Predictive value of tertiary lymphoid structures in the prognosis of patients with gastric neuroendocrine neoplasms

doi:10.3877/cma.j.issn.1674-3946.2024.04.014

Abstract

Abstract:

Objective

To investigate the characteristics and prognostic value of tertiary lymphoid structures (TLS) in gastric neuroendocrine neoplasms (g-NEN) and to construct and validate a prognostic nomogram.

Methods

We retrospectively collected the clinical data from 140 patients with g-NEN at Nanjing Drum Tower Hospital from 2013 to 2021. We firstly analyzed the characteristics of TLS by HE&immunohistochemical staining and then univariate and multivariate Cox analysis using SPSS 22.0 software was performed to derive independent risk factors; Lastly, we constructed a nomogram and validated its efficacy by using R studio.

Results

The median age of the 140 g-NEN patients was 62.5 (51, 69.25) years; 84 (60%) were male and 56 (40%) were female; the median of TLS density was 0.0694 cells per mm² (0.01585, 0.19775); 64 (45.7%) were g-NET, 76 (54.3%) were g-NEC/g-MiNEN; TNM stage Ⅰ/Ⅱ was 80 (57.1%), 60 (42.9%) was Ⅲ/Ⅳ, vascular invasion was 56 (40%), and neurological invasion was 47 (33.6%). TLS were mainly located in the tumor margin or stroma region and have three different mature shapes. TLS density, WHO classification and TNM stage were independent prognostic factors (P<0.05). The nomogram has high degree of discrimination, calibration and clinical practicability.

Conclusion

The TLS density is an independent prognostic factor of g-NEN and the nomogram incorporating TLS density has good predictive performance and clinical application.

Key words: Gastric Neuroendocrine Neoplasms, Tertiary Lymphoid Structures, Clinicopathological Features, Prognosis, Nomogram

Daming Cai, Xiaofeng Lu, Xingzhou Wang, Meng Wang, Song Liu, Xuefeng Xia, Xiaofei Shen, Junfeng Du, Wenxian Guan. Predictive value of tertiary lymphoid structures in the prognosis of patients with gastric neuroendocrine neoplasms[J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2024, 18(04): 401-405.

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https://zhpwkssxzz.cma-cmc.com.cn/EN/Y2024/V18/I04/401

Figures/Tables 7

References 18

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临床资料	类别	例（%）	临床资料	类别	例（%）
性别	男	84 (60.0)	WHO分类	g-NET	64（45.7）
性别	女	56 (40.0)	WHO分类	g-NEC	76（54.3）
T分期	T₁	62 (44.3)	血管侵犯	无	84（60.0）
	T₂	13 (9.3)	血管侵犯	有	56（40.0）
	T₃	54 (38.6)	神经侵犯	无	93（66.4）
	T₄	11 (7.9)	神经侵犯	有	47（33.6）
N分期	N₀	79 (56.4)		中位数	62.5
N分期	N₁₊	61 (43.6)	年龄(岁)	四分位距	(51, 69.25)
M分期	M₀	135（96.4）	TLS密度（个/mm²）	中位数四分位距	0.0694(0.01585, 0.19775)
	M₁	5（3.6）	TLS密度（个/mm²）	中位数四分位距	0.0694(0.01585, 0.19775)
TNM分期	I/II	80（57.1）
TNM分期	III/IV	60（42.9）

临床资料	类别	例（%）	临床资料	类别	例（%）
性别	男	84 (60.0)	WHO分类	g-NET	64（45.7）
性别	女	56 (40.0)	WHO分类	g-NEC	76（54.3）
T分期	T₁	62 (44.3)	血管侵犯	无	84（60.0）
	T₂	13 (9.3)	血管侵犯	有	56（40.0）
	T₃	54 (38.6)	神经侵犯	无	93（66.4）
	T₄	11 (7.9)	神经侵犯	有	47（33.6）
N分期	N₀	79 (56.4)		中位数	62.5
N分期	N₁₊	61 (43.6)	年龄(岁)	四分位距	(51, 69.25)
M分期	M₀	135（96.4）	TLS密度（个/mm²）	中位数四分位距	0.0694(0.01585, 0.19775)
	M₁	5（3.6）	TLS密度（个/mm²）	中位数四分位距	0.0694(0.01585, 0.19775)
TNM分期	I/II	80（57.1）
TNM分期	III/IV	60（42.9）

临床病理特征	例数	单因素		多因素
临床病理特征	例数	Hazard ratio (95% CI)	P值	Hazard ratio (95% CI)	P值
年龄	140	1.058(1.031-1.086)	<0.001	0.990(0.958-1.023)	0.542
性别	140		<0.001
男	84	Reference		Reference
女	56	0.352(0.184-0.672)	0.002	0.550(0.281-1.078)	0.081
TLS密度	140	0.000(0.000-0.000)	<0.001	0.000(0.000-0.036)	0.004
TNM分期	140		<0.001
I/II	80	Reference		Reference
III/IV	60	16.351(7.298-36.631)	<0.001	3.292(1.406-7.712)	0.006
WHO分类	140		<0.001
g-NET	64	Reference		Reference
g-NEC	76	76.214(10.498-553.292)	<0.001	9.658(1.126-82.812)	0.039
血管侵犯	140		<0.001
无	84	Reference		Reference
有	56	9.499(4.893-18.442)	<0.001	1.778(0.733-4.315)	0.203
神经侵犯	140		<0.001
无	93	Reference		Reference
有	47	7.320(4.065-13.183)	<0.001	1.023(0.478-2.187)	0.954

临床病理特征	例数	单因素		多因素
临床病理特征	例数	Hazard ratio (95% CI)	P值	Hazard ratio (95% CI)	P值
年龄	140	1.058(1.031-1.086)	<0.001	0.990(0.958-1.023)	0.542
性别	140		<0.001
男	84	Reference		Reference
女	56	0.352(0.184-0.672)	0.002	0.550(0.281-1.078)	0.081
TLS密度	140	0.000(0.000-0.000)	<0.001	0.000(0.000-0.036)	0.004
TNM分期	140		<0.001
I/II	80	Reference		Reference
III/IV	60	16.351(7.298-36.631)	<0.001	3.292(1.406-7.712)	0.006
WHO分类	140		<0.001
g-NET	64	Reference		Reference
g-NEC	76	76.214(10.498-553.292)	<0.001	9.658(1.126-82.812)	0.039
血管侵犯	140		<0.001
无	84	Reference		Reference
有	56	9.499(4.893-18.442)	<0.001	1.778(0.733-4.315)	0.203
神经侵犯	140		<0.001
无	93	Reference		Reference
有	47	7.320(4.065-13.183)	<0.001	1.023(0.478-2.187)	0.954

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