CTCs_PCNA_ANX...与临床病理特征和预后的关系_王传.pdf

CTCs PCNA ANXA2 在 NSCLC 患者中的表达及与临床病理特征和预后的关系王传顾晓静史金英夏静荣陈洁基金项目:河北省卫生厅课题(编号:20181018)作者单位:050000河北石家庄石家庄市人民医院呼吸内科 摘要目的分析循环肿瘤细胞(CTCs)、增殖细胞核抗原(PCNA)、膜联蛋白 A2(ANXA2)水平在非小细胞肺癌(NSCLC)患者中的变化，并探讨其与 NSCLC 患者不同临床病理特征和预后的关系。方法选取 2015 年 1 月至 2016 年 6 月期间石家庄市人民医院呼吸内科收治的 NSCLC 患者115 例作为癌症组，100 例肺部良性病变患者作为良性组，收集同期体检中心健康体检者 100 例作为对照组，回顾性分析 3 组研究对象的临床资料，比较 CTCs、PCNA、ANXA2 在 3 组研究对象间表达的差异，通过每周电话随访的方式对患者进行定期随访，记录 NSCLC 患者 50 个月的生存情况。利用 Cox 回归分析影响 NSCLC 患者预后的独立危险因素，采用 Kaplan Meier 法进行生存分析。结果癌症组患者 CTCs、PCNA、ANXA2 水平明显高于良性组和对照组，良性组高于对照组，差异均有统计学意义(P 0 05)。以肺癌的病理切片结果为金标准，CTCs、PCNA、ANXA2 诊断肺癌的受试者工作特征(OC)曲线显示，三者联合检测诊断肺癌的曲线下面积是 0 958，灵敏度 92 0%，特异度 94 6%。根据不同病理特征进行单因素分析，CTCs、PCNA、ANXA2 在有吸烟史、肿瘤直径5 cm、TNM 分期为 期、分化程度为低分化、有淋巴结转移、有远处转移的患者中明显升高，差异有统计学意义(P 0 05)。据 Pearson 相关性分析可知 CTCs、PCNA、ANXA2 与 NSCLC 患者的肿瘤直径(r=0 602、0 543、0 743)、TNM 分期(r=0 238、0 307、0 342)、淋巴结转移(r=0 391、0 387、0 421)、远处转移(r=0 296、0 274、0 198)呈正相关，与分化程度(r=0 334、0 372、0 403)呈负相关(P 0 05)。Cox 回归分析结果显示，TNM 分期、分化程度、淋巴结转移、远处转移以及 CTCs、PCNA、ANXA2 阳性表达是 NSCLC 患者预后不良的独立危险因素(P 0 05)。Kaplan Meier 生存曲线显示 CTCs、PC-NA、ANXA2 高水平表达与 NSCLC 患者生存期密切相关。结论CTCs、PCNA、ANXA2 在 NSCLC 患者中明显升高，且与不同临床病理特征密切相关，是预后不良的独立危险因素，联合检测有助于疾病早期诊断及预后判断。关键词 非小细胞肺癌;循环肿瘤细胞;增殖细胞核抗原;膜联蛋白 A2;临床病理特征;预后doi:10.3969/j.issn.1000 0399.2023.03.004Expression of CTCs PCNA and ANXA2 in NSCLC patients and their relationship with clinicopathological features and prognosisWANG Chuan，GU Xiaojing，SHI Jinying，XIA Jingrong，CHEN JieDepartment of espiratory Medicine，Shijiazhuang People s Hospital，Shijiazhuang 050000，ChinaFunding project:Health Department of Hebei Province(No 20181018)Abstract ObjectiveTo analyze the changes of circulating tumor cell(CTCs)，proliferating nuclear antigen(PCNA)，and annexprotein A2(ANXA2)levels in patients with non small cell lung cancer(NSCLC)，and to explore the relationship between CTCs and differ-ent clinicopathologic features and prognosis of NSCLC patients MethodsA total of 115 NSCLC patients admitted to the espiratory Depart-ment of Shijiazhuang People s Hospital from January 2015 to June 2016 were selected as the cancer group，100 patients with benign lung le-sions were selected as the benign group，and 100 healthy patients from the Physical Examination Center during the same period were collectedas the control group The clinical data of the three groups of subjects were retrospectively analyzed The differences in the expression ofCTCs，PCNA，and ANXA2 of the three groups were compared，and the patients were followed up regularly through weekly telephone follow up to record the survival of NSCLC patients for 50 months Cox regression was used to analyze the independent risk factors affecting the prog-nosis of NSCLC patients，and Kaplan Meier method was used for survival analysis esultsThe levels of CTCs，PCNA and ANXA2 incancer group were significantly higher than those in benign group and control group，and those in benign group were higher than those in con-trol group，with statistical significance(P 0 05)Taking the results of lung cancer pathological sections as the gold standard，the subjectwork curve of CTCs，PCNA and ANXA2 for the diagnosis of lung cancer showed that the area under the curve of the combined detection ofCTCS，PCNA and ANXA2 was 0 958，the sensitivity was 92 0%，and the specificity was 94 6%According to univariate analysis based ondifferent pathological features，CTCs，PCNA and ANXA2 significantly increased in patients with smoking history，tumor diameter 5 cm，TNM stage ，low differentiation，lymph node metastasis or distant metastasis，and the difference was statistically significant(P 262安徽医学第 44 卷第 3 期Anhui Medical Journal2023 年 3 月0 05)Pearson correlation analysis showed that CTCs，PCNA，ANXA2 and NSCLC patients had tumor diameter(r=0 602，r=0 543，r=0743)，TNM stage(r=0 238，r=0 307，r=0 342)，lymph node metastasis(r=0 391，r=0 387，r=0 421)and distant metastasis(r=0 296，r=0 274，r=0 198)were positively correlated with the degree of differentiation(r=0 334，r=0 372，r=0 403)(P 0 05)Cox regression analysis showed that TNM stage，differentiation degree，lymph node metastasis，distant metastasis，and positiveexpression of CTCs，PCNA，and ANXA2 were independent risk factors for poor prognosis in NSCLC patients Kaplan meier survival curveshowed that high levels of CTCs，PCNA and ANXA2 were closely related to the survival of NSCLC patients ConclusionsCTCs，PCNA andANXA2 significantly increase in NSCLC patients，which are closely related to different clinicopathological features and are independent riskfactors for poor prognosis Combined detection is helpful for early diagnosis and prognosis Key wordsNon small cell lung cancer;Circulating tumor cell;Proliferating nuclear antigen;Annexin A2;Clinicopathologicalfeatures;Prognosis肺癌是全球发病率最高的恶性肿瘤，也是癌症死亡的第一大原因1。随着环境污染的加剧、人口老龄化加快、不良生活习惯等多重因素共同作用，肺癌发病率和致死率急剧上升，而且随年龄增加而呈上升趋势2。肺癌常见亚型主要以非小细胞肺癌(Non small cell lung cancer，NSCLC)和小细胞肺癌为主，其中 NSCLC 占比 85%以上3。NSCLC 患者早期症状不明显，就诊时多已发展到中晚期，错失手术机会而导致生存率低、预后差。因此，寻找 NSCLC 患者早期诊断以及预后评估的血清学指标对提高患者治愈率、改善预后具有重要意义。循环肿瘤细胞(circulating tumorcell，CTCs)是从病灶直接脱落