Acta Academiae Medicinae Sinica ›› 2018, Vol. 40 ›› Issue (6): 769-777.doi: 10.3881/j.issn.1000-503X.10493
• Original Articles • Previous Articles Next Articles
CUI Ge1,FENG Wenming2,ZHANG Ting3(),ZHU Guoliang1,SHI Qilin1,ZHANG Xiaolan1,XIA Hui1
Received:
2018-04-23
Online:
2018-12-20
Published:
2019-01-03
Supported by:
CLC Number:
CUI Ge,FENG Wenming,ZHANG Ting,ZHU Guoliang,SHI Qilin,ZHANG Xiaolan,XIA Hui. Validation and Evaluation of Diagnostic Efficiency of Genes Associated with Colorectal Cancer with Hyperglycemia[J].Acta Academiae Medicinae Sinica, 2018, 40(6): 769-777.
Table 1
Comparison of mRNA relative expressions of genes between tumor and normal tissues in colorectal cancer patients with different blood glucose levels (n=109,x?±s)"
分组Group | GRP78 | NOX1 | CEACAM5 | HSP60 | HDAC1 |
---|---|---|---|---|---|
HG-T | 1.818±0.507 | 1.995±0.486 | 2.145±0.320 | 1.888±0.280 | 1.768±0.390 |
NG-T | 1.108±0.250 | 1.248±0.278 | 1.064±0.190 | 1.011±0.155 | 1.229±0.230 |
HG-N | 1.510±0.234 | 1.481±0.333 | 1.852±0.422 | 1.528±0.426 | 2.130±0.338 |
NG-N | 1.000±0.000 | 1.000±0.000 | 1.000±0.000 | 1.000±0.000 | 1.000±0.000 |
t1 | 0.917 | 3.495 | 0.616 | 0.142 | 2.486 |
P1 | 0.379 | 0.005 | 0.550 | 0.889 | 0.030 |
t2 | 3.437 | 4.192 | 7.837 | 5.135 | 4.614 |
P2 | 0.006 | 0.002 | 0.000 | 0.000 | 0.001 |
t3 | 1.206 | 1.771 | 1.151 | 1.255 | 2.793 |
P3 | 0.253 | 0.104 | 0.274 | 0.235 | 0.017 |
t4 | 5.086 | 11.360 | 11.767 | 17.227 | 13.960 |
P4 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |
Table 2
Comparison of mRNA relative expressions of genes in serum of colorectal cancer patients with different blood glucose levels,diabetic patients,and healthy volunteers (x?±s)"
分组Group | GRP78 | NOX1 | CEACAM5 | HSP60 | HDAC1 |
---|---|---|---|---|---|
HG-T(n=34) | 1.018±0.240 | 1.322±0.240 | 1.064±0.330 | 3.501±0.009 | 2.527±0.009 |
NG-T(n=75) | 2.797±0.380 | 2.019±0.250 | 2.779±0.370 | 1.495±0.009 | 2.028±0.240 |
DM(n=30) | 1.704±0.770 | 1.269±0.690 | 1.378±0.650 | 1.233±0.007 | 1.148±0.210 |
N(n=30) | 1.000±0.000 | 1.000±0.000 | 1.000±0.000 | 1.000±0.007 | 1.000±0.000 |
t1 | 0.971 | 3.198 | 0.820 | 4.489 | 5.088 |
P1 | 0.310 | 0.008 | 0.430 | 0.001 | 0.000 |
t2 | 3.520 | 6.370 | 8.058 | 4.361 | 7.249 |
P2 | 0.005 | 0.000 | 0.000 | 0.001 | 0.000 |
t3 | 4.364 | 8.054 | 8.965 | 4.952 | 5.440 |
P3 | 0.001 | 0.000 | 0.000 | 0.000 | 0.000 |
t4 | 1.038 | 1.854 | 1.346 | 1.815 | 2.585 |
P4 | 0.322 | 0.091 | 0.205 | 0.097 | 0.025 |
t5 | 3.158 | 5.998 | 7.754 | 3.496 | 4.451 |
P5 | 0.009 | 0.000 | 0.000 | 0.005 | 0.001 |
Table 3
Correlation of the expressions of genes associated with colorectal cancer and clinicopathological parameters in colorectal cancer patients with different blood glucose levels"
基因 Gene | 性别 Gender | 年龄 Age | 空腹血糖 Fasting blood glucose | 肿瘤部位 Tumor site | 大体分型 General classification | 肿瘤直径 Tumor diameter | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
r | P | r | P | r | P | r | P | r | P | r | P | |
GRP78 | 0.093 | 0.664 | 0.218 | 0.306 | 0.490 | 0.001 | 0.106 | 0.623 | 0.106 | 0.623 | 0.184 | 0.390 |
NOX1 | 0.261 | 0.218 | 0.265 | 0.210 | 0.335 | 0.022 | 0.049 | 0.821 | 0.213 | 0.557 | 0.365 | 0.013 |
CEACAM5 | 0.360 | 0.084 | 0.010 | 0.963 | 0.514 | 0.000 | 0.103 | 0.632 | 0.184 | 0.577 | 0.207 | 0.332 |
HSP60 | 0.112 | 0.601 | 0.443 | 0.030 | 0.294 | 0.044 | 0.195 | 0.362 | 0.179 | 0.590 | 0.111 | 0.607 |
HDAC1 | 0.129 | 0.548 | 0.025 | 0.907 | 0.291 | 0.047 | 0.405 | 0.049 | 0.187 | 0.397 | 0.242 | 0.254 |
基因 Gene | 神经血管累及 Neurovascular involvement | 分化程度 Degree of differentiation | 原发灶浸润深度 Depth of primary infiltration | 淋巴结转移 Lymph node metastasis | 远处转移 Distant metastases | TNM分期 TNM staging | ||||||
r | P | r | P | r | P | r | P | r | P | r | P | |
GRP78 | 0.598 | 0.016 | 0.215 | 0.313 | 0.159 | 0.457 | 0.079 | 0.712 | 0.582 | 0.787 | 0.031 | 0.885 |
NOX1 | 0.249 | 0.240 | 0.017 | 0.937 | 0.128 | 0.534 | 0.145 | 0.500 | 0.124 | 0.565 | 0.136 | 0.527 |
CEACAM5 | 0.429 | 0.036 | 0.002 | 0.994 | 0.571 | 0.036 | 0.222 | 0.298 | 0.190 | 0.373 | 0.697 | 0.014 |
HSP60 | 0.156 | 0.468 | 0.179 | 0.404 | 0.164 | 0.488 | 0.118 | 0.583 | 0.186 | 0.384 | 0.274 | 0.195 |
HDAC1 | 0.242 | 0.255 | 0.026 | 0.905 | 0.559 | 0.025 | 0.215 | 0.313 | 0.159 | 0.458 | 0.508 | 0.042 |
Table 4
Area under ROC curves and cut-off values of the exressions of genes associated with colorectal cancer in colorectal cancer patients with hyperglycemia"
基因 Gene | ROC曲线 下面积 Area under ROC curve | 标准误 Standard error | P | 95%CI | 诊断临界点 Cut-off value |
---|---|---|---|---|---|
GRP78 | 0.777 | 0.072 | 0.004 | 0.635-0.918 | 0.011 |
NOX1 | 0.931 | 0.055 | 0.000 | 0.824-1.000 | 0.047 |
CEACAM5 | 0.852 | 0.054 | 0.000 | 0.746-0.958 | 0.021 |
HSP60 | 0.649 | 0.094 | 0.125 | 0.465-0.834 | 0.042 |
HDAC1 | 0.860 | 0.055 | 0.000 | 0.751-0.969 | 0.049 |
Table 5
Two by two table for diagnostic test of genes associated with colorectal cancer(n)"
基因 Gene | 真阳性 表达数 (a) True positive number(a) | 假阳性 表达数 (b) False positive number(b) | 假阴性 表达数 (c) False negative number(c) | 真阴性 表达数 (d) True negative number(d) |
---|---|---|---|---|
GRP78 | 32 | 36 | 45 | 56 |
NOX1 | 34 | 8 | 8 | 119 |
CEACAM5 | 29 | 24 | 14 | 102 |
HSP60 | 28 | 16 | 27 | 98 |
HDAC1 | 34 | 7 | 8 | 120 |
Table 6
Diagnostic test of genes associated with colorectal cancer in serum specimens of colorectal cancer patients with hyperglycemia"
基因 Gene | 灵敏度 Sensitivity (%) | 特异度 Specificity (%) | 准确度 Accuracy (%) | 正确指数 Youden index (%) | 阳性似然比 Positive likelihood ratio | 阴性似然比 Negative likelihood ratio | 阳性预测值 Positive predictive value(%) | 阴性预测值 Negative predictive value(%) |
---|---|---|---|---|---|---|---|---|
GRP78 | 41.56 | 60.87 | 52.07 | 2.43 | 1.06 | 0.96 | 47.06 | 55.45 |
NOX1 | 80.95 | 93.70 | 90.53 | 74.65 | 12.85 | 0.20 | 80.95 | 93.70 |
CEACAM5 | 67.44 | 80.95 | 77.51 | 48.39 | 3.54 | 0.40 | 54.72 | 87.93 |
HSP60 | 50.91 | 85.96 | 74.56 | 36.87 | 3.63 | 0.57 | 63.64 | 78.40 |
HDAC1 | 80.95 | 94.49 | 91.12 | 75.44 | 14.69 | 0.20 | 82.93 | 93.75 |
Table 7
Diagnostic test of combined detection of genes associated with colorectal cancer in serum specimens of colorectal cancer patients with hyperglycemia(%)"
基因联合检测 Combined genes detection | 平行试验Parallel test | 序列试验Serial test | ||
---|---|---|---|---|
灵敏度 Sensitivity | 特异度 Specificity | 灵敏度 Sensitivity | 特异度 Specificity | |
NOX1+CEACAM5 | 93.80 | 75.85 | 54.59 | 98.80 |
NOX1+HDAC1 | 96.37 | 88.54 | 65.53 | 99.65 |
CEACAM5+HDAC1 | 93.80 | 76.49 | 54.59 | 98.95 |
NOX1+CEACAM5+HDAC1 | 98.82 | 71.67 | 44.19 | 99.93 |
[1] |
Jullumstrø E, Kollind M, Lydersen S , et al. Diabetes mellitus and outcomes of colorectal cancer[J]. Acta Oncologica, 2009,48(3):361. DOI: 10.1080/02841860802637765.
doi: 10.1080/02841860802637765 pmid: 19101848 |
[2] |
González N, Prieto I,del Puerto-Nevado L ,et al. 2017 update on the relationship between diabetes and colorectal cancer:epidemiology,potential molecular mechanisms and therapeutic implications[J]. Oncotarget, 2017,8(11):18456-18485. DOI: 10.18632/oncotarget.14472.
doi: 10.18632/oncotarget.14472 pmid: 28060743 |
[3] |
Mills KT, Bellows CF, Hoffman AE , et al. Diabetes mellitus and colorectal cancer prognosis:a meta-analysis[J]. Dis Colon Rectum, 2013,56(11):1304-1319. DOI: 10.1097/DCR.0b013e3182a479f9.
doi: 10.1097/DCR.0b013e3182a479f9 |
[4] |
Vulcan A, Manjer J, Ohlsson B . High blood glucose levels are associated with higher risk of colon cancer in men:a cohort study[J]. BMC Cancer, 2017,17(1):842. DOI: 10.1186/s12885-017-3874-4.
doi: 10.1186/s12885-017-3874-4 pmid: 5727949 |
[5] |
Jiang Y, Ben Q, Shen H , et al. Diabetes mellitus and incidence and mortality of colorectal cancer:a systematic review and meta-analysis of cohort studies[J]. Eur J Epidemiol, 2011,26(11):863-876. DOI: 10.1007/s10654-011-9617-y.
doi: 10.1007/s10654-011-9617-y pmid: 21938478 |
[6] |
Cui G, Zhang T, Ren F , et al. High blood glucose levels correlate with tumor malignancy in colorectal cancer patients[J]. Med Sci Monit, 2015,21(12):3825-3833. DOI: 10.12659/MSM.894783.
doi: 10.12659/MSM.894783 pmid: 26644185 |
[7] |
Casas C . GRP78 at the centre of the stage in cancer and neuroprotection[J]. Front Neurosci-Switz, 2017,11(4):177. DOI: 10.3389/fnins.2017.00177.
doi: 10.3389/fnins.2017.00177 pmid: 28424579 |
[8] |
牛哲禹, 刘乔飞, 王梦一 , 等. 葡萄糖调节蛋白78在小鼠胰腺癌发生演进过程中的表达变化[J]. 中国医学科学院学报, 2015,37(3):259-263. DOI: 10.3881/j.issn.1000-503X.2015.03.002.
doi: 10.3881/j.issn.1000-503X.2015.03.002 |
[9] |
Prasad M, Pawlak KJ, Burak WE , et al. Mitochondrial metabolic regulation by GRP78[J]. Sci Adv, 2017,3(2):e1602038. DOI: 10.1126/sciadv.1602038.
doi: 10.1126/sciadv.1602038 |
[10] |
刘洋, 谢蓉, 王秀敏 , 等. GRP78异常O-糖基化对乳腺癌细胞侵袭迁移的影响[J]. 河北大学学报(自然科学版), 2018,38(1):65-72. DOI: 10.3969/j.issn.1000-1565.2018.01.011.
doi: 10.3969/j.issn.1000-1565.2018.01.011 |
[11] |
Gray SP, Marco ED, Okabe J , et al. Nox1 plays a key role in diabetes accelerated atherosclerosis[J]. Circulation, 2013,127(18):1888-1902. DOI: 10.1161/CIRCULATIONAHA.112.132159.
doi: 10.1161/CIRCULATIONAHA.112.132159 |
[12] |
Pekarcíková L, Knopfová L, Benes P , et al. c-Myb regulates NOX1/p38 to control survival of colorectal carcinoma cells[J]. Cell Signal, 2016,28(8):924-936. DOI: 10.1016/j.cellsig.2016.04.007.
doi: 10.1016/j.cellsig.2016.04.007 pmid: 27107996 |
[13] |
Panettieri E, Ardito F, Giuliante F , et al. CEACAM5 mRNA in blood as prognostic biomarker of early recurrence in liver metastatic colorectal cancer patients[J]. Ejso-Eur J Surg Onc, 2018,44(4):554-555. DOI: 10.1016/j.ejso.2018.01.073.
doi: 10.1016/j.ejso.2018.01.073 |
[14] |
Zayed AA, Beano AM, Amer FN , et al. Serum levels of carcinoembryonic antigen (cea) in patients with type 2 diabetes[J]. Endocr Pract, 2016,22(11):1310. DOI: 10.4158/EP161221.OR.
doi: 10.4158/EP161221.OR pmid: 27482614 |
[15] |
Joshua J, Martinus RD . Does Hsp60 provide a link between mitochondrial stress and inflammation in diabetes mellitus?[J]. J Diabetes Res, 2016,2016(3):8017571. DOI: 10.1155/2016/8017571.
doi: 10.1155/2016/8017571 pmid: 4960334 |
[16] |
Tong WW, Tong GH, Liu Y . The tumor promoting roles of HSP60 and HIF2α in gastric cancer cells[J]. Tumour Biol, 2016,37(7):1-6. DOI: 10.1007/s13277-015-4783-2.
doi: 10.1007/s13277-015-4783-2 pmid: 26810190 |
[17] |
Balliu M, Cellai C, Lulli M , et al. HDAC1 controls CIP2A transcription in human colorectal cancer cells[J]. Oncotarget, 2016,7(18):25862-25871. DOI: 10.1007/s13277-015-4783-2.
doi: 10.1007/s13277-015-4783-2 pmid: 5041950 |
[18] |
Citro S, Miccolo C, Meloni L , et al. PI3K/mTOR mediate mitogen-dependent HDAC1 phosphorylation in breast cancer:a novel regulation of estrogen receptor expression[J]. J Mol Cell Biol, 2015,7(2):132-142. DOI: 10.1093/jmcb/mjv021.
doi: 10.1093/jmcb/mjv021 pmid: 25801958 |
[19] |
董梅, 胡兴胜, 陈闪闪 , 等. 组蛋白去乙酰化酶抑制剂在肿瘤治疗领域的进展[J]. 中华肿瘤杂志, 2013,35(7):481-485. DOI: 10.3760/cma.j.issn.0253-3766.2013.07.001.
doi: 10.3760/cma.j.issn.0253-3766.2013.07.001 |
[20] |
Alberti KG, Zimmet PZ . Definition,diagnosis and classification of diabetes mellitus and its complications. Part 1:diagnosis and classification of diabetes mellitus provisional report of a WHO consultation[J]. Diabet Med, 1998,15(7):539-553. DOI: 10.1002/(SICI)1096-9136(199807)15:7<539:AID-DIA668>3.0.CO;2-S.
doi: 10.1002/(SICI)1096-9136(199807)15:7<539:AID-DIA668>3.0.CO pmid: 96866939686693 |
[21] |
American Diabetes Association . Diagnosis and classification of diabetes mellitus[J]. Diabetes Care, 2004,27(Suppl 1):S5-S10. DOI: 10.2337/diacare.27.2007.S5.
doi: 10.2337/diacare.27.2007.S5 |
[22] |
李增山, 李青 . 2010年版消化系统肿瘤WHO分类解读[J]. 中华病理学杂志, 2011,40(5):351-354. DOI: 10.3760/cma.j.issn.0529-5807.2011.05.019.
doi: 10.3760/cma.j.issn.0529-5807.2011.05.019 |
[23] |
Wittekind C . 2010 TNM system:on the 7th edition of TNM classification of malignant tumors[J]. Der Pathologe, 2010,31(5):331-332. DOI: 10.1007/s00292-010-1349-3.
doi: 10.1007/s00292-010-1349-3 pmid: 20703480 |
[24] |
卫生部医政司, 结直肠癌诊疗规范专家工作组. 结直肠癌诊疗规范(2010年版)[J]. 中华胃肠外科杂志, 2010,13(11):865-875. DOI: 10.3760/cma.j.issn.1671-0274.2010.11.028.
doi: 10.3760/cma.j.issn.1671-0274.2010.11.028 |
[25] |
中华医学会消化内镜学分会, 中国抗癌协会肿瘤内镜学专业委员会. 中国早期结直肠癌筛查及内镜诊治指南(2014,北京)[J]. 中华医学杂志, 2015,95(28):2235-2252. DOI: 10.3760/cma.j.issn.0376-2491.2015.28.002.
doi: 10.3760/cma.j.issn.0376-2491.2015.28.002 |
[1] | LIU Ying-jiu, WEN Yu-bing, TAO Jian-ling, LI Jin-hong, SU Ying, YE Wei, LI Hang, LI Xue-mei, LI Xue-wang. Correlations of Podocyte Injury with Glucose Regulated Protein 78 Expression and Proteinuria in Patients with Diabetic Nephropathy [J]. Acta Academiae Medicinae Sinica, 2012, 34(4): 359-363. |
Viewed | ||||||
Full text |
|
|||||
Abstract |
|
|||||
|