Changes of T lymphocyte subsets and the relationship with postoperative lymph node metastasis in patients with stage Ⅰ and Ⅱ cervical cancer

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

Abstract

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

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.

Figures/Tables 6

References 20

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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

指标	时间效应		组间效应		交互效应
指标	F值	P值	F值	P值	F值	P值
CD3⁺ T细胞	25.87	<0.001	10.36	<0.001	10.40	<0.001
CD4⁺ T细胞	25.50	<0.001	14.13	<0.001	10.76	<0.001
CD8⁺ T细胞	16.76	<0.001	11.40	<0.001	12.17	<0.001
CD4⁺/CD8⁺比值	24.59	<0.001	15.17	<0.001	11.31	<0.001

变量	单因素分析			多因素分析
变量	OR值	95%CI	P值	OR值	95%CI	P值
年龄	1.39	0.75~1.79	0.574	1.08	0.67~1.36	0.433
绝经	1.26	0.97~1.58	0.136	1.16	0.88~1.53	0.275
HPV感染	1.43	0.85~1.86	0.239	1.34	0.69~1.93	0.316
病理类型	1.85	1.14~2.33	0.015	1.29	0.95~1.67	0.174
分化程度	1.93	1.18~2.67	0.024	1.75	1.08~2.03	0.015
肌层浸润深度	2.08	1.26~2.59	0.012	2.30	1.43~2.84	0.021
肿瘤形态	2.17	1.57~2.63	0.009	2.18	0.75~2.43	0.106
宫旁浸润	1.95	1.43~2.76	0.036	2.50	1.76~2.97	0.018
淋巴血管间隙侵犯	2.03	1.28~2.57	0.021	1.96	1.03~2.51	0.033
神经侵犯	1.96	0.63~2.35	0.073	1.84	0.91~2.80	0.195

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