中国医学科学院学报2024，Vol.46Issue(2)：184-192,9.DOI:10.3881/j.issn.1000-503X.15852
西藏地区结直肠癌免疫治疗和靶向治疗相关分子标志物的检测及意义
Detection and Significance of Molecular Markers in Immunotherapy and Targeted Therapy of Colorectal Cancer in Tibet
摘要
Abstract
Objective To study the expression of SWI/SNF-related,matrix-associated,actin-depend-ent regulator of chromatin,subfamily A,member 4(SMARCA4)/Brahma-related gene 1,V-raf murine sarco-ma viral oncogene homolog B(BRAF),P53,programmed cell death protein-1(PD-1),and programmed death-ligand 1(PD-L1),and changes in the expression of BRAF and neurotrophic tyrosine receptor kinase(NTRK)in the patients with colorectal cancer in Tibet,thereby providing a basis for targeted therapy and immunotherapy for this disease in Tibet.Methods A total of 64 patients with colorectal cancer resected in the Tibet Autonomous Region People's Hospital from January 2015 to July 2021 were enrolled in this study.The expression of SMARCA4,BRAF,P53,PD-1,and PD-L1 was detected by immunohistochemical staining.The gene fusion involving NTRK1,NTRK2,and NTRK3 was detected by fluorescence in situ hybridization,and the BRAF V600E gene mutation by polymerase chain reaction.Results The 64 patients with colorectal cancer were at a male-to-female ratio of 1.21∶1,with the mean age of(56.59±13.27)years.The tumors were located in the co-lon in 46(71.88%)patients and in the rectum in 18(28.12%)patients.Sixty(93.75%)patients presented adenocarcinoma,and 4(6.25%)patients presented other types of tumors.The patients in T1/T2 and T3/T4 phases accounted for 17.19%(n =11)and 82.81%(n =53),respectively.Lymph node metastasis occurred in 24(37.50%)patients.The immunohistochemical staining results showed partially down-regulated or absent ex-pression of SMARCA4 in 1(1.56%)patient,positive BRAF expression in 4(6.25%)patients,and mutant expression of P53 in 35(54.69%)patients.The PD-1-expressing tumor associated immune cell was proportion score<10%in 45(70.31%)patients and≥10%in 19(29.69%)patients.The PD-L1 combined positive score was<10 in 52(81.25%)patients and≥10 in 12(18.75%)patients.The gene fusion of NTRK1,NTRK2,and NTRK3 was negative in all the patients,and BRAF V600E gene mutation was positive in 4(6.25%)patients.The SMARCA4 gene alteration was not detected in the patient with partial expression missing of SMARCA4.The PD-L1 combine positive score was correlated with the deficient mismatch repair(dMMR)/mic-rosatellite instability-high(MSI-H)and the PD-1 expression(χ2 = 10.223,P = 0.001;χ2 = 11.979,P = 0.001).Conclusions The down-regulated or absent SMARCA4 expression and NTRK gene fusion are rare in the patients with colorectal cancer in Tibet.A few patients present BRAF V600E gene mutations,and Pan-TRK and BRAF expression can be used for the primary screening of NTRK gene fusion and BRAF gene mutation.The patients with dMMR/MSI-H are prone to high expression of PD-L1 and expected to benefit from immunothera-py.No significant correlation exists between P53 mutation and PD-L1 expression.The high expression of PD-1 is positively correlated with the high expression of PD-L1.关键词
西藏地区/结直肠癌/SWI/SNF相关、基质相关、肌动蛋白依赖性染色质调节因子A亚科成员4/程序性死亡受体1/程序性死亡配体1/V-raf鼠类肉瘤病毒癌基因同源物B/神经营养因子酪氨酸受体激酶分类
医药卫生引用本文复制引用
罗含欢,郭平平,刘斌云,霍真,边巴扎西,王倩,多布啦,尼玛卓玛,达珍,王寒..西藏地区结直肠癌免疫治疗和靶向治疗相关分子标志物的检测及意义[J].中国医学科学院学报,2024,46(2):184-192,9.基金项目
西藏自治区自然科学基金(XZ202101ZR0095G) （XZ202101ZR0095G）
