目的：探讨Cyclin D1与p53的差异表达在眼睑肿瘤诊断与预后中的价值。

方法：采用回顾性研究设计，选取2018年3月至2023年3月于我院行手术切除的眼睑肿瘤患者为研究对象，依据肿瘤性质分为良性组和恶性组。收集两组患者临床资料； 借助GEO数据库获取眼睑肿瘤相关基因数据，运用Sangerbox 3.0平台绘制火山图并完成KEGG富集分析。通过免疫组化检测组织中Cyclin D1、p53和BAX表达水平，采用Spearman分析其与临床特征相关性； 通过Logistic回归分析预后的影响因素。

结果：本研究共纳入眼睑肿瘤患者69例78眼，依据肿瘤性质分为良性组37例41眼和恶性组32例37眼。两组患者组织学分型、TNM分期、有无脉管侵犯、有无分化和有无局部浸润比较均有差异(均P<0.05)。良性肿瘤中，色素痣11眼(27%)、血管瘤9眼(22%)、鳞状细胞乳头状瘤5眼(12%)、表皮样囊肿5眼(12%)、脂溢性角化病4眼(10%)、神经纤维瘤3眼(7%)、钙化上皮瘤和黄色瘤均为2眼(5%)； 恶性肿瘤中，基底细胞癌18眼(49%)、睑板腺癌8眼(22%)、鳞状细胞癌5眼(14%)、皮脂腺癌4眼(11%)、淋巴瘤和恶性黑色素瘤均为1眼(3%)。随访日期截止至2025年3月，良性组患者2 a生存率(95%)明显高于恶性组(78%)(P<0.05)。生物信息学分析共筛选出Cyclin D1、p53和BAX等4 103个差异基因，主要涉及p53信号通路和钙等信号通路。Spearman分析结果显示，局部浸润(r_s=0.71， P<0.05)和TNM期(r_s=0.73， P<0.05)与Cyclin D1相关； 局部浸润(r_s=0.76， P<0.05)和组织学分型(r_s=0.65， P<0.05)与p53相关。Logistic回归结果显示，Cyclin D1、p53、TNM期和局部浸润为预后风险因素。经ROC曲线分析显示，上述四个指标联合检测的预测价值最高(AUC=0.83)。

结论：Cyclin D1和p53高表达可作为眼睑肿瘤良恶性鉴别及预后评估的分子标志物，二者与TNM分期和局部浸润联合检测对预后具有较高预测价值。

METHODS: This retrospective study enrolled patients who underwent surgical resection for eyelid tumors at our hospital between March 2018 and March 2023. Participants were categorized into benign and malignant groups based on tumor characteristics. Clinical data were collected. Genetic data for eyelid tumors were obtained from the GEO database, and differential gene analysis, including volcano plot visualization and KEGG pathway enrichment analysis, was performed using the Sangerbox 3.0 platform. Immunohistochemistry was used to detect the expression levels of Cyclin D1, p53, and BAX in tissue samples. Correlations with clinical features were analyzed using Spearman analysis, and prognostic factors were identified via Logistic regression analysis.

RESULTS: This study included 69 patients with eyelid tumors(78 eyes), categorized into a benign group(37 patients, 41 eyes)and a malignant group(32 patients, 37 eyes)based on tumor characteristics. There were significant differences between the two groups in histological subtype, TNM staging, vascular invasion, differentiation status, and local infiltration(all P<0.05). Among benign tumors: pigmented nevi in 11 eyes(27%), hemangiomas in 9 eyes(22%), squamous cell papillomas in 5 eyes(12%), epidermoid cysts in 5 eyes(12%), seborrheic keratoses in 4 eyes(10%), neurofibromas in 3 eyes(7%), and both calcifying epithelioma and xanthelasma in 2 eyes each(5%); among malignant tumors: basal cell carcinoma in 18 eyes(49%), meibomian gland carcinoma in 8 eyes(22%), squamous cell carcinoma in 5 eyes(14%), sebaceous gland carcinoma in 4 eyes(11%), lymphoma and malignant melanoma each in 1 eye(3%). At the follow-up cutoff date of March 2025, the 2-year survival rate in the benign group(95%)was significantly higher than that in the malignant group(78%; P<0.05). Bioinformatics analysis identified 4 103 differentially expressed genes, including Cyclin D1, p53, and BAX, which were predominantly involved in pathways such as the p53 signaling pathway and calcium-related signaling. Spearman analysis revealed that local invasion(r_s=0.71, P<0.05)and TNM stage(r_s=0.73, P<0.05)correlated with Cyclin D1 expression; local invasion(r_s=0.76, P<0.05)and histological subtype(r_s=0.65, P<0.05)correlated with p53 expression. Logistic regression results indicated that Cyclin D1, p53, TNM staging, and local invasion were prognostic risk factors. ROC curve analysis demonstrated that the combined detection of these four indicators had the highest predictive value for prognosis(AUC=0.83).

CONCLUSION: High expression of cyclin D1 and p53 serves as molecular markers for distinguishing benign from malignant eyelid tumors and assessing prognosis. Combined detection of these markers with TNM staging and local invasion demonstrates high predictive value for prognosis.