.2% (221/245) | 90.2% (221/245) | (25) | ||
| SFRP2 | 61.8% (21/34) | 87.0% (60/69) | 93.3% (28/30) | (31) | ||||||||
| NDRG4 | 76.2% (66/87) | 89.2% (14/16) | (51) | |||||||||
| COL4A1 | 58.4% (45/77) | 88.8% (71/80) | 88.0% (73/83) | (33) | ||||||||
| COL4A2 | 49.4% (38/77) | 92.5% (74/80) | 91.6% (76/83) | |||||||||
| TLX2 | 54.5% (42/77) | 88.8% (71/80) | 96.4% (80/83) | |||||||||
| ITGA4 | 41.6% (32/77) | 82.5% (66/80) | 96.4% (80/83) | |||||||||
| SPG20 | 80.2% (77/96) | 100.0% (30/30) | (52) | |||||||||
| FBN1 | 91.7% (11/12) | 63.3% (19/30) | 73.3% (22/30) | 66.7% (2/3) | 71.4% (30/42) | 72.0% (54/75) | 93.3% (28/30) | (53) | ||||
| GATA5 | 83.9% (47/56) | 82.5% (33/40) | (32) | |||||||||
| p33ING1b | 62.9% (17/27) | 73.8% (45/61) | 95.0% (19/20) | (54) | ||||||||
| HPP1 | 36.8% (7/19) | 70.0% (7/10) | 71.2% (37/52) | 100.0% (24/24) | (55) | |||||||
| SFRP1 | 43.8% (14/32) | 73.7% (14/19) | 89.7% (35/39) | 90.0% (18/20) | (27) | |||||||
| VIM | 72.5% (29/40) | 86.9% (106/122) | (38) | |||||||||
| Cologuard** | 17.2% (498/2893) | 42.4% (321/757) | 89.7% (26/29) | 100.0% (21/21) | 90.0% (9/10) | 75.0% (3/4) | 94.0% (47/50) | 92.3% (60/65) | 89.8% (4002/4457) | (8) | ||
*Combined results from both training set and validation set. **The results of stool-based multi-target Cologuard test serve as reference. The biomarkers of Cologuard test include BMP3 and NDRG4 methylation, 7 KRAS mutations, and hemoglobin protein.