高血糖状态结直肠癌相关基因的验证及其诊疗效能评估

doi:10.3881/j.issn.1000-503X.10493

Acta Academiae Medicinae Sinica

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

Validation and Evaluation of Diagnostic Efficiency of Genes Associated with Colorectal Cancer with Hyperglycemia

CUI Ge¹,FENG Wenming²,ZHANG Ting³(),ZHU Guoliang¹,SHI Qilin¹,ZHANG Xiaolan¹,XIA Hui¹

1Department of Pathology,Huzhou,Zhejiang 313000,China
2Department of Surgery,First Affiliated Hospital of Huzhou University,Huzhou,Zhejiang 313000,China
3Department of Pathology,Medical college,Huzhou University,Huzhou,Zhejiang 313000,China

Received:2018-04-23 Online:2018-12-20 Published:2019-01-03
Supported by:
Supported by the Natural Sciences Foundation of Zhejiang Province(LQ16C080001);Public Welfare Technical Applied Research Project of Zhejiang Province Laboratory Animal Research(2017C37177);Medical Scientific Research Project of Zhejiang Province(2018KY775);Science and Technology Project of Huzhou City(2015GZ14)

Abstract

Abstract:

Objective To verify the expressions of genes associated with colorectal cancer with hyperglycemia and evaluate their diagnostic values.
Methods Tumor tissues,distal normal intestinal mucosa,and peripheral blood samples were harvested from 109 colorectal cancer patients and peripheral blood samples from 30 diabetes patients and 30 healthy volunteers. The mRNA expressions of glucose regulated protein 78 (GRP78),NADPH oxidase-1 (NOX1),carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5),heat shock protein 60 (HSP60),and histone deacetylase 1(HDAC1) were detected by real-time quantitative polymerase chain reaction. The correlation between the gene expressions and clinicopathological parameters in colorectal cancer patients were analyzed using Pearson’s correlation analysis. Diagnostic test accuracy evaluation was used to calculate the sensitivity,specificity,accuracy,predictability,Youden index,and likelihood ratio of serum gene expressions in colorectal cancer patients,and the receiver operating characteristic (ROC) curves were drawn. The area under the ROC curve was calculated to evaluate the diagnostic efficiency of the combined detection of multiple genes.
Results The mRNA levels of GRP78 (P=0.001),NOX1 (P=0.022),CEACAM5 (P=0.000),HSP60 (P=0.044),and HDAC1 (P=0.047) were positively correlated with the fasting blood glucose level. The mRNA expressions of NOX1 (P=0.000,P=0.008) and HDAC1 (P=0.000,P=0.037) in tissues and serum were significantly higher in colorectal cancer patients than in patients with normal blood glucose levels. The NOX1 mRNA expression was positively correlated with the diameter of colorectal cancer (P=0.013),and the HDAC1 mRNA expression was significantly correlated with the tumor site (P=0.049),depth of primary tumor invasion (P=0.025),and TNM stage (P=0.042). The areas under the ROC curves of NOX1,CEACAM5,and HDAC1 were 0.931,0.852,and 0.860 respectively (all P=0.000). The specificity,accuracy,and negative predictive value of NOX1,HDAC1 mRNA expression in colorectal cancer patients with hyperglycemia were all above 90%. The diagnostic sensitivity and specificity of the combined detection of NOX1,CEACAM5,and HDAC1 were 98.82% and 99.93%,respectively.
Conclusion Combined detection of genes associated with colorectal cancer accompanied by hyperglycemia can improve the diagnostic efficiency of early screening.

Key words: colorectal cancer with hyperglycemia, relative gene, glucose regulated protein 78, NADPH oxidase-1, carcinoembryonic antigen-related cell adhesion molecule 5, heat shock protein 60, histone deacetylase 1

CLC Number:

R73-3

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.

Figures/Tables 8

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References 25

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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

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

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
基因 Gene	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
基因 Gene	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

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

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

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Validation and Evaluation of Diagnostic Efficiency of Genes Associated with Colorectal Cancer with Hyperglycemia

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References 25

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基因联合检测 Combined genes detection	平行试验Parallel test		序列试验Serial test
基因联合检测 Combined genes detection	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

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