神经周围浸润、淋巴脉管浸润联合肿瘤间质比对胃癌预后的预测价值

doi:10.3877/cma.j.issn.1674-0793.2023.03.006

中华普通外科学文献(电子版) ›› 2023, Vol. 17 ›› Issue (03) : 186 -192. doi: 10.3877/cma.j.issn.1674-0793.2023.03.006

论著

神经周围浸润、淋巴脉管浸润联合肿瘤间质比对胃癌预后的预测价值

程非池, 邱佳辉, 郑扬, 蔡谦谦, 张人超, 裘正军, 黄陈^†(

)

233000　蚌埠医学院研究生院；200080　上海交通大学医学院附属第一人民医院胃肠外科
200080　上海交通大学医学院附属第一人民医院胃肠外科

收稿日期:2023-02-07 出版日期:2023-06-01
通信作者: 黄陈
基金资助:
国家自然科学基金项目(82072662); 上海申康医院发展中心临床三年行动计划(SHDC2020CR4022); CSCO-青年创新肿瘤研究基金项目(Y-Young2020-0458)

Prognostic value of perineural invasion, lymphovascular invasion combined with tumor stroma ratio in gastric cancer

Feichi1 Cheng, Jiahui Qiu, Yang Zheng, Qianqian Cai, Renchao Zhang, Zhengjun Qiu, Chen Huang^†()

Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
Graduate School of Bengbu Medicial University, Bengbu 233000, China; Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China

Received:2023-02-07 Published:2023-06-01
Corresponding author: Chen Huang

全文 ( ) 下载PDF ( ) 导出引用

引用本文：

程非池, 邱佳辉, 郑扬, 蔡谦谦, 张人超, 裘正军, 黄陈. 神经周围浸润、淋巴脉管浸润联合肿瘤间质比对胃癌预后的预测价值[J]. 中华普通外科学文献(电子版), 2023, 17(03): 186-192.

Feichi1 Cheng, Jiahui Qiu, Yang Zheng, Qianqian Cai, Renchao Zhang, Zhengjun Qiu, Chen Huang. Prognostic value of perineural invasion, lymphovascular invasion combined with tumor stroma ratio in gastric cancer[J]. Chinese Archives of General Surgery(Electronic Edition), 2023, 17(03): 186-192.

目的

分析胃癌术后患者病理特征神经周围浸润（PNI）、淋巴脉管浸润（LVI）、肿瘤间质比（TSR）与预后的联系，为PNI阳性、LVI阳性、高TSR的"三阳胃癌"的预后判断和临床诊疗策略提供新依据。

方法

选取上海交通大学医学院附属第一人民医院2012年12月至2019年12月间行胃癌根治术的胃癌患者745例（SGH队列）以及2014年1月至2018年9月间蚌埠医学院附属第一医院共131例胃癌患者（BMH队列）。采用Kaplan-Meier曲线进行生存分析并进行Log-rank检验。Cox比例风险回归分析筛选影响胃癌预后的独立危险因素，并建立列线图模型。绘制受试者工作特征（ROC）曲线、校准曲线，计算曲线下面积（AUC）以评估模型的预测效能，采用验证集进行外部验证。

结果

多因素Cox分析显示，PNI、LVI、TSR是除pTNM分期外的独立预后病理因素，且三者的发生相互关联。三阳组（LVI阳性、PNI阳性、高TSR）与两阳组（LVI阳性、PNI阳性、高TSR中任意两项）在肿瘤性质、肿瘤大小、pTNM分期、原发部位和病理分级中总生存率（OS）均显示出差异，其中印戒细胞癌、大肿瘤（≥5 cm），Ⅲ期、非远近端胃、低分化且被归为三阳组的患者预后最差，5年OS分别为0、12.4%、12.6%、13.8%、14.9%。基于pTNM、三阳分类、癌胚抗原（CEA）和淋巴细胞-单核细胞比值（LMR）建立的列线图预测模型，预测术后OS的ROC AUC为0.744（95% CI：0.704~0.784），表现出良好的预测价值。

结论

LVI阳性、PNI阳性、高TSR的"三阳胃癌"预后不良，基于pTNM、三阳分类、CEA和LMR建立的列线图预测模型，可以作为肿瘤-淋巴结-转移病理分期系统对预后预测的补充，有助于胃癌患者术后病情发展的评估及治疗方案的制定。

关键词: 胃肿瘤, 预后, 神经周围浸润, 淋巴脉管浸润, 肿瘤间质比

Objective

To analyze the relationship among postoperative pathological characteristics such as perineural invasion (PNI), lymphovascular invasion (LVI), tumor stroma ratio (TSR) and the prognosis of patients with gastric cancer, providing a new basis for the prognosis, clinical diagnosis and treatment strategy of " Sanyang gastric cancer " characterized by PNI positive, LVI positive and high TSR.

Methods

A total of 745 patients with gastric cancer undergoing radical gastritis from December 2012 to December 2019 (SGH cohort) and 131 patients with gastric cancer from January 2014 to September 2018 (BMH cohort) were selected. Kaplan-Meier curve was used for survival analysis and Log-rank test was performed. Cox proportional risk regression analysis screened the independent risk factors affecting the prognosis of gastric cancer, and established a line graph model. Receiver operating characteristic (ROC) curve and calibration curve were plotted, and area under curve (AUC) was calculated to evaluate the predictive efficiency of the model.

Results

Multivariate Cox analysis of external validation results using validation sets showed that PNI, LVI and TSR were independent prognostic and pathological factors except of pTNM stage, and their occurrence was correlated. The triple positive group (LVI positive, PNI positive, high TSR) and twice positive group (LVI positive, PNI positive, high TSR) showed differences in tumor nature, tumor size, pTNM stage, primary site, and overall survival rate (OS) in pathological grade, including signet ring cell carcinoma, large tumor (≥5 cm), stageⅢ, non-proximal and distal stomach, poorly differentiated and classified as three positive group had the worst prognosis, with 5-year OS of 0, 12.4%, 12.6%, 13.8% and 14.9%, respectively. The nomogram prediction model was established based on pTNM, Sanyang classification, CEA and lymphocyte to monocyte ratio (LMR), the ROC AUC of postoperative OS was 0.744 (95% CI: 0.704-0.784), showing good prediction value.

Conclusions

The prognosis of gastric cancer with positive LVI, positive PNI and high TSR is poor. The established nomogram prediction model based on pTNM, Sanyang classification, CEA and LMR can be used as a supplement for prognosis prediction of tumor-lymphaden-metastasis pathological staging system, which is helpful for postoperative assessment and formulation of treatment plans for patients with gastric cancer.

Key words: Gastric neoplasms, Prognosis, Perineural invasion, Lymphovascular invasion, Tumor stroma ratio

图1 胃癌标本病理切片肿瘤间质比的判定（苏木精-伊红染色×40）　A为低TSR区域挑选；B为低TSR胃癌标注判别示意；C为高TSR区域挑选；D为高TSR胃癌标注判别示意图；红色区域：肿瘤间质；蓝色区域：肿瘤实质；黄色区域：坏死

表1 SGH与BMH队列胃癌一般资料情况比较（例）

队列	SGH队列	BMH队列	统计值	P值
例数	745	131
年龄(岁)			0.197	<0.001
≤45	30	16
>45~60	162	43
>60~75	405	66
>75	148	6
性别			0.956	0.056
男	525	92
女	220	39
肿瘤直径(cm)			0.008	0.822
<5	457	79
≥5	288	52
pTNM分期			0.342	<0.001
Ⅰ	209	10
Ⅱ	182	44
Ⅲ	354	77
T分期			0.184	<0.001
T1	170	4
T2	104	31
T3	185	40
T4	286	56
N分期			0.148	<0.001
N0	281	49
N1	120	28
N2	124	34
N3	220	20
肿瘤位置			0.185	<0.001
近端	178	42
远端	365	45
其他	202	44

表1 SGH与BMH队列胃癌一般资料情况比较（例）

队列	SGH队列	BMH队列	统计值	P值
例数	745	131
年龄(岁)			0.197	<0.001
≤45	30	16
>45~60	162	43
>60~75	405	66
>75	148	6
性别			0.956	0.056
男	525	92
女	220	39
肿瘤直径(cm)			0.008	0.822
<5	457	79
≥5	288	52
pTNM分期			0.342	<0.001
Ⅰ	209	10
Ⅱ	182	44
Ⅲ	354	77
T分期			0.184	<0.001
T1	170	4
T2	104	31
T3	185	40
T4	286	56
N分期			0.148	<0.001
N0	281	49
N1	120	28
N2	124	34
N3	220	20
肿瘤位置			0.185	<0.001
近端	178	42
远端	365	45
其他	202	44

表2 匹配前总体生存率影响因素的单因素和多因素Cox分析

因素	单因素分析			多因素分析
因素	HR	95% CI	P值	HR	95% CI	P值
年龄(岁)
≤45	Ref.
>45~60	0.971	0.488~1.932	0.933
>60~75	1.276	0.673~2.422	0.455
>75	1.798	0.931~3.474	0.081
性别
男	Ref.
女	0.813	0.624~1.058	0.124
pTNM分期
Ⅰ/Ⅱ	Ref.
Ⅲ	3.157	2.449~4.071	<0.001^a	1.708	1.211~2.408	0.002^a
T分期
T1	Ref.
T2	1.863	1.108~3.135	0.019^a
T3	2.881	1.870~4.436	<0.001^a
T4	3.817	2.525~5.772	<0.001^a
N分期
N0	Ref.
N1	1.720	1.120~2.642	0.013^a
N2	3.181	2.181~4.639	<0.001^a
N3	4.498	3.249~6.226	<0.001^a
分化程度
高	Ref.
中	1.217	0.603~2.457	0.584
低	1.449	0.740~2.838	0.279
肿瘤直径(cm)
<5	Ref.
≥5	1.853	1.465~2.344	<0.001^a
病理类型
腺癌	Ref.
印戒细胞癌	1.524	1.068~2.175	0.020^a
其他	0.735	0.377~1.431	0.365
肿瘤位置
近端	Ref.
远端	0.625	0.457~0.854	0.003^a
其他	0.677	0.512~0.896	0.006^a
神经周围浸润(PNI)
阴性	Ref.
阳性	2.975	2.311~3.830	<0.001^a	1.690	1.231~2.320	0.001^a
淋巴脉管浸润(LVI)
阴性	Ref.
阳性	2.726	2.100~3.537	<0.001^a	1.809	1.293~2.531	0.001^a
TSR
高	Ref.
低	2.033	1.592~2.595	<0.001^a	1.753	1.332~2.307	<0.001^a
HER-2
<2+	Ref.
≥2+	1.022	0.771~1.354	0.882
CEA(μg/L)
≤5.0	Ref.
>5.0	2.147	1.603~2.877	<0.001^a	1.843	1.366~2.487	<0.001^a
CA50(U/ml)
≤25	Ref.
>25	1.672	0.965~2.897	0.067
CA125(U/ml)
≤35	Ref.
>35	2.627	1.371~5.035	0.004^a
CA19-9(U/ml)
≤39	Ref.
>39	2.120	1.548~2.905	<0.001^a
CA724(U/ml)
≤6.9	Ref.
>6.9	1.331	0.961~1.844	0.086
NLR
<3.80	Ref.
≥3.80	1.576	1.138~2.182	0.006^a
PLR
< 189.90	Ref.
≥189.90	1.315	1.003~1.725	0.048^a
LMR
< 5.20	Ref.
≥5.20	0.622	0.483~0.803	<0.001^a	0.702	0.527~0.936	0.016^a
SII
< 572.60	Ref.
≥572.60	1.544	1.083~2.202	0.016^a
风险因素
0	Ref.
1	1.097	0.697~0.727	0.688	0.992	0.628~1.565	0.9 71
2	2.309	1.519~3.509	<0.001^a	1.591	1.010~2.505	0.045^a
3	5.912	3.949~8.850	<0.001^a	3.804	2.421~5.976	<0.001^a

表2 匹配前总体生存率影响因素的单因素和多因素Cox分析

因素	单因素分析			多因素分析
因素	HR	95% CI	P值	HR	95% CI	P值
年龄(岁)
≤45	Ref.
>45~60	0.971	0.488~1.932	0.933
>60~75	1.276	0.673~2.422	0.455
>75	1.798	0.931~3.474	0.081
性别
男	Ref.
女	0.813	0.624~1.058	0.124
pTNM分期
Ⅰ/Ⅱ	Ref.
Ⅲ	3.157	2.449~4.071	<0.001^a	1.708	1.211~2.408	0.002^a
T分期
T1	Ref.
T2	1.863	1.108~3.135	0.019^a
T3	2.881	1.870~4.436	<0.001^a
T4	3.817	2.525~5.772	<0.001^a
N分期
N0	Ref.
N1	1.720	1.120~2.642	0.013^a
N2	3.181	2.181~4.639	<0.001^a
N3	4.498	3.249~6.226	<0.001^a
分化程度
高	Ref.
中	1.217	0.603~2.457	0.584
低	1.449	0.740~2.838	0.279
肿瘤直径(cm)
<5	Ref.
≥5	1.853	1.465~2.344	<0.001^a
病理类型
腺癌	Ref.
印戒细胞癌	1.524	1.068~2.175	0.020^a
其他	0.735	0.377~1.431	0.365
肿瘤位置
近端	Ref.
远端	0.625	0.457~0.854	0.003^a
其他	0.677	0.512~0.896	0.006^a
神经周围浸润(PNI)
阴性	Ref.
阳性	2.975	2.311~3.830	<0.001^a	1.690	1.231~2.320	0.001^a
淋巴脉管浸润(LVI)
阴性	Ref.
阳性	2.726	2.100~3.537	<0.001^a	1.809	1.293~2.531	0.001^a
TSR
高	Ref.
低	2.033	1.592~2.595	<0.001^a	1.753	1.332~2.307	<0.001^a
HER-2
<2+	Ref.
≥2+	1.022	0.771~1.354	0.882
CEA(μg/L)
≤5.0	Ref.
>5.0	2.147	1.603~2.877	<0.001^a	1.843	1.366~2.487	<0.001^a
CA50(U/ml)
≤25	Ref.
>25	1.672	0.965~2.897	0.067
CA125(U/ml)
≤35	Ref.
>35	2.627	1.371~5.035	0.004^a
CA19-9(U/ml)
≤39	Ref.
>39	2.120	1.548~2.905	<0.001^a
CA724(U/ml)
≤6.9	Ref.
>6.9	1.331	0.961~1.844	0.086
NLR
<3.80	Ref.
≥3.80	1.576	1.138~2.182	0.006^a
PLR
< 189.90	Ref.
≥189.90	1.315	1.003~1.725	0.048^a
LMR
< 5.20	Ref.
≥5.20	0.622	0.483~0.803	<0.001^a	0.702	0.527~0.936	0.016^a
SII
< 572.60	Ref.
≥572.60	1.544	1.083~2.202	0.016^a
风险因素
0	Ref.
1	1.097	0.697~0.727	0.688	0.992	0.628~1.565	0.9 71
2	2.309	1.519~3.509	<0.001^a	1.591	1.010~2.505	0.045^a
3	5.912	3.949~8.850	<0.001^a	3.804	2.421~5.976	<0.001^a

图2 Kaplan-Meier生存分析曲线　A为SGH队列；B为SGH队列中两阳组

表3 SGH-胃癌队列中三阳组、两阳组、单阳组和三阴组术前血清肿瘤标志物、术前外周血指标及生物标志物水平比较

因素	SGH队列	三阳组	两阳组	单阳组	三阴组	P值
中性粒细胞(×10⁹/L)	3.751(3.626~3.876)	3.609(3.626~3.871)	3.979(3.727~4.230)	3.665(3.431~3.899)	3.712(3.455~3.969)	0.151
单核细胞(×10⁹/L)	0.389(0.377~0.401)	0.394(0.364~0.425)	0.397(0.377~0.416)	0.389(0.367~0.412)	0.372(0.349~0.394)	0.507
淋巴细胞(×10⁹/L)	1.706(1.663~1.749)	1.640(1.547~1.732)	1.708(1.628~1.789)	1.703(1.620~1.787)	1.778(1.686~1.870)	0.233
血小板(×10⁹/L)	229.065(223.027~235.103)	231.463(217.471~245.456)	239.043(227.873~250.213)	219.427(209.101~229.752)	226.097(212.340~239.854)	0.107
CEA(μg/L)^a	7.348(5.573~9.123)	8.428(3.934~12.921)	8.620(5.114~12.126)	5.363(3.362~7.363)	7.171(2.771~11.571)	0.527
CA50(U/ml)^a	13.190(11.280~15.101)	11.075(8.863~13.286)	15.411(10.739~20.083)	12.164(8.512~15.816)	13.797(10.154~17.440)	0.425
CA125(U/ml)^a	13.936(12.572~15.230)	14.758(12.182~17.333)	14.370(12.403~16.337)	13.068(9.906~16.231)	13.784(10.729~16.838)	0.833
CA19-9(U/ml)^a	36.146(26.335~45.956)	43.091(22.457~63.724)	59.231(29.420~89.041)	23.830(13.840~33.819)	17.214(11.794~22.634)	0.010
CA724(U/ml)^a	7.676(5.753~9.560)	10.904(6.076~15.731)	8.494(4.833~12.155)	4.704(1.290~8.119)	7.275(3.609~10.941)	0.158
NLR^a	2.520(2.377~2.663)	2.492(2.232~2.752)	2.670(2.390~3.010)	2.422(2.214~2.630)	2.440(2.068~2.813)	0.472
PLR^a	150.986(144.812~157.161)	162.379(146.985~177.773)	158.280(145.424~171.136)	144.566(134.186~154.947)	137.641(127.658~147.624)	0.024
LMR^a	2.123(4.762~5.069)	4.761(4.438~5.086)	4.684(4.434~4.935)	4.957(4.657~5.256)	5.337(4.966~5.709)	0.023
SII^a	593.487(553.426~633.548)	612.940(522.940~702.938)	656.997(565.738~748.257)	545.609(487.154~604.066)	551.474(473.577~629.370)	0.145

表3 SGH-胃癌队列中三阳组、两阳组、单阳组和三阴组术前血清肿瘤标志物、术前外周血指标及生物标志物水平比较

因素	SGH队列	三阳组	两阳组	单阳组	三阴组	P值
中性粒细胞(×10⁹/L)	3.751(3.626~3.876)	3.609(3.626~3.871)	3.979(3.727~4.230)	3.665(3.431~3.899)	3.712(3.455~3.969)	0.151
单核细胞(×10⁹/L)	0.389(0.377~0.401)	0.394(0.364~0.425)	0.397(0.377~0.416)	0.389(0.367~0.412)	0.372(0.349~0.394)	0.507
淋巴细胞(×10⁹/L)	1.706(1.663~1.749)	1.640(1.547~1.732)	1.708(1.628~1.789)	1.703(1.620~1.787)	1.778(1.686~1.870)	0.233
血小板(×10⁹/L)	229.065(223.027~235.103)	231.463(217.471~245.456)	239.043(227.873~250.213)	219.427(209.101~229.752)	226.097(212.340~239.854)	0.107
CEA(μg/L)^a	7.348(5.573~9.123)	8.428(3.934~12.921)	8.620(5.114~12.126)	5.363(3.362~7.363)	7.171(2.771~11.571)	0.527
CA50(U/ml)^a	13.190(11.280~15.101)	11.075(8.863~13.286)	15.411(10.739~20.083)	12.164(8.512~15.816)	13.797(10.154~17.440)	0.425
CA125(U/ml)^a	13.936(12.572~15.230)	14.758(12.182~17.333)	14.370(12.403~16.337)	13.068(9.906~16.231)	13.784(10.729~16.838)	0.833
CA19-9(U/ml)^a	36.146(26.335~45.956)	43.091(22.457~63.724)	59.231(29.420~89.041)	23.830(13.840~33.819)	17.214(11.794~22.634)	0.010
CA724(U/ml)^a	7.676(5.753~9.560)	10.904(6.076~15.731)	8.494(4.833~12.155)	4.704(1.290~8.119)	7.275(3.609~10.941)	0.158
NLR^a	2.520(2.377~2.663)	2.492(2.232~2.752)	2.670(2.390~3.010)	2.422(2.214~2.630)	2.440(2.068~2.813)	0.472
PLR^a	150.986(144.812~157.161)	162.379(146.985~177.773)	158.280(145.424~171.136)	144.566(134.186~154.947)	137.641(127.658~147.624)	0.024
LMR^a	2.123(4.762~5.069)	4.761(4.438~5.086)	4.684(4.434~4.935)	4.957(4.657~5.256)	5.337(4.966~5.709)	0.023
SII^a	593.487(553.426~633.548)	612.940(522.940~702.938)	656.997(565.738~748.257)	545.609(487.154~604.066)	551.474(473.577~629.370)	0.145

图3 以三阳组与两阳组合并分化程度（A）、病理性质（B）、肿瘤大小（C）、pTNM分期（D）、原发位置（E）为标准对纳入SGH队列的胃癌患者进行Kaplan-Meier总生存期分析

图4 列线图模型预测胃癌5年内生存的ROC曲线　A为列线图模型；B为SGH队列列线图模型和pTNM的5年ROC曲线比较及5年生存概率预测校准曲线；C为BMH队列验证列线图模型和pTNM的5年ROC曲线比较及5年生存概率预测校准曲线

[1]	Thrift AP, El-Serag HB. Burden of gastric cancer[J]. Clin Gastroenterol Hepatol, 2020, 18(3): 534-542.
[2]	Takada K, Yoshida M, Aizawa D, et al. Lymphovascular invasion in early gastric cancer: impact of ancillary D2-40 and elastin staining on interobserver agreement[J]. Histopathology, 2020, 76(6): 888-897.
[3]	Zhang CD, Ning FL, Zeng XT, et al. Lymphovascular invasion as a predictor for lymph node metastasis and a prognostic factor in gastric cancer patients under 70 years of age: A retrospective analysis[J]. Int J Surg, 2018, 53: 214-220.
[4]	Hutchings C, Phillips JA, Djamgoz M. Nerve input to tumours: pathophysiological consequences of a dynamic relationship[J]. Biochim Biophys Acta Rev Cancer, 2020, 1874(2): 188411.
[5]	Tao Q, Zhu W, Zhao X, et al. Perineural invasion and postoperative adjuvant chemotherapy efficacy in patients with gastric cancer[J]. Front Oncol, 2020, 10: 530.
[6]	Mesker WE, Junggeburt JM, Szuhai K, et al. The carcinoma-stromal ratio of colon carcinoma is an independent factor for survival compared to lymph node status and tumor stage[J]. Cell Oncol, 2007, 29(5): 387-398.
[7]	Li T, Yu Z, Yang Y, et al. Rapid multi-dynamic algorithm for gray image analysis of the stroma percentage on colorectal cancer[J]. J Cancer, 2021, 12(15): 4561-4573.
[8]	Pyo JH, Lee H, Min YW, et al. Feasibility of endoscopic resection in early gastric cancer with lymphovascular invasion[J]. Ann Surg Oncol, 2019, 26(2): 449-455.
[9]	Bockman DE, Büchler M, Beger HG. Interaction of pancreatic ductal carcinoma with nerves leads to nerve damage[J]. Gastroenterology, 1994, 107(1): 219-230.
[10]	Liebig C, Ayala G, Wilks JA, et al. Perineural invasion in cancer: A review of the literature[J]. Cancer, 2009, 115(15): 3379-3391.
[11]	Ren T, Zhang W, Li S, et al. Combination of clinical and spectral-CT parameters for predicting lymphovascular and perineural invasion in gastric cancer[J]. Diagn Interv Imaging, 2022, 103(12): 584-593.
[12]	Eriksen AC, Sørensen FB, Lindebjerg J, et al. The prognostic value of tumour stroma ratio and tumour budding in stage Ⅱ colon cancer. A nationwide population-based study[J]. Int J Colorectal Dis, 2018, 33(8): 1115-1124.
[13]	Aurello P, Berardi G, Giulitti D, et al. Tumor-Stroma Ratio is an independent predictor for overall survival and disease free survival in gastric cancer patients[J]. Surgeon, 2017, 15(6): 329-335.
[14]	Abiatari I, DeOliveira T, Kerkadze V, et al. Consensus transcriptome signature of perineural invasion in pancreatic carcinoma[J]. Mol Cancer Ther, 2009, 8(6): 1494-1504.
[15]	Magnon C, Hall SJ, Lin J, et al. Autonomic nerve development contributes to prostate cancer progression[J]. Science, 2013, 341(6142): 1236361.
[16]	Demir IE, Friess H, Ceyhan GO. Nerve-cancer interactions in the stromal biology of pancreatic cancer[J]. Front Physiol, 2012, 3: 97.
[17]	Orecchioni M, Ghosheh Y, Pramod AB, et al. Macrophage polarization: different gene signatures in M1(LPS+) vs. classically and M2(LPS-) vs. alternatively activated macrophages[J]. Front Immunol, 2019, 10: 1084.
[18]	Ohashi M, Kanai F, Ueno H, et al. Adenovirus mediated p53 tumour suppressor gene therapy for human gastric cancer cells in vitro and in vivo[J]. Gut, 1999, 44(3): 366-371.
[19]	Lan KH, Kanai F, Shiratori Y, et al. Tumor-specific gene expression in carcinoembryonic antigen--producing gastric cancer cells using adenovirus vectors[J]. Gastroenterology, 1996, 111(5): 1241-1251.
[20]	Lu J, Dai Y, Xie JW, et al. Combination of lymphovascular invasion and the AJCC TNM staging system improves prediction of prognosis in N0 stage gastric cancer: results from a high-volume institution[J]. BMC Cancer, 2019, 19(1): 216.
[21]	邱佳辉, 蔡谦谦, 杨彦, 等. 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.

[1]	衣晓丽, 胡沙沙, 张彦. HER-2低表达对乳腺癌新辅助治疗疗效及预后的影响[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 340-346.
[2]	施杰, 李云涛, 高海燕. 腋窝淋巴结阳性Luminal A型乳腺癌患者新辅助与辅助化疗的预后及影响因素分析[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 353-361.
[3]	谭巧, 苏小涵, 侯令密, 黎君彦, 邓世山. 乳腺髓样癌的诊治进展[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 366-368.
[4]	杨倩, 李翠芳, 张婉秋. 原发性肝癌自发性破裂出血急诊TACE术后的近远期预后及影响因素分析[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 33-36.
[5]	栗艳松, 冯会敏, 刘明超, 刘泽鹏, 姜秋霞. STIP1在三阴性乳腺癌组织中的表达及临床意义研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 52-56.
[6]	马伟强, 马斌林, 吴中语, 张莹. microRNA在三阴性乳腺癌进展中发挥的作用[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 111-114.
[7]	江振剑, 蒋明, 黄大莉. TK1、Ki67蛋白在分化型甲状腺癌组织中的表达及预后价值研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 623-626.
[8]	晏晴艳, 雍晓梅, 罗洪, 杜敏. 成都地区老年转移性乳腺癌的预后及生存因素研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 636-638.
[9]	莫波, 王佩, 王恒, 何志军, 梁俊, 郝志楠. 腹腔镜胃癌根治术与改良胃癌根治术治疗早期胃癌的疗效[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 644-647.
[10]	鲁鑫, 许佳怡, 刘洋, 杨琴, 鞠雯雯, 徐缨龙. 早期LC术与PTCD续贯LC术治疗急性胆囊炎对患者肝功能及预后的影响比较[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 648-650.
[11]	陈大敏, 曹晓刚, 曹能琦. 肥胖对胃癌患者手术治疗效果的影响研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 651-653.
[12]	姜明, 罗锐, 龙成超. 闭孔疝的诊断与治疗：10年73例患者诊疗经验总结[J]. 中华疝和腹壁外科杂志(电子版), 2023, 17(06): 706-710.
[13]	李永胜, 孙家和, 郭书伟, 卢义康, 刘洪洲. 高龄结直肠癌患者根治术后短期并发症及其影响因素[J]. 中华临床医师杂志(电子版), 2023, 17(9): 962-967.
[14]	王军, 刘鲲鹏, 姚兰, 张华, 魏越, 索利斌, 陈骏, 苗成利, 罗成华. 腹膜后肿瘤切除术中大量输血患者的麻醉管理特点与分析[J]. 中华临床医师杂志(电子版), 2023, 17(08): 844-849.
[15]	索利斌, 刘鲲鹏, 姚兰, 张华, 魏越, 王军, 陈骏, 苗成利, 罗成华. 原发性腹膜后副神经节瘤切除术麻醉管理的特点和分析[J]. 中华临床医师杂志(电子版), 2023, 17(07): 771-776.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

Prognostic value of perineural invasion, lymphovascular invasion combined with tumor stroma ratio in gastric cancer

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

Prognostic value of perineural invasion, lymphovascular invasion combined with tumor stroma ratio in gastric cancer