MMP-9和TIMP-1表达在胃癌根治术后患者预后评估中的作用

doi:10.13481/j.1671-587X.20220120

Abstract

Abstract: Objective

To analyze the expressions of matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of metalloproteinase-1 （TIMP-1） in cancer tissue of the gastric cancer patients， and to investigate their values in prognostic evaluation of the gastric cancer patients underwent radical gastrectomy.

Methods

A total of 270 gastric cancer patients who underwent radical gastrectomy were enrolled in this study， and the positive expression rates of MMP-9 and TIMP-1 in cancer tissue of the patients were detected by immunohistochemistry method. Pearson χ² or Fisher’s exact test was used to assess the distribution of MMP-9 and TIMP-1 positive expressions in the gastric cancer patients with different clinicopathological parameters. Survival curves were plotted using Kaplan-Meier method and the differences were assessed by Log-rank test. Multivariate Cox regression model was conducted to analyze the relationships between the expressions of MMP-9 and TIMP-1 and the prognosis of the gastric cancer patients underwent radical gastrectomy.

Results

Among the 270 gastric cancer patients， MMP-9 and TIMP-1 were expressed in cytoplasm or cell membrane of tumor cells， and the positive expression rates of MMP-9 and TIMP-1 were 30.4% and 26.3%， respectively. No correlations between the co-expression of MMP-9， TIMP-1 and the age，gender，tumor size，tumor type，histological type，chemotherapy after operation，and TNM stage of the patients were identified. The results of Cox regression model showed that co-expression of MMP-9 and TIMP-1， postoperative chemotherapy and TNM stage were the significant independent factors for the prognosis of the gastric cancer patients. The gastric cancer patients with MMP-9 positive expression showed the better survival， and among the patients withMMP-9 negative expression， the risk of death in the patients with TIMP-1 positive expression was increased， which indicated the worse prognosis（MMP-9⁺/TIMP-1^+/－vs MMP-9^－/TIMP-1⁺：HR=0.537， 95% CI： 0.338－0.851，P=0.008）. Furthermore， compared with the patients with postoperative chemotherapy and TNM stage Ⅰ/Ⅱ， the patients with no-postoperative chemotherapy and TNM stage Ⅲ had higher risk of death and worse prognosis（HR=1.873，95% CI： 1.334－2.631，P<0.001； HR=2.301， 95% CI： 1.656－3.197， P<0.001）.In the subgroup analysis， among the gastric cancer patients with TNM stage Ⅰ/Ⅱ， postoperative chemotherapy or no signet-ring cell cancers， the risk of death in MMP-9⁺ group was decreased compared with MMP-9^－/TIMP-1⁺ subgroup （P<0.05），which indicated the better prognosis.

Conclusion

Co-expression of MMP-9 and TIMP-1 could serve as an independent prognostic predictor in the gastric cancer patients underwent radical gastrectomy； No postoperative chemotherapy and TNM stage Ⅲ are the risk factors for the prognosis of gastric cancer patients underwent radical gastrectomy.

Key words: Matrix metalloproteinase-9, Tissue inhibitor of metalloproteinase-1, Stomach neoplasms, Prognosis, Radical gastrectomy

CLC Number:

R735.2

Lili QIN,Xiaobo MA,Tianye ZHAO,Xuerong TAO,Min ZHENG,Xueying WANG,Jiaxin YI,Yanhua WU,Jing JIANG. Effects of MMP-9 and TIMP-1 expressions on prognostic evaluation of gastric cancer patients after radical gastrectomy[J].Journal of Jilin University(Medicine Edition), 2022, 48(1): 163-171.

Figures/Tables 6

Tab.2

Fig. 1

Tab.3

Tab.4

Fig.2

References 30

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Tab. 1 Baseline characteristics ofgastric cancer patients
Characteristic	Number (n)	Proportion (η/%)
Age(year)
≤65	162	60.0
>65	108	40.0
Gender
Female	65	24.1
Male	205	75.9
Tumor size
<5 cm	82	30.4
≥5 cm	188	69.6
Type
Signet ring cell	30	11.1
Others	240	88.9
Histological grade
Low grade	57	21.1
High grade	213	78.9
Chemotherapy
Yes	118	43.7
No	152	56.3
TNM stage
Ⅰ/Ⅱ stage	165	61.1
Ⅲ stage	105	38.9
Event
Live	99	36.7
Lose	11	4.1
Death	160	59.2
MMP-9
－	188	69.6
+	82	30.4
TIMP-1
－	199	73.7
+	71	26.3
MMP-9/TIMP-1
－/+	47	17.4
－/－	141	52.2
+/－	58	21.5
+/+	24	8.9

Clinicopathological parameters	MMP-9^－/TIMP-1^－ (n=141)	MMP-9⁺/TIMP-1^－(n=58)	MMP-9^－/TIMP-1⁺ （n=47）	MMP-9⁺/TIMP-1⁺ (n=24)	P
Age(year)
≤65	86(61.0)	29(50.0)	31(66.0)	16(66.7)	0.306
>65	55(39.0)	29(50.0)	16(34.0)	8(33.3)
Gender
Female	28(19.9)	14(24.1)	17(36.2)	6(25.0)	0.161
Male	113(80.1)	44(75.9)	30(63.8)	18(75.0)
Tumor size
<5 cm	45(31.9)	13(22.4)	19(40.4)	5(20.8)	0.159
≥5 cm	96(68.1)	45(77.6)	28(59.6)	19(79.2)
Type
Others	127(90.1)	51(87.9)	42(89.4)	20(83.3)	0.740^*
Signet ring cell	14(9.9)	7(12.1)	5(10.6)	4(16.7)
Grade
Low	30(21.3)	9(15.5)	12(25.5)	6(25.0)	0.602
High	111(78.7)	49(84.5)	35(74.5)	18(75.0)
Chemotherapy
Yes	63(44.7)	18(31.0)	23(48.9)	14(58.3)	0.092
No	78(55.3)	40(69.0)	24(51.1)	10(41.7)
TNM stage
Ⅰ/Ⅱ	85(60.3)	37(63.8)	27(57.4)	16(66.7)	0.851
Ⅲ	56(39.7)	21(36.2)	20(42.6)	8(33.3)

Clinicopathological parameter	n	Number of event [n（η/%）］	MST^*(month)	Ρ
Age(year)
≤65	162	90(55.6)	36.0	0.241
>65	108	70(64.8)	27.0
Gender
Female	65	40(61.5)	26.0	0.549
Male	205	120(58.5)	33.0
Tumor size
<5 cm	82	44(53.7)	42.0	0.114
≥5 cm	188	116(61.7)	26.0
Grade
Low	57	26(45.6)	72.0	0.007
High	213	134(62.9)	26.0
Type
Others	30	20(66.7)	28.0	0.318
Signet ring	240	140(58.3)	31.0
Chemotherapy
Yes	118	57(48.3)	47.0	<0.001
No	152	103(67.8)	21.0
TNM stage
Ⅰ/Ⅱ	165	77(46.7)	72.0	<0.001
Ⅲ	105	83(79.0)	15.0

Clinicopathological parameter	B	SE	Wald	HR	95%CI	Ρ
Age	0.063	0.169	0.137	1.065	0.764－1.483	0.711
Gender	0.013	0.187	0.005	1.013	0.702－1.461	0.944
Tumor size	0.170	0.184	0.847	1.185	0.826－1.701	0.357
Tumor type	－0.071	0.245	0.083	0.932	0.576－1.507	0.773
Histological grade	0.413	0.229	3.247	1.511	0.964－2.366	0.072
Chemotherapy	0.628	0.173	13.118	1.873	1.334－2.631	<0.001
TNM stage	0.833	0.168	24.680	2.301	1.656－3.197	<0.001
MMP-9/TIMP-1
MMP-9^－/TIMP-1⁺	－	－	7.093	－	－	0.029
MMP-9^－/TIMP-1^－	－0.379	0.203	3.489	0.684	0.460－1.019	0.062
MMP-9⁺/TIMP-1^+/－	－0.623	0.235	7.003	0.537	0.338－0.851	0.008
“－”:No data.

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Effects of MMP-9 and TIMP-1 expressions on prognostic evaluation of gastric cancer patients after radical gastrectomy

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