CD68 expression predicts risk of postoperative recurrence in stage IB lung squamous cell carcinoma

doi:10.3877/cma.j.issn.2095-8773.2025.03.04

Abstract

Abstract:

Objective

To investigate the association between stromal CD68⁺ macrophage infiltration and disease-free survival (DFS) in patients with stage ⅠB lung squamous cell carcinoma (LUSC) after surgery, and to evaluate its potential as a prognostic biomarker.

Methods

Sixty patients with stage ⅠB LUSC who underwent surgery in 2014 in Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively analyzed. CD68⁺ macrophages in the tumor stroma were quantified by immunohistochemistry and HALO digital pathology. Based on the optimal cutoff value (12.01) from ROC analysis, patients were divided into high- and low-expression groups. Kaplan-Meier survival analysis and Cox regression models were used to assess DFS and prognostic factors.

Results

After a median follow-up of 82 months, 21 (35%) patients experienced recurrence or metastasis. High CD68 expression was significantly associated with longer DFS (P<0.05). Multivariate Cox regression showed that high CD68 expression was an independent protective factor [hazard ratio (HR) =0.179, 95% confidence interval (CI) : 0.041–0.775, P=0.021], whereas visceral pleural invasion was associated with poorer prognosis (HR=2.865, 95%CI: 1.18–6.95, P=0.018) .

Conclusions

High stromal infiltration of CD68⁺ macrophages is associated with improved DFS in patients with stage ⅠB LUSC. CD68 may serve as a novel prognostic biomarker, and its integration with traditional pathological factors may enhance postoperative risk stratification and personalized treatment.

Key words: Lung squamous cell carcinoma, Stage ⅠB, CD68, Tumor-associated macrophages, Disease-free survival, Prognosis

Qi Cao, Zhiwen Luo, Yun Che. CD68 expression predicts risk of postoperative recurrence in stage IB lung squamous cell carcinoma[J]. Chinese Journal of Thoracic Surgery(Electronic Edition), 2025, 12(03): 144-151.

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Figures/Tables 6

References 16

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参数	例（%）
性别
男	56（93.33）
女	4（6.67）
年龄（岁）
>60	45（75.00）
≤60	15（25.00）
肿瘤部位
上叶	27（45.00）
下叶	27（45.00）
中叶	6（10.00）
大小（cm）
>3	42（70.00）
≤3	18（30.00）
分化
低	14（23.33）
中	41（68.33）
高	5（8.33）
脏层胸膜
侵犯	22（36.67）
未侵犯	38（63.33）
脉管
侵犯	9（15.00）
未侵犯	51（85.00）
神经
侵犯	6（10.00）
未侵犯	54（90.00）
淋巴结清扫
≥16	42（70.00）
<16	18（30.00）
术后辅助治疗
否	46（76.67）
是	14（23.33）

参数	例（%）
性别
男	56（93.33）
女	4（6.67）
年龄（岁）
>60	45（75.00）
≤60	15（25.00）
肿瘤部位
上叶	27（45.00）
下叶	27（45.00）
中叶	6（10.00）
大小（cm）
>3	42（70.00）
≤3	18（30.00）
分化
低	14（23.33）
中	41（68.33）
高	5（8.33）
脏层胸膜
侵犯	22（36.67）
未侵犯	38（63.33）
脉管
侵犯	9（15.00）
未侵犯	51（85.00）
神经
侵犯	6（10.00）
未侵犯	54（90.00）
淋巴结清扫
≥16	42（70.00）
<16	18（30.00）
术后辅助治疗
否	46（76.67）
是	14（23.33）

变量	单因素分析		多因素分析
变量	HR（95%CI）	P值	HR（95%CI）	P值
性别
男
女	0.606（0.141~2.603）	0.500
年龄（岁）
>60岁
≤60	1.147（0.42~3.134）	0.789
肿瘤部位
上叶
下叶	0.92（0.365~2.318）	0.185
中叶	2.51（0.667~9.441）	0.173
大小（cm）
>3
≤3	1.047（0.406~2.7）	0.924
分化
低
中	1.501（0.5~4.502）	0.469
高	0.641（0.072~5.748）	0.691
脏层胸膜
侵犯
未侵犯	2.766（1.166~6.56）	0.021	2.865（1.197~6.856）	0.018
脉管
侵犯
未侵犯	1.85（0.616~5.56）	0.273
神经
侵犯
未侵犯	2.001（0.67~5.976）	0.214
淋巴结清扫
≥16
<16	1.322（0.512~3.41）	0.564
术后治疗
否
是	1.101（0.403~3.009）	0.852
CD68
≥12.01%
<12.01%	0.185（0.043~0.797）	0.023	0.179（0.041~0.775）	0.021

变量	单因素分析		多因素分析
变量	HR（95%CI）	P值	HR（95%CI）	P值
性别
男
女	0.606（0.141~2.603）	0.500
年龄（岁）
>60岁
≤60	1.147（0.42~3.134）	0.789
肿瘤部位
上叶
下叶	0.92（0.365~2.318）	0.185
中叶	2.51（0.667~9.441）	0.173
大小（cm）
>3
≤3	1.047（0.406~2.7）	0.924
分化
低
中	1.501（0.5~4.502）	0.469
高	0.641（0.072~5.748）	0.691
脏层胸膜
侵犯
未侵犯	2.766（1.166~6.56）	0.021	2.865（1.197~6.856）	0.018
脉管
侵犯
未侵犯	1.85（0.616~5.56）	0.273
神经
侵犯
未侵犯	2.001（0.67~5.976）	0.214
淋巴结清扫
≥16
<16	1.322（0.512~3.41）	0.564
术后治疗
否
是	1.101（0.403~3.009）	0.852
CD68
≥12.01%
<12.01%	0.185（0.043~0.797）	0.023	0.179（0.041~0.775）	0.021

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