Ⅰ、Ⅱ期宫颈癌患者术后T细胞亚群变化特征及与术后淋巴结转移的关系

doi:10.3760/cma.j.cn371439-20240704-00037

摘要/Abstract

摘要：

目的探究国际妇产科联盟（FIGO）分期（2014）Ⅰ、Ⅱ期宫颈癌患者术后T细胞亚群变化特征及与术后淋巴结转移的关系。方法选择2018年11月至2020年11月于四川省岳池县人民医院和四川大学华西广安医院接受宫颈癌根治术及盆腔淋巴结清扫术治疗的FIGO分期为ⅠA、ⅠB1、ⅠB2、ⅡA1期的192例宫颈癌患者进行研究，根据FIGO分期的不同将患者分为Ⅰ期组（n=85）和Ⅱ期组（n=107）；比较不同FIGO分期患者手术前、后T细胞亚群动态变化；采用重复测量方差分析不同分期患者治疗期间T细胞亚群水平；采用logistic回归分析宫颈癌患者术后淋巴结转移的影响因素；采用多因素logistic回归分析患者T细胞亚群与术后淋巴结转移的关系；采用受试者操作特征（ROC）曲线分析T细胞水平对患者术后淋巴结转移的预测效能。结果 Ⅱ期患者术后淋巴结转移率[32.71%（35/107）]高于Ⅰ期患者[14.12%（12/85）]，差异具有统计学意义（χ²=8.86，P=0.003）。与Ⅱ期组相比，术前1 dⅠ期组患者的CD3⁺、CD4⁺ T细胞水平和CD4⁺/CD8⁺比值均明显更高（均P<0.001），CD8⁺ T细胞水平明显更低（P<0.001）。术后不同阶段，患者CD3⁺、CD4⁺、CD8⁺ T细胞水平和CD4⁺/CD8⁺比值呈动态变化，术后1、7、30 d时，Ⅰ期组患者的CD3⁺、CD4⁺ T细胞水平和CD4⁺/CD8⁺比值均高于Ⅱ期组患者（均P<0.001），CD8⁺ T细胞水平均低于Ⅱ期组患者（均P<0.001）。两组患者T细胞亚群CD3⁺、CD4⁺、CD8⁺、CD4⁺/CD8⁺比值时间效应、组间效应、交互效应方面差异均具有统计学意义（均P<0.001）。单因素分析显示，病理类型（OR=1.85，95%CI为1.14~2.33，P=0.015）、分化程度（OR=1.93，95%CI为1.18~2.67，P=0.024）、肌层浸润深度（OR=2.08，95%CI为1.26~2.59，P=0.012）、肿瘤形态（OR=2.17，95%CI为1.57~2.63，P=0.009）、宫旁浸润（OR=1.95，95%CI为1.43~2.76，P=0.036）、淋巴血管间隙侵犯（OR=2.03，95%CI为1.28~2.57，P=0.021）均是FIGO分期Ⅰ期和Ⅱ期宫颈癌患者术后淋巴结转移的影响因素。多因素分析显示，分化程度（OR=1.75，95%CI为1.08~2.03，P=0.015）、肌层浸润深度（OR=2.30，95%CI为1.43~2.84，P=0.021）、宫旁浸润（OR=2.50，95%CI为1.76~2.97，P=0.018）、淋巴血管间隙侵犯（OR=1.96，95%CI为1.03~2.51，P=0.033）均是FIGO分期Ⅰ期和Ⅱ期宫颈癌患者术后淋巴结转移的独立影响因素。多因素logistic回归分析显示，Ⅰ期和Ⅱ期宫颈癌患者术前1 d的CD3⁺、CD4⁺、CD8⁺ T细胞水平和CD4⁺/CD8⁺比值均是术后淋巴结转移的独立影响因素（均P<0.05）。ROC曲线分析显示，术前1 d的Ⅰ期患者CD3⁺、CD4⁺、CD8⁺ T细胞水平和CD4⁺/CD8⁺比值预测术后淋巴结转移的曲线下面积分别为0.86、0.82、0.83、0.89，Ⅱ期分别为0.90、0.93、0.87、0.95，CD4⁺/CD8⁺比值预测患者术后淋巴结转移的预测效能明显高于其他指标（均P<0.001）。结论 FIGO分期Ⅰ期和Ⅱ期宫颈癌患者手术治疗后1~30 d，其体内CD3⁺、CD4⁺ T细胞水平及CD4⁺/CD8⁺比值较治疗前均明显升高，而CD8⁺ T细胞水平则明显降低，且T细胞亚群与患者手术后淋巴结转移间具有明显相关性。此外，分化程度为低分化、肌层浸润深度≥1/2、宫旁浸润、淋巴血管间隙侵犯均是术后淋巴结转移的独立危险因素。

关键词: 宫颈肿瘤, T淋巴细胞亚群, 淋巴转移

Abstract:

Objective To investigate the changes of T lymphocyte subsets in patients with stage Ⅰ and Ⅱ cervical cancer after surgery and their relationship with postoperative lymph node metastasis according to the International Federation of Gynecology and Obstetrics （FIGO） stage （2014）. Methods A total of 192 patients with FIGO stage ⅠA，ⅠB1，ⅠB2 and ⅡA1 who received radical cervical cancer resection and pelvic lymph node dissection in People's Hospital of Yuechi County of Sichuan Province and West China Guang'an Hospital of Sichuan University from November 2018 to November 2020 were selected for this study. According to FIGO stage，patients were divided into stage Ⅰ group （n=85） and stage Ⅱ group （n=107）. The dynamic changes of T lymphocytes subsets in patients with different FIGO stages were compared before and after surgery. Repeated measurement of variance was used to analyze the levels of T lymphocytes subsets in patients of different stages during treatment. Logistic regression was used to analyze the influencing factors of postoperative lymph node metastasis in patients with cervical cancer. Multivariate logistic regression was used to analyze the relationship between T lymphocytes subsets and postoperative lymph node metastasis. Receiver operator characteristic （ROC） curve was used to analyze the predictive efficacy of T lymphocytes level in postoperative lymph node metastasis. Results The postoperative lymph node metastasis rate in stage Ⅱ patients [32.71% （35/107）] was higher than that in stage Ⅰ patients [14.12% （12/85）]，with a statistically significant difference （χ²=8.86，P=0.003）. Compared with the stage Ⅱ group，the levels of CD3⁺，CD4⁺ T lymphocytes and CD4⁺/CD8⁺ ratio were significantly higher in the stage Ⅰ group 1 day before surgery （all P<0.001），and the level of CD8⁺ T lymphocytes was significantly lower （P<0.001）. The levels of CD3⁺，CD4⁺，CD8⁺ T lymphocytes and the ratio of CD4⁺/CD8⁺ showed dynamic changes at different stages after surgery. On 1，7 and 30 days after surgery，the levels of CD3⁺，CD4⁺ T lymphocytes and the ratio of CD4⁺/CD8⁺ in stage Ⅰ group were higher than those in stage Ⅱ group （all P<0.001），CD8⁺ T cell levels were lower than those in stage Ⅱ group （all P<0.001）. There were statistically significant differences in T lymphocytes subsets CD3⁺，CD4⁺，CD8⁺ and CD4⁺/CD8⁺ time effect，intergroup effect and interaction effect between the two groups （all P<0.001）. Univariate analysis showed that the pathological type （OR=1.85，95%CI：1.14-2.33，P=0.015），differentiation degree （OR=1.93，95%CI：1.18-2.67，P=0.024），depth of myometrial invasion （OR=2.08，95%CI：1.26-2.59，P=0.012），tumor morphology （OR=2.17，95%CI：1.57-2.63，P=0.009），parametrial invasion （OR=1.95，95%CI：1.43-2.76，P=0.036） and lymphovascular space invasion （OR=2.03，95%CI：1.28-2.57，P=0.021） were the influencing factors for postoperative lymph node metastasis in patients with FIGO stage Ⅰ and Ⅱ cervical cancer. Multivariate analysis showed that the degree of differentiation （OR=1.75，95%CI：1.08-2.03，P=0.015），depth of myometrial invasion （OR=2.30，95%CI：1.43-2.84，P=0.021），parametrial invasion （OR=2.50，95%CI：1.76-2.97，P=0.018） and lymphovascular space invasion （OR=1.96，95%CI：1.03-2.51，P=0.033） were independent factors for postoperative lymph node metastasis in patients with FIGO stage Ⅰ and Ⅱ cervical cancer. Multivariate logistic regression analysis showed that the levels of CD3⁺，CD4⁺，CD8⁺ T cells and the ratio of CD4⁺/CD8⁺ in patients with stage Ⅰ and stage Ⅱ cervical cancer 1 day before surgery were independent influencing factors for postoperative lymph node metastasis （all P<0.05）. ROC curve analysis showed that the areas under the curve of CD3⁺，CD4⁺，CD8⁺ T lymphocytes levels and the ratio of CD4⁺/CD8⁺ in stage Ⅰ patients 1 day before surgery for predicting postoperative lymph node metastasis were 0.86，0.82，0.83，0.89，respectively，and those in stage Ⅱ patients were 0.90，0.93，0.87，0.95，respectively. CD4⁺/CD8⁺ ratio was significantly more effective in predicting postoperative lymph node metastasis than other indexes （all P<0.001）. Conclusions The levels of CD3⁺，CD4⁺ T lymphocytes，and the CD4⁺/CD8⁺ ratio in patients with FIGO stage Ⅰ and Ⅱ cervical cancer are significantly higher in 1-30 days after surgery than before，while the level of CD8⁺ T lymphocytes is significantly lower than before. There is a significant correlation between T lymphocytes subsets and lymph node metastasis after surgery. In addition，low differentiation，depth of myometrial invasion ≥1/2，parametrial invasion，and lymphovascular space invasion are independent risk factors for postoperative lymph node metastasis.

Key words: Uterine cervical neoplasms, T-lymphocytes subsets, Lymphatic metastasis

周晓宇, 蒲雪峰, 龙树林, 李露, 何文英. Ⅰ、Ⅱ期宫颈癌患者术后T细胞亚群变化特征及与术后淋巴结转移的关系[J]. 国际肿瘤学杂志, 2025, 52(4): 224-230.

Zhou Xiaoyu, Pu Xuefeng, Long Shulin, Li Lu, He Wenying. Changes of T lymphocyte subsets and the relationship with postoperative lymph node metastasis in patients with stage Ⅰ and Ⅱ cervical cancer[J]. Journal of International Oncology, 2025, 52(4): 224-230.

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临床资料	Ⅰ期组（n=85）	Ⅱ期组（n=107）	χ²值	P值	临床资料	Ⅰ期组（n=85）	Ⅱ期组（n=107）	χ²值	P值
年龄（岁）					肿瘤形态
<45	42（49.41）	50（46.73）	0.14	0.712	结节型	20（23.53）	29（27.10）
≥45	43（50.59）	57（53.27）	0.14	0.712	菜花型	62（72.94）	72（67.29）	0.89	0.641
绝经					溃疡型	3（3.53）	6（5.61）
是	25（29.41）	35（32.71）	0.24	0.624	宫旁浸润
否	60（70.59）	72（67.29）	0.24	0.624	有	8（9.41）	14（13.08）	0.63	0.428
HPV感染					无	77（90.59）	93（86.92）	0.63	0.428
有	58（68.24）	76（71.03）	0.18	0.675	淋巴血管间隙侵犯
无	27（31.76）	31（28.97）	0.18	0.675	有	10（11.76）	14（13.08）	0.08	0.784
病理类型					无	75（88.24）	93（85.92）	0.08	0.784
鳞状细胞癌	75（88.24）	90（84.11）	0.67	0.414	神经侵犯
非鳞状细胞癌	10（11.76）	17（15.89）	0.67	0.414	有	52（61.18）	69（64.49）	0.22	0.637
分化程度					无	33（38.82）	38（35.51）	0.22	0.637
低分化	20（23.53）	22（20.56）			术后淋巴结转移
中分化	50（58.82）	64（59.81）	0.30	0.862	是	12（14.12）	35（32.71）	8.86	0.003
高分化	15（17.65）	21（19.63）			否	73（85.88）	72（67.29）	8.86	0.003
肌层浸润深度
<1/2	32（37.65）	37（34.58）	0.19	0.659
≥1/2	53（62.35）	70（65.42）	0.19	0.659

组别	CD3⁺ T细胞（%）						CD4⁺ T细胞（%）
组别	术前1 d	术后1 d	术后7 d	术后30 d	F值	P值	术前1 d	术后1 d	术后7 d	术后30 d	F值	P值
Ⅰ期组（n=85）	64.39±5.59	68.18±5.26^a	74.65±5.33^ab	82.13±5.81^abc	170.06	<0.001	31.26±3.77	33.82±4.18^a	37.86±4.57^ab	42.38±5.06^abc	102.86	<0.001
Ⅱ期组（n=107）	55.32±5.07	61.34±5.11^a	68.72±5.41^ab	78.12±5.76^abc	362.10	<0.001	25.14±3.14	27.96±4.09^a	32.77±4.46^ab	39.14±4.97^abc	225.92	<0.001
t值	11.77	9.09	7.59	4.77			12.27	9.77	7.77	4.45
P值	<0.001	<0.001	<0.001	<0.001			<0.001	<0.001	<0.001	<0.001
组别	CD8⁺ T细胞（%）						CD4⁺/CD8⁺比值
组别	术前1 d	术后1 d	术后7 d	术后30 d	F值	P值	术前1 d	术后1 d	术后7 d	术后30 d	F值	P值
Ⅰ期组（n=85）	22.32±2.88	20.14±2.28^a	18.95±1.74^ab	18.06±1.15^abc	64.77	<0.001	1.56±0.12	1.62±0.15^a	1.73±0.16^ab	1.95±0.17^abc	109.74	<0.001
Ⅱ期组（n=107）	27.51±2.62	24.15±2.26^a	21.75±1.76^ab	19.83±1.17^abc	285.44	<0.001	1.26±0.09	1.36±0.18^a	1.51±0.15^ab	1.74±0.16^abc	210.42	<0.001
t值	13.05	12.16	11.01	10.49			19.79	10.69	9.80	8.77
P值	<0.001	<0.001	<0.001	<0.001			<0.001	<0.001	<0.001	<0.001

变量	β值	SE值	Wald χ²值	OR值（95%CI）	P值
Ⅰ期
CD3⁺ T细胞	-0.657	0.279	5.53	0.52（0.30~0.90）	0.019
CD4⁺ T细胞	-0.482	0.228	4.46	0.62（0.40~0.97）	0.035
CD8⁺ T细胞	-1.068	0.309	11.96	0.34（0.19~0.63）	0.001
CD4⁺/CD8⁺比值	-0.701	0.247	8.06	0.50（0.31~0.81）	0.005
Ⅱ期
CD3⁺ T细胞	-0.601	0.226	7.10	0.55（0.35~0.85）	0.008
CD4⁺ T细胞	-0.712	0.261	7.43	0.49（0.29~0.82）	0.006
CD8⁺ T细胞	-0.650	0.269	5.86	0.52（0.31~0.88）	0.016
CD4⁺/CD8⁺比值	-0.455	0.225	4.10	0.64（0.41~0.99）	0.043

指标	CD3⁺ T细胞	CD4⁺ T细胞	CD8⁺ T细胞	CD4⁺/CD8⁺比值
Ⅰ期
AUC（95%CI）	0.86（0.63~0.98）^a	0.82（0.71~0.93）^b	0.83（0.70~0.97）^c	0.89（0.71~0.97）
敏感性	0.539	0.739	0.653	0.749
特异性	0.472	0.663	0.731	0.712
Ⅱ期
AUC（95%CI）	0.90（0.73~0.94）^d	0.93（0.75~0.96）^e	0.87（0.70~0.89）^f	0.95（0.63~0.97）
敏感性	0.594	0.625	0.514	0.808
特异性	0.611	0.702	0.844	0.623