上海交通大学学报(医学版) ›› 2022, Vol. 42 ›› Issue (8): 1070-1080.doi: 10.3969/j.issn.1674-8115.2022.08.012
• 论著 · 临床研究 • 上一篇
邱佳辉1,2(), 蔡谦谦2, 杨彦2, 程非池2, 裘正军1,2(), 黄陈1,2()
收稿日期:
2022-03-11
接受日期:
2022-07-21
出版日期:
2022-08-28
发布日期:
2022-10-08
通讯作者:
裘正军,黄陈
E-mail:1326880749@qq.com;qiuzjdoctor@sina.com;richard-hc@hotmail.com
作者简介:
邱佳辉(1993—),男,硕士生;电子信箱:1326880749@qq.com。
基金资助:
QIU Jiahui1,2(), CAI Qianqian2, YANG Yan2, CHENG Feichi2, QIU Zhengjun1,2(), HUANG Chen1,2()
Received:
2022-03-11
Accepted:
2022-07-21
Online:
2022-08-28
Published:
2022-10-08
Contact:
QIU Zhengjun,HUANG Chen
E-mail:1326880749@qq.com;qiuzjdoctor@sina.com;richard-hc@hotmail.com
Supported by:
摘要:
目的·探讨肿瘤间质比(tumor-stroma ratio,TSR)、神经浸润(perineural invasion,PNI)、脉管浸润(lymphovascular invasion,LVI)对结直肠癌(colorectal cancer,CRC)患者预后的预测价值。方法·回顾性分析2014年1月—2018年12月在上海交通大学医学院附属第一人民医院确诊为CRC的948例患者资料,按病理高危因素TSR、PNI、LVI分为高风险组(n=81)和低风险组(n=867),经SPSS软件进行1∶1病例匹配后得到高风险组67例。低风险组67例,比较高风险组患者和低风险组患者的总生存时间(overall survival,OS),并使用该课题组106例结直肠癌组织芯片(tissue microarray,TMA)数据进行验证。比较高风险组和低风险组的临床特点,采用Kaplan-Meier法进行生存分析,COX回归模型分析影响预后的因素。结果·与低风险组患者中位OS(31.1个月)相比,高风险组患者中位OS(27.7个月)缩短,预后更差(P=0.000)。经过配对后发现具有神经脉管浸润阳性联合高肿瘤间质比特征对预测CRC预后的价值更大,并且在TMA数据中也得到了验证。结论·神经脉管浸润阳性联合高TSR的CRC是一类预后不良的CRC,可以弥补肿瘤-淋巴结-转移(tumor-node-metastasis,TNM)病理分期系统对预后预测的缺陷,可以用于预估CRC患者术后病情发展及指导治疗。
中图分类号:
邱佳辉, 蔡谦谦, 杨彦, 程非池, 裘正军, 黄陈. 神经脉管浸润联合肿瘤间质比对结直肠癌预后的预测价值[J]. 上海交通大学学报(医学版), 2022, 42(8): 1070-1080.
QIU Jiahui, CAI Qianqian, YANG Yan, CHENG Feichi, QIU Zhengjun, HUANG Chen. Value of combined perineural lymphovascular invasion and tumor-stroma ratio in guiding the prognosis of colorecatal cancer[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(8): 1070-1080.
Indicator | Univariate analysis | Multivariate analysis | |||||
---|---|---|---|---|---|---|---|
HR | 95%CI | P value | HR | 95%CI | P value | ||
Grade | |||||||
Well | ‒ | 1 | ‒ | ||||
Moderate | 2.333 | 0.945‒5.759 | 0.660 | ||||
Poor | 3.824 | 1.451‒10.079 | 0.007* | ||||
T Stage | |||||||
T1 | ‒ | 1 | ‒ | ||||
T2 | 1.897 | 0.240‒14.981 | 0.544 | ||||
T3 | 2.201 | 0.291‒16.676 | 0.445 | ||||
T4 | 6.070 | 0.845‒43.588 | 0.073 | ||||
N Stage | |||||||
N0 | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
N1 | 2.364 | 1.477‒3.784 | 0.000** | 1.742 | 1.065‒2.850 | 0.027* | |
N2 | 5.832 | 3.725‒9.130 | 0.000** | 5.022 | 3.103‒8.128 | 0.000** | |
Tumor location | |||||||
Right | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Left | 0.461 | 0.281‒0.757 | 0.002* | 0.438 | 0.265‒0.723 | 0.001* | |
Rectal | 0.472 | 0.307‒0.725 | 0.001* | 0.472 | 0.304‒0.735 | 0.001* | |
Gender | |||||||
Male | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Female | 0.602 | 0.402‒0.902 | 0.014* | 0.569 | 0.377‒0.858 | 0.007* | |
Tumor size | |||||||
<5 cm | ‒ | 1 | ‒ | ||||
≥5 cm | 1.294 | 0.887‒1.888 | 0.182 | ||||
Age | |||||||
≤67 years | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
>67 years | 3.315 | 2.188‒5.022 | 0.000** | 3.426 | 2.245‒5.227 | 0.000** | |
Risk factor | |||||||
0 | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
1 | 2.122 | 1.156‒3.893 | 0.015* | 2.037 | 1.105‒3.755 | 0.023* | |
2 | 3.742 | 2.013‒6.957 | 0.000** | 2.604 | 1.372‒4.942 | 0.003* | |
3 | 6.074 | 3.065‒12.037 | 0.000** | 3.564 | 1.732‒7.336 | 0.001* |
表1 CRC总体生存率影响因素的单因素和多因素COX分析
Tab 1 Univariate and multivariate COX analysis of influencing factors for overall survival of CRC
Indicator | Univariate analysis | Multivariate analysis | |||||
---|---|---|---|---|---|---|---|
HR | 95%CI | P value | HR | 95%CI | P value | ||
Grade | |||||||
Well | ‒ | 1 | ‒ | ||||
Moderate | 2.333 | 0.945‒5.759 | 0.660 | ||||
Poor | 3.824 | 1.451‒10.079 | 0.007* | ||||
T Stage | |||||||
T1 | ‒ | 1 | ‒ | ||||
T2 | 1.897 | 0.240‒14.981 | 0.544 | ||||
T3 | 2.201 | 0.291‒16.676 | 0.445 | ||||
T4 | 6.070 | 0.845‒43.588 | 0.073 | ||||
N Stage | |||||||
N0 | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
N1 | 2.364 | 1.477‒3.784 | 0.000** | 1.742 | 1.065‒2.850 | 0.027* | |
N2 | 5.832 | 3.725‒9.130 | 0.000** | 5.022 | 3.103‒8.128 | 0.000** | |
Tumor location | |||||||
Right | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Left | 0.461 | 0.281‒0.757 | 0.002* | 0.438 | 0.265‒0.723 | 0.001* | |
Rectal | 0.472 | 0.307‒0.725 | 0.001* | 0.472 | 0.304‒0.735 | 0.001* | |
Gender | |||||||
Male | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Female | 0.602 | 0.402‒0.902 | 0.014* | 0.569 | 0.377‒0.858 | 0.007* | |
Tumor size | |||||||
<5 cm | ‒ | 1 | ‒ | ||||
≥5 cm | 1.294 | 0.887‒1.888 | 0.182 | ||||
Age | |||||||
≤67 years | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
>67 years | 3.315 | 2.188‒5.022 | 0.000** | 3.426 | 2.245‒5.227 | 0.000** | |
Risk factor | |||||||
0 | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
1 | 2.122 | 1.156‒3.893 | 0.015* | 2.037 | 1.105‒3.755 | 0.023* | |
2 | 3.742 | 2.013‒6.957 | 0.000** | 2.604 | 1.372‒4.942 | 0.003* | |
3 | 6.074 | 3.065‒12.037 | 0.000** | 3.564 | 1.732‒7.336 | 0.001* |
图1 CRC的Kaplan-Meier生存分析曲线Note:0 represents negative for LVI, PNI and TSR; 1 represents one positive for LVI, PNI and TSR; 2 represents two positive for LVI, PNI and TSR; 3 represents three positive for LVI, PNI and TSR.
Fig 1 Kaplan-Meier survival analysis for CRC
Indicator | Group | P value | |
---|---|---|---|
Low-risk | High-risk | ||
Gradea | 0.038* | ||
Well | 80 (8.4) | 2 (0.2) | |
Moderate | 667 (70.4) | 62 (6.5) | |
Poor | 120 (12.7) | 17 (1.8) | |
TNM Stagea | 0.000** | ||
Ⅰ | 157 (16.6) | 3 (0.3) | |
Ⅱ | 406 (42.8) | 15 (1.6) | |
Ⅲ | 298 (31.4) | 61 (6.4) | |
Ⅳ | 6 (0.7) | 2 (0.2) | |
T Stagea | 0.014* | ||
T1 | 36 (3.8) | 2 (0.2) | |
T2 | 144 (15.2) | 4 (0.4) | |
T3 | 187 (19.7) | 15 (1.6) | |
T4 | 500 (52.7) | 60 (6.4) | |
N Stagea | 0.000** | ||
N0 | 564 (59.5) | 19 (2.0) | |
N1 | 187 (19.7) | 34 (3.6) | |
N2 | 116 (12.2) | 28 (3.0) | |
Tumor location | 0.729 | ||
Right | 283 (29.9) | 25 (2.6) | |
Left | 232 (24.5) | 25 (2.6) | |
Rectal | 352 (37.1) | 31 (3.3) | |
Gendera | 0.009* | ||
Male | 490 (51.7) | 58 (6.1) | |
Female | 377 (39.8) | 23 (2.4) | |
Tumor sizea | 0.888 | ||
<5 cm | 539 (56.9) | 51 (5.4) | |
≥5 cm | 328 (34.6) | 30 (3.1) | |
Agea | 66.0 (58.0‒74.0) | 65.0 (54.5‒75.5) | 0.538 |
CEAb | 0.051 | ||
Normal | 432 (58.5) | 35 (4.7) | |
Abnormal | 240 (32.5) | 32 (4.3) | |
CA199c | 0.001** | ||
Normal | 540 (71.9) | 42 (5.6) | |
Abnormal | 143 (19.0) | 26 (3.5) | |
CA50d | 0.765 | ||
Normal | 318 (83.2) | 30 (7.9) | |
Abnormal | 30 (7.9) | 4 (1.0) | |
CA125e | 0.398 | ||
Normal | 334 (83.5) | 28 (7.0) | |
Abnormal | 33 (8.3) | 5 (1.2) | |
CA724f | 0.960 | ||
Normal | 563 (77.4) | 57 (7.8) | |
Abnormal | 97 (13.3) | 10 (1.5) | |
KRASg | 0.433 | ||
Wild type | 186 (51.2) | 27 (7.4) | |
Mutant type | 135 (37.2) | 15 (4.2) | |
NRASh | 0.604 | ||
Wild type | 315 (86.3) | 42 (11.5) | |
Mutant type | 8 (2.2) | 0 (0) | |
BRAFi | 1.000 | ||
Wild type | 235 (86.1) | 27 (9.9) | |
Mutant type | 10 (3.7) | 1 (0.3) | |
MMRj | 0.510 | ||
pMMR | 381 (65.8) | 39 (6.7) | |
dMMR | 147 (25.4) | 12 (2.1) |
表2 高风险与低风险患者临床病理因素相关分析[ n (%)]
Tab 2 Correlation analysis of clinicopathological factors between high-risk and low-risk patients [n(%)]
Indicator | Group | P value | |
---|---|---|---|
Low-risk | High-risk | ||
Gradea | 0.038* | ||
Well | 80 (8.4) | 2 (0.2) | |
Moderate | 667 (70.4) | 62 (6.5) | |
Poor | 120 (12.7) | 17 (1.8) | |
TNM Stagea | 0.000** | ||
Ⅰ | 157 (16.6) | 3 (0.3) | |
Ⅱ | 406 (42.8) | 15 (1.6) | |
Ⅲ | 298 (31.4) | 61 (6.4) | |
Ⅳ | 6 (0.7) | 2 (0.2) | |
T Stagea | 0.014* | ||
T1 | 36 (3.8) | 2 (0.2) | |
T2 | 144 (15.2) | 4 (0.4) | |
T3 | 187 (19.7) | 15 (1.6) | |
T4 | 500 (52.7) | 60 (6.4) | |
N Stagea | 0.000** | ||
N0 | 564 (59.5) | 19 (2.0) | |
N1 | 187 (19.7) | 34 (3.6) | |
N2 | 116 (12.2) | 28 (3.0) | |
Tumor location | 0.729 | ||
Right | 283 (29.9) | 25 (2.6) | |
Left | 232 (24.5) | 25 (2.6) | |
Rectal | 352 (37.1) | 31 (3.3) | |
Gendera | 0.009* | ||
Male | 490 (51.7) | 58 (6.1) | |
Female | 377 (39.8) | 23 (2.4) | |
Tumor sizea | 0.888 | ||
<5 cm | 539 (56.9) | 51 (5.4) | |
≥5 cm | 328 (34.6) | 30 (3.1) | |
Agea | 66.0 (58.0‒74.0) | 65.0 (54.5‒75.5) | 0.538 |
CEAb | 0.051 | ||
Normal | 432 (58.5) | 35 (4.7) | |
Abnormal | 240 (32.5) | 32 (4.3) | |
CA199c | 0.001** | ||
Normal | 540 (71.9) | 42 (5.6) | |
Abnormal | 143 (19.0) | 26 (3.5) | |
CA50d | 0.765 | ||
Normal | 318 (83.2) | 30 (7.9) | |
Abnormal | 30 (7.9) | 4 (1.0) | |
CA125e | 0.398 | ||
Normal | 334 (83.5) | 28 (7.0) | |
Abnormal | 33 (8.3) | 5 (1.2) | |
CA724f | 0.960 | ||
Normal | 563 (77.4) | 57 (7.8) | |
Abnormal | 97 (13.3) | 10 (1.5) | |
KRASg | 0.433 | ||
Wild type | 186 (51.2) | 27 (7.4) | |
Mutant type | 135 (37.2) | 15 (4.2) | |
NRASh | 0.604 | ||
Wild type | 315 (86.3) | 42 (11.5) | |
Mutant type | 8 (2.2) | 0 (0) | |
BRAFi | 1.000 | ||
Wild type | 235 (86.1) | 27 (9.9) | |
Mutant type | 10 (3.7) | 1 (0.3) | |
MMRj | 0.510 | ||
pMMR | 381 (65.8) | 39 (6.7) | |
dMMR | 147 (25.4) | 12 (2.1) |
Indicator | Univariate analysis | Multivariate analysis | |||||
---|---|---|---|---|---|---|---|
HR | 95%CI | P value | HR | 95%CI | P value | ||
Grade | |||||||
Well | ‒ | 1 | ‒ | ||||
Moderate | 2.333 | 0.945‒5.759 | 0.660 | ||||
Poor | 3.824 | 1.451‒10.079 | 0.007 | ||||
T Stage | |||||||
T1 | ‒ | 1 | ‒ | ||||
T2 | 1.897 | 0.240‒14.981 | 0.544 | ||||
T3 | 2.201 | 0.291‒16.676 | 0.445 | ||||
T4 | 6.070 | 0.845‒43.588 | 0.073 | ||||
N Stage | |||||||
N0 | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
N1 | 2.364 | 1.477‒3.784 | 0.000** | 1.971 | 1.211‒3.209 | 0.006* | |
N2 | 5.832 | 3.725‒9.130 | 0.000** | 5.648 | 3.510‒9.087 | 0.000** | |
Tumor location | |||||||
Right | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Left | 0.461 | 0.281‒0.757 | 0.002* | 0.483 | 0.291‒0.803 | 0.005* | |
Rectal | 0.472 | 0.307‒0.725 | 0.001* | 0.574 | 0.363‒0.906 | 0.017* | |
Gender | |||||||
Male | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Female | 0.602 | 0.402‒0.902 | 0.014* | 0.617 | 0.406‒0.937 | 0.023* | |
Tumor size | |||||||
<5 cm | ‒ | 1 | ‒ | ||||
≥5 cm | 1.294 | 0.887‒1.888 | 0.182 | ||||
Age | |||||||
≤67 years | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
>67 years | 3.315 | 2.188‒5.022 | 0.000** | 3.354 | 2.183‒5.152 | 0.000** | |
Risk group | |||||||
Low | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
High | 2.876 | 1.769‒4.676 | 0.000** | 2.078 | 1.236‒3.496 | 0.006* | |
CEA | |||||||
Normal | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Abnormal | 2.463 | 1.561‒3.887 | 0.000** | 1.729 | 1.045‒2.859 | 0.033* | |
CA199 | |||||||
Normal | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Abnormal | 1.719 | 1.053‒2.806 | 0.030* | 0.701 | 0.385‒1.275 | 0.244 | |
CA50 | |||||||
Normal | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Abnormal | 2.478 | 1.095‒5.607 | 0.029* | 1.975 | 0.772‒5.050 | 0.155 | |
CA125 | |||||||
Normal | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Abnormal | 2.690 | 1.293‒5.598 | 0.008* | 1.752 | 0.815‒3.766 | 0.151 | |
CA724 | |||||||
Normal | ‒ | 1 | ‒ | ||||
Abnormal | 1.044 | 0.548‒1.989 | 0.897 | ||||
KRAS | |||||||
Wild type | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Mutant type | 2.818 | 1.559‒5.092 | 0.001* | 2.048 | 1.108‒3.786 | 0.022* | |
NRAS | |||||||
Wild type | ‒ | 1 | ‒ | ||||
Mutant type | 2.009 | 0.487‒8.283 | 0.334 | ||||
BRAF | |||||||
Wild type | ‒ | 1 | ‒ | ||||
Mutant type | 2.242 | 0.534‒9.412 | 0.270 | ||||
MMR | |||||||
pMMR | ‒ | 1 | ‒ | ||||
dMMR | 1.343 | 0.767‒2.351 | 0.301 |
表3 CRC总体生存率影响因素的单因素和多因素COX 分析(SGH未匹配队列)
Tab 3 Univariate and multivariate COX analysis of influencing factors for overall survival of CRC (Unmatched queue of SGH)
Indicator | Univariate analysis | Multivariate analysis | |||||
---|---|---|---|---|---|---|---|
HR | 95%CI | P value | HR | 95%CI | P value | ||
Grade | |||||||
Well | ‒ | 1 | ‒ | ||||
Moderate | 2.333 | 0.945‒5.759 | 0.660 | ||||
Poor | 3.824 | 1.451‒10.079 | 0.007 | ||||
T Stage | |||||||
T1 | ‒ | 1 | ‒ | ||||
T2 | 1.897 | 0.240‒14.981 | 0.544 | ||||
T3 | 2.201 | 0.291‒16.676 | 0.445 | ||||
T4 | 6.070 | 0.845‒43.588 | 0.073 | ||||
N Stage | |||||||
N0 | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
N1 | 2.364 | 1.477‒3.784 | 0.000** | 1.971 | 1.211‒3.209 | 0.006* | |
N2 | 5.832 | 3.725‒9.130 | 0.000** | 5.648 | 3.510‒9.087 | 0.000** | |
Tumor location | |||||||
Right | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Left | 0.461 | 0.281‒0.757 | 0.002* | 0.483 | 0.291‒0.803 | 0.005* | |
Rectal | 0.472 | 0.307‒0.725 | 0.001* | 0.574 | 0.363‒0.906 | 0.017* | |
Gender | |||||||
Male | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Female | 0.602 | 0.402‒0.902 | 0.014* | 0.617 | 0.406‒0.937 | 0.023* | |
Tumor size | |||||||
<5 cm | ‒ | 1 | ‒ | ||||
≥5 cm | 1.294 | 0.887‒1.888 | 0.182 | ||||
Age | |||||||
≤67 years | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
>67 years | 3.315 | 2.188‒5.022 | 0.000** | 3.354 | 2.183‒5.152 | 0.000** | |
Risk group | |||||||
Low | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
High | 2.876 | 1.769‒4.676 | 0.000** | 2.078 | 1.236‒3.496 | 0.006* | |
CEA | |||||||
Normal | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Abnormal | 2.463 | 1.561‒3.887 | 0.000** | 1.729 | 1.045‒2.859 | 0.033* | |
CA199 | |||||||
Normal | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Abnormal | 1.719 | 1.053‒2.806 | 0.030* | 0.701 | 0.385‒1.275 | 0.244 | |
CA50 | |||||||
Normal | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Abnormal | 2.478 | 1.095‒5.607 | 0.029* | 1.975 | 0.772‒5.050 | 0.155 | |
CA125 | |||||||
Normal | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Abnormal | 2.690 | 1.293‒5.598 | 0.008* | 1.752 | 0.815‒3.766 | 0.151 | |
CA724 | |||||||
Normal | ‒ | 1 | ‒ | ||||
Abnormal | 1.044 | 0.548‒1.989 | 0.897 | ||||
KRAS | |||||||
Wild type | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Mutant type | 2.818 | 1.559‒5.092 | 0.001* | 2.048 | 1.108‒3.786 | 0.022* | |
NRAS | |||||||
Wild type | ‒ | 1 | ‒ | ||||
Mutant type | 2.009 | 0.487‒8.283 | 0.334 | ||||
BRAF | |||||||
Wild type | ‒ | 1 | ‒ | ||||
Mutant type | 2.242 | 0.534‒9.412 | 0.270 | ||||
MMR | |||||||
pMMR | ‒ | 1 | ‒ | ||||
dMMR | 1.343 | 0.767‒2.351 | 0.301 |
Indicator | Univariate analysis | Multivariate analysis | |||||
---|---|---|---|---|---|---|---|
HR | 95%CI | P value | HR | 95%CI | P value | ||
Grade | |||||||
Well | ‒ | 1 | ‒ | ||||
Moderate | 7 939.246 | 0‒3.338×1081 | 0.922 | ||||
Poor | 14 304.201 | 0‒6.019×1081 | 0.916 | ||||
T Stage | |||||||
T1 | ‒ | ‒ | ‒ | ||||
T2 | ‒ | 1 | ‒ | ||||
T3 | 23 440.882 | 0‒2.765×10167 | 0.958 | ||||
T4 | 75 016.020 | 0‒8.807×10167 | 0.953 | ||||
N Stage | |||||||
N0 | ‒ | 1 | ‒ | ||||
N1 | 1.474 | 0.453‒4.793 | 0.519 | ||||
N2 | 2.607 | 0.870‒8.192 | 0.086 | ||||
Tumor location | |||||||
Right | ‒ | 1 | ‒ | ||||
Left | 0.500 | 0.204‒1.227 | 0.130 | ||||
Rectal | 0.204 | 0.068‒0.615 | 0.005* | ||||
Gender | |||||||
Male | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Female | 0.602 | 0.402‒0.902 | 0.014* | 0.428 | 0.147‒1.246 | 0.120 | |
Tumor size | |||||||
<5 cm | ‒ | 1 | ‒ | ||||
≥5 cm | 1.846 | 0.855‒3.987 | 0.118 | ||||
Age | |||||||
≤67 years | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
>67 years | 3.092 | 1.377‒6.944 | 0.006* | 2.890 | 1.286‒6.494 | 0.010* | |
Risk group | |||||||
Low | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
High | 2.483 | 1.078‒5.720 | 0.033* | 2.380 | 1.030‒5.502 | 0.042* |
表4 CRC总体生存率影响因素的单因素和多因素COX 分析(SGH匹配队列)
Tab 4 Univariate and multivariate COX analysis of influencing factors for overall survival of CRC (matched queue of SGH)
Indicator | Univariate analysis | Multivariate analysis | |||||
---|---|---|---|---|---|---|---|
HR | 95%CI | P value | HR | 95%CI | P value | ||
Grade | |||||||
Well | ‒ | 1 | ‒ | ||||
Moderate | 7 939.246 | 0‒3.338×1081 | 0.922 | ||||
Poor | 14 304.201 | 0‒6.019×1081 | 0.916 | ||||
T Stage | |||||||
T1 | ‒ | ‒ | ‒ | ||||
T2 | ‒ | 1 | ‒ | ||||
T3 | 23 440.882 | 0‒2.765×10167 | 0.958 | ||||
T4 | 75 016.020 | 0‒8.807×10167 | 0.953 | ||||
N Stage | |||||||
N0 | ‒ | 1 | ‒ | ||||
N1 | 1.474 | 0.453‒4.793 | 0.519 | ||||
N2 | 2.607 | 0.870‒8.192 | 0.086 | ||||
Tumor location | |||||||
Right | ‒ | 1 | ‒ | ||||
Left | 0.500 | 0.204‒1.227 | 0.130 | ||||
Rectal | 0.204 | 0.068‒0.615 | 0.005* | ||||
Gender | |||||||
Male | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Female | 0.602 | 0.402‒0.902 | 0.014* | 0.428 | 0.147‒1.246 | 0.120 | |
Tumor size | |||||||
<5 cm | ‒ | 1 | ‒ | ||||
≥5 cm | 1.846 | 0.855‒3.987 | 0.118 | ||||
Age | |||||||
≤67 years | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
>67 years | 3.092 | 1.377‒6.944 | 0.006* | 2.890 | 1.286‒6.494 | 0.010* | |
Risk group | |||||||
Low | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
High | 2.483 | 1.078‒5.720 | 0.033* | 2.380 | 1.030‒5.502 | 0.042* |
Indicator | Univariate analysis | Multivariate analysis | |||||
---|---|---|---|---|---|---|---|
HR | 95%CI | P value | HR | 95%CI | P value | ||
Grade | |||||||
Well | ‒ | 1 | ‒ | ||||
Moderate | 0.975 | 0.424‒2.239 | 0.952 | ||||
Poor | 2.183 | 0.813‒5.866 | 0.122 | ||||
T Stage | |||||||
T1 | ‒ | 1 | ‒ | ||||
T2 | 12 594.988 | 0‒2.436×1059 | 0.884 | ||||
T3 | 8 970.864 | 0‒1.730×1059 | 0.889 | ||||
T4 | 7 939.965 | 0‒1.532×1059 | 0.890 | ||||
N Stage | |||||||
N0 | ‒ | 1 | ‒ | ||||
N1 | 2.137 | 1.078‒4.237 | 0.030* | ||||
N2 | 1.379 | 0.626‒3.038 | 0.426 | ||||
Tumor location | |||||||
Right | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Left | 0.409 | 0.183‒0.916 | 0.030* | 0.475 | 0.208‒1.085 | 0.077 | |
Rectal | 0.440 | 0.219‒0.886 | 0.021* | 0.450 | 0.223‒0.906 | 0.025* | |
Gender | |||||||
Male | ‒ | 1 | ‒ | ||||
Female | 0.708 | 0.386‒1.299 | 0.265 | ||||
Tumor size | |||||||
<5 cm | ‒ | 1 | ‒ | ||||
≥5 cm | 0.990 | 0.542‒1.808 | 0.975 | ||||
Age | |||||||
≤67 years | ‒ | 1 | ‒ | ||||
>67 years | 1.729 | 0.950‒3.147 | 0.073 | ||||
Risk group | |||||||
Low | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
High | 2.403 | 1.183‒4.882 | 0.015* | 2.121 | 1.024‒4.392 | 0.043* |
表5 CRC总体生存率影响因素的单因素和多因素COX分析(TMA队列)
Tab 5 Univariate and multivariate COX analysis of influencing factors for overall survival of CRC (TMA cohort)
Indicator | Univariate analysis | Multivariate analysis | |||||
---|---|---|---|---|---|---|---|
HR | 95%CI | P value | HR | 95%CI | P value | ||
Grade | |||||||
Well | ‒ | 1 | ‒ | ||||
Moderate | 0.975 | 0.424‒2.239 | 0.952 | ||||
Poor | 2.183 | 0.813‒5.866 | 0.122 | ||||
T Stage | |||||||
T1 | ‒ | 1 | ‒ | ||||
T2 | 12 594.988 | 0‒2.436×1059 | 0.884 | ||||
T3 | 8 970.864 | 0‒1.730×1059 | 0.889 | ||||
T4 | 7 939.965 | 0‒1.532×1059 | 0.890 | ||||
N Stage | |||||||
N0 | ‒ | 1 | ‒ | ||||
N1 | 2.137 | 1.078‒4.237 | 0.030* | ||||
N2 | 1.379 | 0.626‒3.038 | 0.426 | ||||
Tumor location | |||||||
Right | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
Left | 0.409 | 0.183‒0.916 | 0.030* | 0.475 | 0.208‒1.085 | 0.077 | |
Rectal | 0.440 | 0.219‒0.886 | 0.021* | 0.450 | 0.223‒0.906 | 0.025* | |
Gender | |||||||
Male | ‒ | 1 | ‒ | ||||
Female | 0.708 | 0.386‒1.299 | 0.265 | ||||
Tumor size | |||||||
<5 cm | ‒ | 1 | ‒ | ||||
≥5 cm | 0.990 | 0.542‒1.808 | 0.975 | ||||
Age | |||||||
≤67 years | ‒ | 1 | ‒ | ||||
>67 years | 1.729 | 0.950‒3.147 | 0.073 | ||||
Risk group | |||||||
Low | ‒ | 1 | ‒ | ‒ | 1 | ‒ | |
High | 2.403 | 1.183‒4.882 | 0.015* | 2.121 | 1.024‒4.392 | 0.043* |
图2 高风险组与低风险组的Kaplan-Meier生存分析曲线Note:A. SGH cohort (no matching). B. SGH cohort (matching). C. TMA cohort.
Fig 2 Kaplan-Meier survival analysis for overall survival of high-risk group and low-risk group
图3 高风险组与低风险组在肿瘤部位中的Kaplan-Meier生存分析曲线Note:A. Right-side colon cancer. B. Left-side colon cancer. C. Rectal cancer.
Fig 3 Kaplan-Meier survival analysis curves in tumor site between high risk group and low risk group
图4 高风险组与低风险组在TNM分期中的Kaplan-Meier生存分析曲线Note:A. Ⅱ stage. B. Ⅲ stage.
Fig 4 Kaplan-Meier survival analysis curves in TNM stage between high risk group and low risk group
图5 高风险组与低风险组在术前血清肿瘤标志物、基因突变状态、错配修复基因状态分布差异Note:A. CEA. B. CA199. C. CA50. D. CA125. E. CA724. F. KRAS. G. NRAS. H. BRAF. I. MMR.
Fig 5 Distributional difference of preoperative serum tumor markers, gene mutation status and mismatch repair gene status for high-risk group and low-risk group
图6 高风险组与低风险组Kaplan-Meier生存分析曲线Note:A. CEA in high risk group. B. CEA in low risk group. C. CEA in combined risk group. D. CA199 in high risk group. E. CA199 in low risk group. F. CA199 in combined risk group. G. KRAS in high risk group. H. KRAS in low risk group. I. KRAS in combined risk group.
Fig 6 Kaplan-Meier survival analysis curves for high risk group and low risk group
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