PD-1、PD-L1在铂耐药卵巢上皮性癌组织中的表达及其临床意义

翟欣影; 王丽华; 李艳华

doi:10.16766/j.cnki.issn.1674-4152.003545

PD-1、PD-L1在铂耐药卵巢上皮性癌组织中的表达及其临床意义

doi: 10.16766/j.cnki.issn.1674-4152.003545

蚌埠医科大学第一附属医院肿瘤妇科，安徽蚌埠 233004

基金项目:

安徽高校自然科学研究项目 KJ2021A0720

详细信息

通讯作者:
李艳华，E-mail：bblyh1964@126.com

中图分类号: R737.31 R730.43
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出版历程
- 收稿日期: 2023-08-14
- 网络出版日期: 2024-07-22

Expression of PD-1 and PD-L1 in platinum-resistant ovarian epithelial carcinoma and their clinical significance

Department of Gynaecologic Oncology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui 233004, China

摘要

摘要: 目的探讨程序性死亡受体1(PD-1)、程序性死亡受体配体1(PD-L1)在铂耐药卵巢上皮性癌患者组织中的表达情况, 分析铂耐药卵巢上皮性癌患者PD-1、PD-L1表达与临床特征及预后的关系。方法收集2018年1月—2021年6月于蚌埠医科大学第一附属医院接受手术治疗的111例卵巢癌患者组织蜡块(71例铂耐药组蜡块和40例铂敏感组蜡块)，另取10例卵巢良性组织蜡块作为对照。采用ELiVision ^TM免疫组化法检测样本中PD-1、PD-L1表达水平，分析两者表达与患者病理特征和预后的关系。结果 PD-1、PD-L1在铂敏感组和铂耐药组阳性率分别为22.5%、32.5%和42.3%、53.5%，铂耐药组中PD-1、PD-L1阳性率高于铂敏感组(P＜0.05)；PD-1、PD-L1在浆液性癌和非浆液性癌组织中阳性表达率分别为50.0%、61.5%和21.1%、31.6%，PD-1、PD-L1在手术病理分期Ⅲ~Ⅳ期和Ⅰ~Ⅱ期患者中阳性表达率分别为51.0%、63.3%和22.7%、31.8%，非浆液性、Ⅰ~Ⅱ期患者PD-1、PD-L1表达低于浆液性癌和Ⅲ~Ⅳ期患者(P＜0.05)；多因素Cox比例风险模型结果显示，PD-1阳性(HR=3.905，P=0.001)、PD-L1阳性(HR=4.581, P=0.002)、手术病理分期为Ⅲ~Ⅳ期(HR=3.948，P=0.026)是铂耐药卵巢上皮性癌患者预后的独立危险因素；生存分析显示PD-1、PD-L1阳性患者两年累积生存率明显低于其他表达情况(P＜0.05)。结论卵巢上皮性癌组织中PD-1、PD-L1高表达与耐药有关，从而导致肿瘤的恶性进展和生存时间的缩短，是患者预后不良的标志之一。
- 上皮性卵巢癌 /
- 程序性死亡受体－配体1 /
- 铂耐药 /
- 化疗耐药 /
- 免疫治疗 /
- 程序性死亡受体1
Abstract: Objective To investigate the expression of programmed death receptor 1 (PD-1) and programmed death receptor-ligand 1 (PD-L1) in the tissues of patients with platinum-resistant ovarian epithelial cancer, and to analyze the relationship between the expression of PD-1 and PD-L1 in patients with platinum-resistant ovarian epithelial cancer and clinical characteristics and prognosis. Methods The tissue paraffin blocks of 111 patients with ovarian cancer (71 cases of platinum-resistant tissue paraffin blocks and 40 cases of platinum-sensitive tissue paraffin blocks) who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical University from January 2018 to June 2021 were collected, and 10 cases of benign ovarian tissue paraffin blocks were taken as controls. The expression levels of PD-1 and PD-L1 in ovarian cancer tissues were detected by ELiVision^TM immunohistochemistry method, and the relationships between the expression levels and pathological features and prognosis were analyzed. Results The positive rates of PD-1 and PD-L1 in the platinum-sensitive group and platinum-resistant group were 22.5%, 32.5% and 42.3%, 53.5%, respectively. The positive rates of PD-1 and PD-L1 in the drug-resistant group were higher than those in the platinum-sensitive group (P < 0.05). The positive expression rates of PD-1 and PD-L1 in serous and non-serous cancer tissues were 50.0%, 61.5% and 21.1%, 31.6%, respectively. The positive expression rates of PD-1 and PD-L1 in surgical pathological stage Ⅲ-Ⅳ and Ⅰ-Ⅱ were 51.0%, 63.3 %, and 22.7%, 31.8%, respectively. The expressions of PD-1 and PD-L1 were significantly lower than those in serous carcinoma and stage Ⅲ to Ⅳ patients, with statistical significance (P < 0.05). The multifactorial Cox proportional risk model shows: PD-1 positive group (HR=3.905, P=0.001), PD-L1 positive group (HR=4.581, P=0.002), surgical pathological stage Ⅲ and Ⅳ stages (HR=3.948, P=0.026) were independent risk prognostic factors affecting survival of patients with platinum-resistant ovarian epithelial cancer. Survival analysis showed that the two-year survival rate of PD-1 and PD-L1 positive patients were lower than that of negative patients (P < 0.05). Conclusion The high expression of PD-1 and PD-L1 in ovarian epithelial carcinoma tissues is related to drug resistance, which leads to malignant progression of tumor and shortened survival time, and is one of the indicators of poor prognosis of patients.
- Epithelial ovarian cancer /
- Programmed death receptor-ligand 1 /
- Platinum resistance /
- Chemotherapy resistance /
- Immunotherapy /
- Programmed death receptor 1

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图 1 PD-1和PD-L1在卵巢癌组织及卵巢良性组织中的表达(EnVision^TM免疫组化法, ×200)

Figure 1. Expression of PD-1 and PD-L1 in ovarian cancer tissues and benign ovarian tissues (EnVisionTM immunohistochemistry, ×200)

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图 2 PD-1表达情况对铂耐药卵巢上皮性癌患者预后的影响

Figure 2. Effect of expression of PD-1 on prognosis of patients with platinum-resistant epithelial ovarian cancer

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图 3 PD-L1表达情况对铂耐药卵巢上皮性癌患者预后的影响

Figure 3. Effect of expression of PD-L1 on prognosis of patients with platinum-resistant epithelial ovarian cancer

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图 4 PD-1联合PD-L1表达情况对铂耐药卵巢上皮性癌患者预后的影响

Figure 4. Effect of expression of PD-1 combined with PD-L1 on prognosis of patients with platinum-resistant epithelial ovarian cancer

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表 1 2组卵巢上皮性癌患者PD-1、PD-L1阳性率比较[例(%)]

Table 1. Comparison of the positive rates of PD-1 and PD-L1 in two groups of ovarian epithelial carcinoma patients[cases (%)]

组别	例数	PD-1		PD-L1
组别	例数	阴性	阳性	阴性	阳性
铂敏感组	40	31(77.5)	9(22.5)	27(67.5)	13(32.5)
铂耐药组	71	41(57.7)	30(42.3)	33(46.5)	38(53.5)
χ²值		4.318		4.552
P值		0.036		0.033

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表 2 不同临床病理特征铂耐药卵巢上皮性癌患者PD-1、PD-L1表达情况比较[例(%)]

Table 2. Comparison of expression of PD-1 and PD-L1 in patients with platinum-resistant epithelial ovarian cancer with different clinicopathological features[cases (%)]

临床资料	例数	PD-1		χ²值	P值	PD-L1		χ²值	P值
临床资料	例数	阴性	阳性	χ²值	P值	阴性	阳性	χ²值	P值
年龄				2.427	0.119			0.244	0.621
＜55岁	43	28(65.1)	15(34.9)			21(48.8)	22(51.2)
≥55岁	28	13(46.4)	15(53.6)			12(42.9)	16(57.1)
病理类型				4.779	0.029			5.021	0.025
非浆液性	19	15(78.9)	4(21.1)			13(68.4)	6(31.6)
浆液性	52	26(50.0)	26(50.0)			20(38.5)	32(61.5)
腹水				0.053	0.817			0.174	0.676
无	32	18(56.3)	14(43.7)			14(43.7)	18(56.3)
有	39	23(59.0)	16(41.0)			19(48.7)	20(51.3)
FIGO分期				4.981	0.026			6.036	0.014
Ⅰ~Ⅱ	22	17(77.3)	5(22.7)			15(68.2)	7(31.8)
Ⅲ~Ⅳ	49	24(49.0)	25(51.0)			18(36.7)	31(63.3)
原发部位				0.352	0.553			2.071	0.150
单侧	21	11(52.4)	10(47.6)			7(33.3)	14(66.7)
双侧	50	30(60.0)	20(40.0)			26(52.0)	24(48.0)
绝经状态				0.099	0.753			0.001	0.979
否	13	7(53.8)	6(46.2)			6(46.2)	7(53.8)
是	58	34(58.6)	24(41.4)			27(46.6)	31(53.4)

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表 3 铂耐药卵巢上皮性癌患者预后影响因素的单因素Cox回归分析

Table 3. Univariate Cox regression analysis of prognostic factors in patients with platinum-resistant epithelial ovarian cancer

变量	B	SE	Waldχ²	P值	HR(95% CI)
年龄≥55岁	0.343	0.357	0.925	0.336	1.409(0.700~2.836)
病理类型为浆液性	1.173	0.535	4.811	0.028	3.233(1.133~9.224)
腹水	0.131	0.357	0.134	0.715	1.139(0.566~2.293)
FIGO分期为Ⅲ~Ⅳ期	1.849	0.611	9.157	0.002	6.351(1.918~21.032)
原发部位为双侧	-0.412	0.373	1.219	0.270	0.662(0.319~1.376)
绝经	0.111	0.488	0.051	0.821	1.117(0.429~2.905)
PD-1阳性	1.552	0.385	16.245	＜0.001	4.722(2.220~10.045)
PD-L1阳性	1.756	0.458	14.684	＜0.001	5.791(2.359~14.220)
注：各变量赋值如下，年龄≥55岁=1，＜55岁=0；病理类型为浆液性=1，非浆液性=0；有腹水=1，无腹水=0；FIGO分期Ⅲ~Ⅳ期=1，Ⅰ~Ⅱ期=0，肿瘤原发部位为双侧=1，单侧=0；绝经=1，未绝经=0；PD-1，阳性=1，阴性=0；PD-L1，阳性=1，阴性=0。

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表 4 铂耐药卵巢上皮性癌患者预后影响因素的多因素Cox回归分析

Table 4. Multivariate Cox regression analysis of prognostic factors in patients with platinum-resistant epithelial ovarian cancer

变量	B	SE	Waldχ²	P值	HR(95% CI)
病理类型为浆液性	0.100	0.604	0.028	0.868	1.106(0.338~3.611)
FIGO分期为Ⅲ~Ⅳ期	1.373	0.617	4.947	0.026	3.948(1.177~13.243)
PD-1阳性	1.362	0.409	11.115	0.001	3.905(1.753~8.699)
PD-L1阳性	1.522	0.501	9.226	0.002	4.581(1.716~12.232)
注：各变量赋值如下，病理类型为非浆液性=1，浆液性=2；FIGO分期Ⅰ~Ⅱ期=1，Ⅲ~Ⅳ期=2；PD-1，阴性=0，阳性=1；PD-L1，阴性=0，阳性=1。

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表 5 不同PD-1、PD-L1表达情况铂耐药卵巢上皮性癌患者总生存率比较

Table 5. Comparison of overall survival rate of patients with platinum-resistant epithelial ovarian cancer with different expressions of PD-1 and PD-L1

项目	例数	总生存率(%)		log-rank χ²值	P值
项目	例数	1年	2年	log-rank χ²值	P值
PD-1				20.208	＜0.001
阴性	41	97.6	82.9
阳性	30	90.0	40.0
PD-L1				19.133	＜0.001
阴性	33	100.0	87.9
阳性	38	89.5	44.7
PD-1+PD-L1				37.356	＜0.001
双阴性	22	100.0	100.0
PD-1阳性+PD-L1阴性	11	100.0	63.6
PD-1阴性+PD-L1阳性	19	94.7	63.2
双阳性	19	84.2	26.3

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