1.Detection and Significance of Molecular Markers in Immunotherapy and Targeted Therapy of Colorectal Cancer in Tibet
Hanhuan LUO ; Binyun LIU ; Zhen HUO ; BIANbazhaxi ; Qian WANG ; DUObula ; NImazhuoma ; Zhen DA ; Han WANG ; Pingping GUO
Acta Academiae Medicinae Sinicae 2024;46(2):184-192
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.
2.DLG7/DLGAP5 as a potential therapeutic target in gastric cancer.
Kang LI ; Xiangsheng FU ; Ping WU ; Bianba ZHAXI ; Hanhuan LUO ; Qijie LI
Chinese Medical Journal 2022;135(13):1616-1618
3.Expression and Significance of GATA-3, H3K27me3 in Tibetan Patients with Bladder Urothelial Carcinoma
Zhuoma NIMA ; Yu XIAO ; Hanhuan LUO ; Bula DUO ; Han WANG ; Zhen DA ; Jiangcun SILANG ; Pingping GUO ; Ruiqian LIAO
Medical Journal of Peking Union Medical College Hospital 2024;15(4):953-959
To investigate the expression and clinical significance of GATA-3 and H3K27me3 in Tibetan patients with bladder urothelial carcinoma (BUC). BUC and normal bladder tissues were collected retrospectively from January 2016 to December 2021 in the People's Hospital of Tibet Autonomous Region. The expression of GATA-3 and H3K27me3 in both tissues was detected by immunohistochemical method, and the clinical and pathological characteristics were statistically analyzed. A total of 70 patients with BUC were selected, including 51 males and 19 females, with an average age of (60.5±12.0) years. At the same time, 20 normal bladder tissue samples were collected during the same period. All cases were Tibetan patients. Immunohistochemistry results showed that the high expression rate of GATA-3 in BUC and normal bladder tissue was 70.0%(49/70) and 100%(20/20), respectively. High expression of GATA-3 was associated with male, low pathological grade, and non-invasive tissue(all The expression of GATA-3 was down regulated in Tibetan BUC patients, and significantly down regulated with the increase of tumor grade, suggesting that GATA-3 may be involved in the occurrence and development of BUC and related to its malignancy, providing reference for clinical diagnosis and treatment as well as judging disease prognosis. The expression of H3K27me3 in Tibetan BUC patients was higher than that in normal bladder tissue, suggesting that H3K27me3 may be a new immune marker for diagnosis of BUC.