非小细胞肺癌组织DCLK1 和Bmi-1 蛋白表达及其与三维适形放疗效果的相关性研究

目的 探讨非小细胞肺癌(non small cell lung cancer，NSCLC)组织双肾上腺素样激酶1(dou-blecortin-likekinase 1，DCLK1)、B 细胞特异性莫洛氏鼠白血病病毒插入位点一(B cell specific moloney leukemia virus insert site-1，Bmi-1)蛋白表达及其与三维适形放疗效果的关系。方法 选取2018 年6 月～ 2021 年1 月江南大学附属医院收治的102 例拟行三维适形放疗的NSCLC 患者和40 例肺错构瘤患者，分别记为恶性组和良性组。采用免疫组织化学法检测二组病灶组织DCLK1 和Bmi-1 蛋白表达，并对比两组病灶组织及恶性组中不同临床病理特征患者癌组织DCLK1和Bmi-1 蛋白阳性表达率。恶性组均予以三维适形放疗6 周，并评价其放疗效果。对比恶性组三维适形放疗无效与放疗有效患者癌组织DCLK1 和Bmi-1 蛋白阳性表达率，采用Logistic 多元回归分析探讨恶性组NSCLC 组织DCLK1 和Bmi-1 蛋白阳性表达与三维适形放疗效果的关系。结果 恶性组病灶组织DCLK1 阳性表达率(60.78% )和Bmi-1 蛋白阳性表达率(70.59%)均高于良性组(32.50%，35.00%)，差异具有统计学意义(χ2=9.224，15.241，均P ＜ 0.05)；临床Ⅲ～Ⅳ期、未/ 低分化、淋巴结转移患者的DCLK1 和Bmi-1 蛋白阳性表达率分别高于临床Ⅰ～Ⅱ期、高/ 中分化、无淋巴结转移患者，差异均有统计学意义(χ2=6.638，9.756，5.670；7.724，7.447，6.114，均P ＜ 0.05)；三维适形放疗有效率为67.65%，无效率为32.35%；临床分期Ⅲ～Ⅳ期(OR=5.414，95%CI=4.027~6.663)、未/ 低分化(OR=4.773，95%CI=3.156~5.974)、淋巴结转移(OR=5.307，95%CI=3.768~6.626)、癌组织DCLK1(OR=5.496，95%CI=3.967~6.882)和Bmi-1 蛋白(OR=5.624，95%CI=4.127~7.287)阳性表达均是恶性组三维适形放疗无效的危险因素(均P ＜ 0.05)。结论 NSCLC 组织DCLK1 和Bmi-1 蛋白阳性表达率高于肺良性肿瘤，且临床分期、分化程度、淋巴结转移、NSCLC 组织DCLK1 和Bmi-1 蛋白阳性表达均可影响NSCLC 患者三维适形放疗的效果。

Expressions of DCLK1 and Bmi-1 Proteins in Non-small Cell Lung Cancer Tissues and Their Relationship with the Effect of Three-dimensional Conformal Radiotherapy

Objective To investigate the expressions of dou-blecortin-like kinase 1 (DCLK1) and B cell specific moloney leukemia virus insert site-1 (Bmi-1) proteins in non small cell lung cancer (NSCLC) tissue and their relationship with the effect of three-dimensional conformal radiotherapy. Methods 102 NSCLC patients who were treated by three-dimensional conformal radiotherapy and 40 pulmonary hamartoma patients in Affiliated Hospital of Jiangnan University were selected from June 2018 to January 2021, and were recorded as malignant group and benign group respectively. Immunohistochemical method was used to detect the expressions of DCLK1 and Bmi-1 proteins in the two groups of lesion tissues, and the positive expression rates of DCLK1 and Bmi-1 proteins were compared between the two groups of lesion tissues and cancer tissues of patients with different clinicopathological features in malignant group. The malignant group was received three-dimensional conformal radiotherapy for 6 weeks, and the radiotherapy effect was evaluated. The positive expression rates of DCLK1 and Bmi-1 proteins in cancer tissues of patients with ineffective and effective three-dimensional conformal radiotherapy in malignant group were compared. Logistic multiple regression analysis was used to explore the relationship between the positive expressions of DCLK1 and Bmi-1 proteins in malignant group NSCLC tissue and the effect of three-dimensional conformal radiotherapy. Results The positive rates of DCLK1 (60.78%) and Bmi-1(70.59%) protein expressions in the lesions of the malignant group were higher than those in the benign group(32.50%，35.00%), the differences were statistically significant (χ2=9.224, 15.241，all P ＜ 0.05). The positive rates of DCLK1 and Bmi-1 protein expressions in patients with clinical stage III ～ IV, undifferentiated/poorly differentiated, and lymph node metastasis were respectively higher than clinical stage Ⅰ ～ Ⅱ , high/moderately differentiated patients without lymph node metastasis with statistically(χ2=6.638, 9.756, 5.670；7.724, 7.447, 6.114, all P ＜ 0.05). Three-dimensional conformal radiotherapy had an effective rate of 67.65% and an ineffective rate of 32.35%. Clinical stage Ⅲ～Ⅳ(OR=5.414, 95%CI=4.027~6.663), undifferentiated/poorly differentiated(OR=4.773, 95%CI=3.156~5.974), lymph node Metastasis (OR=5.307, 95%CI=3.768~6.626) and the positive expressions of DCLK1(OR=5.496, 95%CI=3.967~6.882)and Bmi-1 (OR=5.624, 95%CI=4.127~7.287)proteins in cancer tissues were risk factors for the ineffectiveness of three-dimensional conformal radiotherapy in the malignant group (all P ＜ 0.05). Conclusion The positive expression rates of DCLK1 and Bmi-1 proteins in NSCLC was higher than that in benign lung tumors. The clinical stage, degree of differentiation, lymph node metastasis and the positive expressions of DCLK1 and Bmi-1 proteins in NSCLC could affect the effect of three-dimensional conformal radiotherapy in NSCLC patients.