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

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

Abstract

Abstract:

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

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.

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Figures/Tables 7

References 21

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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

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

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

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

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

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