血浆游离甲氧基肾上腺类物质与嗜铬细胞瘤和副神经节瘤SDHB表型的相关性

doi:10.3969/j.issn.1004-583X.2026.06.009

摘要/Abstract

摘要：

目的探讨血浆游离甲氧基肾上腺类物质(metanephrines, MNs)与嗜铬细胞瘤和副神经节瘤(pheochromocytoma and paraganglioma, PPGL)琥珀酸脱氢酶B(succinate dehydrogenase Subunit B, SDHB)表型的相关性。方法选取2021年3月至2025年3月于本院接受治疗的190例PPGL患者作为研究组进行研究,另选取同期在本院进行体检且各项指标均正常的100例健康人群作为对照组。收集两组基线资料,采用高效液相色谱-串联质谱法检测两组甲氧基肾上腺素(metanephrine, MN)和甲氧基去甲肾上腺素(normetanephrine, NMN)水平,采用免疫组化EnVision两步法检测研究组SDHB蛋白表达情况,分析MN、NMN水平与SDHB表型(缺失/阳性)的相关性及其与临床病理特征的关联。结果研究组血浆MN、NMN水平均显著高于对照组(P<0.05)。190例PPGL患者中,SDHB缺失68例(35.79%),其中副神经节瘤(paraganglioma, PGL)占比83.82%(57/68),显著高于嗜铬细胞瘤(pheochromocytoma, PCC)(16.18%,11/68)(P<0.05)。SDHB缺失组血浆NMN水平(7.53±1.95) nmol/L显著高于SDHB阳性组(5.19±1.26) nmol/L(P<0.05),而MN水平在两组间差异无统计学意义(P>0.05)。SDHB缺失与年龄、高血压、肿瘤部位、肿瘤类型、血管浸润、Ki-67增殖指数、转移情况及血浆NMN水平存在一定的相关性(P<0.05)。结论血浆NMN水平与PPGL的SDHB表型密切相关,SDHB缺失更常见于PGL,且SDHB缺失患者常伴随NMN水平升高,同时与年龄、高血压、肿瘤部位、肿瘤类型、血管浸润、Ki-67增殖指数及转移情况等不良临床病理特征显著相关。

关键词: 嗜铬细胞瘤, 副神经节瘤, 游离甲氧基肾上腺类物质, SDHB表型, 相关性

Abstract:

Objective To investigate the association between plasma free metanephrines (MNs) and the succinate dehydrogenase subunit B (SDHB) phenotype in pheochromocytoma and paraganglioma (PPGL). Methods A total of 190 patients with PPGL treated at our hospital from March 2021 to March 2025 were enrolled as the study group. In addition, 100 healthy individuals who underwent physical examination at the same hospital during the same period and had normal results were selected as the control group. Baseline data were collected for both groups. Plasma metanephrine (MN) and normetanephrine (NMN) levels were measured using high-performance liquid chromatography-tandem mass spectrometry. SDHB protein expression in the study group was detected by immunohistochemical EnVision two-step method. The correlation between MN/NMN levels and the SDHB phenotype (loss/positive) was analyzed, along with their associations with clinicopathological characteristics. Results Plasma MN and NMN levels were significantly higher in the study group than in the control group (P<0.05). Among the 190 patients with PPGL, SDHB loss was observed in 68 cases (35.79%), of which paraganglioma (PGL) accounted for 83.82% (57/68), significantly higher than pheochromocytoma (PCC) (16.18%, 11/68) (P<0.05). The plasma NMN level in the SDHB-loss group was significantly higher than that in the SDHB-positive group ([7.53±1.95] nmol/L vs [5.19±1.26] nmol/L, P<0.05), whereas no statistically significant difference in MN level was found between the two groups (P>0.05). SDHB loss was associated with age, hypertension, tumor location, tumor type, vascular invasion, Ki-67 proliferation index, metastasis, and plasma NMN level (P<0.05). Conclusion Plasma NMN level is closely associated with the SDHB phenotype in PPGL. SDHB loss is more common in PGL, and patients with SDHB loss often have elevated NMN levels. SDHB loss is also significantly associated with adverse clinicopathological features, including age, hypertension, tumor location, tumor type, vascular invasion, Ki-67 proliferation index, and metastasis.

Key words: pheochromocytoma, paraganglioma, free metanephrines, SDHB phenotype, correlation

中图分类号:

王丽阳, 向丹丹, 丁冉. 血浆游离甲氧基肾上腺类物质与嗜铬细胞瘤和副神经节瘤SDHB表型的相关性[J]. 临床荟萃, 2026, 41(6): 534-538.

Wang Liyang, Xiang Dandan, Ding Ran. Association between plasma free metanephrines and the SDHB phenotype in pheochromocytoma and paraganglioma[J]. Clinical Focus, 2026, 41(6): 534-538.

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链接本文: https://www.lchc.cn/CN/10.3969/j.issn.1004-583X.2026.06.009

https://www.lchc.cn/CN/Y2026/V41/I6/534

图/表 3

参考文献 19

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组别	例数	NMN	MN
研究组	190	6.03±1.90	0.57±0.22
对照组	100	0.53±0.15	0.18±0.09
t值		28.877	16.984
P值		<0.01	<0.01

组别	例数	NMN	MN
研究组	190	6.03±1.90	0.57±0.22
对照组	100	0.53±0.15	0.18±0.09
t值		28.877	16.984
P值		<0.01	<0.01

组别	例数			年龄(岁)[例(%)]					性别[例(%)]				高血压[例(%)]					肿瘤大小(cm)[例(%)]					肿瘤部位[例(%)]
组别	例数			≤55		>55			男		女		是			否		<3			≥3		肾上腺内			肾上腺外
SDHB缺失	68			45(66.18)		23(33.82)			41(60.29)		27(39.71)		40(58.82)			28(41.18)		26(38.24)			42(61.76)		15(22.06)			53(77.94)
SDHB阳性	122			52(42.62)		70(57.38)			66(54.10)		56(45.90)		47(38.52)			75(61.48)		53(43.44)			69(56.56)		65(53.28)			57(46.72)
χ²/t值				9.694					0.681				7.248					0.487					17.458
P值				0.002					0.409				0.007					0.485					<0.01
组别		肿瘤数目[例(%)]						肿瘤类型[例(%)]				肿瘤细胞形态[例(%)]					血管浸润[例(%)]					包膜浸润[例(%)]
组别		单发			多发			PGL		PCC		规则			异型		是			否		是			否
SDHB缺失		35(51.47)			33(48.53)			57(83.82)		11(16.18)		46(67.65)			22(32.35)		38(55.88)			30(44.12)		32(47.06)			36(52.94)
SDHB阳性		78(63.93)			44(36.07)			74(60.66)		48(39.34)		88(72.13)			34(27.87)		31(25.41)			91(74.59)		28(22.95)			94(77.05)
χ²/t值		2.814						10.946				0.422					17.531					11.745
P值		0.093						0.001				0.516					<0.01					0.001
组别			Ki-67增殖指数[例(%)]								转移情况[例(%)]								NMN(nmol/L)					MN(nmol/L)
组别			<3%				≥3%				是			否					NMN(nmol/L)					MN(nmol/L)
SDHB缺失			20(29.41)				48(70.59)				16(23.53)			52(76.47)					7.53±1.95					0.61±0.23
SDHB阳性			85(69.67)				37(30.33)				9(7.38)			113(92.62)					5.19±1.26					0.56±0.20
χ²/t值			28.627								9.969								10.029					1.565
P值			<0.01								0.002								<0.01					0.119

组别	例数			年龄(岁)[例(%)]					性别[例(%)]				高血压[例(%)]					肿瘤大小(cm)[例(%)]					肿瘤部位[例(%)]
组别	例数			≤55		>55			男		女		是			否		<3			≥3		肾上腺内			肾上腺外
SDHB缺失	68			45(66.18)		23(33.82)			41(60.29)		27(39.71)		40(58.82)			28(41.18)		26(38.24)			42(61.76)		15(22.06)			53(77.94)
SDHB阳性	122			52(42.62)		70(57.38)			66(54.10)		56(45.90)		47(38.52)			75(61.48)		53(43.44)			69(56.56)		65(53.28)			57(46.72)
χ²/t值				9.694					0.681				7.248					0.487					17.458
P值				0.002					0.409				0.007					0.485					<0.01
组别		肿瘤数目[例(%)]						肿瘤类型[例(%)]				肿瘤细胞形态[例(%)]					血管浸润[例(%)]					包膜浸润[例(%)]
组别		单发			多发			PGL		PCC		规则			异型		是			否		是			否
SDHB缺失		35(51.47)			33(48.53)			57(83.82)		11(16.18)		46(67.65)			22(32.35)		38(55.88)			30(44.12)		32(47.06)			36(52.94)
SDHB阳性		78(63.93)			44(36.07)			74(60.66)		48(39.34)		88(72.13)			34(27.87)		31(25.41)			91(74.59)		28(22.95)			94(77.05)
χ²/t值		2.814						10.946				0.422					17.531					11.745
P值		0.093						0.001				0.516					<0.01					0.001
组别			Ki-67增殖指数[例(%)]								转移情况[例(%)]								NMN(nmol/L)					MN(nmol/L)
组别			<3%				≥3%				是			否					NMN(nmol/L)					MN(nmol/L)
SDHB缺失			20(29.41)				48(70.59)				16(23.53)			52(76.47)					7.53±1.95					0.61±0.23
SDHB阳性			85(69.67)				37(30.33)				9(7.38)			113(92.62)					5.19±1.26					0.56±0.20
χ²/t值			28.627								9.969								10.029					1.565
P值			<0.01								0.002								<0.01					0.119

指标	回归系数	标准误	Waldχ²值	P值	OR值	95%CI
指标	回归系数	标准误	Waldχ²值	P值	OR值	下限	上限
年龄	1.285	0.553	5.398	0.020	3.616	1.223	10.694
高血压	1.095	0.527	4.314	0.038	2.988	1.064	8.394
肿瘤部位	1.341	0.546	6.025	0.014	3.824	1.310	11.158
肿瘤类型	1.543	0.598	6.650	0.010	4.680	1.448	15.123
血管浸润	1.076	0.508	4.490	0.034	2.933	1.084	7.935
包膜浸润	0.349	0.530	0.433	0.510	1.418	0.501	4.009
Ki-67增殖指数	1.839	0.532	11.952	0.001	6.292	2.218	17.850
转移情况	2.722	0.801	11.548	0.001	15.216	3.165	73.151
NMN	1.050	0.200	27.556	<0.01	2.858	1.931	4.230
常量	-12.162	1.873	42.158	<0.01	<0.001	-	-