Copyright
©The Author(s) 2018.
World J Gastroenterol. Feb 7, 2018; 24(5): 631-640
Published online Feb 7, 2018. doi: 10.3748/wjg.v24.i5.631
Published online Feb 7, 2018. doi: 10.3748/wjg.v24.i5.631
Table 1 Patient demographics and disease characteristics n (%)
| Clinicopathological feature | PIK3CA | P value | TP53 | P value | Both PIK3CA and TP53 wild-type | Both PIK3CA and TP53 mutation | Others | P value | ||
| Wild-type | Mutation | Wild-type | Mutation | |||||||
| Age (yr) | ||||||||||
| < 60 | 52 (26.80) | 29 (23.97) | 31 (28.18) | 50 (24.39) | 26 (31.33) | 22 (28.57) | 33 (21.29) | |||
| 60-70 | 47 (24.23) | 33 (27.27) | 28 (25.45) | 52 (25.37) | 20 (24.10) | 18 (23.38) | 42 (27.10) | |||
| ≥ 70 | 95 (48.97) | 59 (48.76) | 0.776 | 51 (46.36) | 103 (50.24) | 0.733 | 37 (44.58) | 37 (48.05) | 80 (51.61) | 0.500 |
| Sex | ||||||||||
| Male | 107 (55.15) | 73 (60.33) | 67 (60.91) | 113 (55.12) | 47 (56.63) | 45 (58.44) | 88 (56.77) | |||
| Female | 87 (44.85) | 48 (39.67) | 0.367 | 43 (39.09) | 92 (44.88) | 0.322 | 36 (43.37) | 32 (41.56) | 67 (43.23) | 0.965 |
| Tumor location | ||||||||||
| Rectum | 109 (56.19) | 53 (43.80) | 53 (48.18) | 109 (53.17) | 48 (57.83) | 41 (53.25) | 73 (47.10) | |||
| Proximal | 39 (20.10) | 39 (32.23) | 32 (29.09) | 46 (22.44) | 17 (20.48) | 19 (24.68) | 42 (27.10) | |||
| Distal | 46 (23.71) | 29 (23.97) | 0.036 | 25 (22.73) | 50 (24.39) | 0.426 | 18 (21.69) | 17 (22.08) | 40 (25.81) | 0.601 |
| Stage T | ||||||||||
| T1-T2 | 34 (17.53) | 26 (21.49) | 20 (18.18) | 40 (19.51) | 15 (18.07) | 16 (20.78) | 29 (18.71) | |||
| T3 | 38 (19.59) | 19 (15.70) | 21 (19.09) | 36 (17.56) | 17 (20.48) | 11 (14.29) | 29 (18.71) | |||
| T4 | 122 (62.89) | 76 (62.81) | 0.539 | 69 (62.73) | 129 (62.93) | 0.923 | 51 (61.45) | 50 (64.94) | 97 (62.58) | 0.884 |
| Stage N | ||||||||||
| N0 | 118 (60.82) | 70 (57.85) | 68 (61.82) | 120 (58.54) | 53 (63.86) | 45 (58.44) | 90 (58.06) | |||
| N1 | 55 (28.35) | 35 (28.93) | 28 (25.45) | 62 (30.24) | 20 (24.10) | 23 (29.87) | 47 (30.32) | |||
| N2 | 21 (10.82) | 16 (13.22) | 0.785 | 14 (12.73) | 23 (11.22) | 0.656 | 10 (12.05) | 9 (11.69) | 18 (11.61) | 0.889 |
| Stage | ||||||||||
| I | 23 (11.86) | 23 (19.01) | 16 (14.55) | 30 (14.63) | 12 (14.46) | 14 (18.18) | 20 (12.90) | |||
| II | 86 (44.33) | 42 (34.71) | 47 (42.73) | 81 (39.51) | 37 (44.58) | 28 (36.36) | 63 (40.65) | |||
| III | 70 (36.08) | 43 (35.54) | 38 (34.55) | 75 (36.59) | 27 (32.53) | 26 (33.77) | 60 (38.71) | |||
| IV | 15 (7.73) | 13 (10.74) | 0.166 | 9 (8.18) | 19 (9.27) | 0.948 | 7 (8.43) | 9 (11.69) | 12 (7.74) | 0.774 |
Table 2 Top ten mutations of PIK3CA and TP53 in this study
| PIK3CA | n (%) | TP53 | n (%) |
| Glu545Lys | 16 (5.1) | Arg175His | 16 (5.1) |
| Glu542Lys | 7 (2.2) | Arg282Trp | 11 (3.5) |
| Val105Ile | 6 (1.9) | Gly245Ser | 9 (2.9) |
| Met1004Ile | 6 (1.9) | Arg248Gln | 9 (2.9) |
| His1047Arg | 6 (1.9) | Arg273His | 8 (2.5) |
| Glu218Lys | 6 (1.9) | Arg273Cys | 7 (2.2) |
| Trp552Ter | 5 (1.6) | Arg248Trp | 7 (2.2) |
| Ser438Phe | 5 (1.6) | Ser260Phe | 6 (1.9) |
| Pro835Leu | 5 (1.6) | Glu358Lys | 6 (1.9) |
| Asp1029Asn | 5 (1.6) | Pro153Ser | 5 (1.6) |
Table 3 Univariate and multivariate analyses (Cox proportional hazards model) of OS for patients with stage II/III CRC treated with 5-FU-based chemotherapy according to PIK3CA and/or TP53 mutation status n (%)
| Alive | Dead | Univariate HR (95%CI) | P value | Multivariate HR (95%CI) | P value | |
| PIK3CA | ||||||
| Wild-type | 114 (73.08) | 42 (26.92) | 1 (Ref.) | 1 (Ref.) | ||
| Occasional | 5 (55.56) | 4 (44.44) | 1.93 (0.69-5.39) | 0.208 | 1.40 (0.49-4.05) | 0.530 |
| Recurrent | 48 (63.16) | 28 (36.84) | 1.50 (0.93-2.42) | 0.096 | 1.29 (0.79-2.11) | 0.314 |
| TP53 | ||||||
| Wild-type | 63 (74.12) | 22 (25.88) | 1 (Ref.) | 1 (Ref.) | ||
| Occasional | 32 (80.00) | 8 (20.00) | 0.80 (0.35-1.79) | 0.583 | 0.84 (0.37-1.94) | 0.687 |
| Recurrent | 72 (62.07) | 44 (37.93) | 1.65 (0.99-2.76) | 0.055 | 1.68 (0.98-2.87) | 0.057 |
| PIK3CA and TP53 | ||||||
| Both PIK3CA and TP53 Wild-type | 49 (76.56) | 15 (23.44) | 1 (Ref.) | 1 (Ref.) | ||
| Both PIK3CA and TP53 Mutation | 31 (57.41) | 23 (42.59) | 2.21 (1.15-4.24) | 0.017 | 2.02 (1.04-3.91) | 0.037 |
| Others | 87 (70.73) | 36 (29.27) | 1.31 (0.72-2.40) | 0.376 | 1.16 (0.63-2.16) | 0.629 |
Table 4 Association of PIK3CA functional domain mutations with overall survival in stage II/III CRC patients n (%)
| Domain | Alive | Dead | Multivariate HR (95%CI) | P value |
| Kinase domain | ||||
| Wild-type | 116 (60.42) | 76 (39.58) | 1 (Ref.) | |
| Mutation | 23 (46.94) | 26 (53.06) | 1.56 (1.00-2.44) | 0.052 |
| C2 domain | ||||
| Wild-type | 118 (58.71) | 83 (41.29) | 1 (Ref.) | |
| Mutation | 21 (52.50) | 19 (47.50) | 1.13 (0.68-1.86) | 0.638 |
| Helical domain | ||||
| Wild-type | 110 (59.14) | 76 (40.86) | 1 (Ref.) | |
| Mutation | 29 (52.73) | 26 (47.27) | 1.30 (0.83-2.05) | 0.248 |
| p85 binding domain | ||||
| Wild-type | 127 (57.73) | 93 (42.27) | 1 (Ref.) | |
| Mutation | 12 (57.14) | 9 (42.86) | 1.05 (0.53-2.08) | 0.894 |
| Ras binding domain | ||||
| Wild-type | 123 (58.57) | 87 (41.43) | 1 (Ref.) | |
| Mutation | 16 (51.61) | 15 (48.39) | 1.27 (0.73-2.20) | 0.404 |
- Citation: Li AJ, Li HG, Tang EJ, Wu W, Chen Y, Jiang HH, Lin MB, Yin L. PIK3CA and TP53 mutations predict overall survival of stage II/III colorectal cancer patients. World J Gastroenterol 2018; 24(5): 631-640
- URL: https://www.wjgnet.com/1007-9327/full/v24/i5/631.htm
- DOI: https://dx.doi.org/10.3748/wjg.v24.i5.631