Subjects: Medicine, Pharmacy >> Preclinical Medicine submitted time 2023-09-17
Abstract： Objective To study the expression of SMARCA4, BRAF, p53, programmed death receptor 1 (PD-1) and its ligand 1 (PD-L1), and BRAF and neurotrophin tyrosine kinase receptor (NTRK) genes changes in colorectal cancer in Tibet. Methods A total of 64 patients with colorectal cancer resected in Autonomous Region People's Hospital from January 2015 to July 2021 was enrolled in this study. The expression of SMARCA4, BRAF, p53, PD-1, PD-L1 was detected by immunohistochemical(IHC) staining, and detection of NTRK1, NTRK2, NTRK3 fusion gene by fluorescence in situ hybridization (FISH), BRAF V600E gene mutation by polymerase chain reaction (PCR). Results 64 cases of colorectal cancer, with a male to female ratio of 1.21:1 and the mean age of (56.59 ± 13.27) years. 46 cases (46/64, 71.88%) were located in the colon, and 18 cases (18/64, 28.12%) were in the rectum. 60 cases (60/64, 93.75%) were adenocarcinoma, and 4 cases (4/64, 6.25%) were other types. 11 cases (11/64, 17.19%) were in T1 or T2 phase, and 53 cases (53/64, 82.81%) were in T3 or T4 phase; 24 cases (24/64, 37.50%) were found lymph node metastasis. The IHC staining showed that SMARCA41 was partial expression reduced or missing in a case (1/64, 1.56%), BRAF were positive in 4 cases (4/64,6.25%), p53 showed mutant expression pattern in 35 cases (35/64,54.69%). PD-1 expression <10% of tumour background immune cells in 45 cases (45/64,70.31%) , and ≥ 10% in 19 cases（19/64,29.69%）. PD- L1 proportion Score （CPS）<10 in 52 cases(（52/64，81.25%）, and ≥ 10 in 12 cases（12/54,18.75%）.None case was detected the fusion genes of NTRK1, NTRK1, and NTRK1, and four cases were detected BRAF V600E gene mutations. No SMARCA4 gene changes was detected in one case with SMARCA4 partial expression missing. The difference between the PD-L1 expression proportion score and the status of mismatch repair /microsatellite instability (MMR/ MSI), as well as the expression level of PD-1 was statistically significant (P=0.001). Conclusions SMARCA4 expression reduced or missing and NTRK fusion gene are rare in colorectal cancer in Tibet. A few cases have BRAF V600E gene mutations, and Pan-TRK and BRAF expression can be used as initial screening methods for NTRK fusion gene and BRAF gene mutation. Cases with mismatch repair deficiency / microsatellite instability-high (dMMR/MSI-H) are more prone to high expression of PD-L1 protein, and the patients with dMMR/MSI-H may benefit from immunotherapy. The high expression of PD-1 is positively correlated with the high expression of PD-L1.
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