Effects of histone acetyltransferase MYST2 on pancreatic cancer
10.3760/cma.j.cn311367-20210222-00110
- VernacularTitle:组蛋白乙酰转移酶MYST2对胰腺癌的影响
- Author:
Wenzhen HAO
1
;
Yunlu FENG
;
Xi WU
;
Shengyu ZHANG
;
Qingwei JIANG
;
Qiang WANG
;
Tao GUO
;
Dongsheng WU
;
Dong WU
;
Aiming YANG
Author Information
1. 中国医学科学院 北京协和医学院疑难重症及罕见病国家重点实验室 100730
- Keywords:
Pancreatic neoplasms;
Histone acetyltransferases;
MYST2;
Phenotype
- From:
Chinese Journal of Digestion
2021;41(8):561-567
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the expression at protein level and diagnostic value of histone acetyltransferase MYST2 in pancreatic cancer.Methods:From December 1st, 2017 to June 30th, 2020, at Peking Union Medical College Hospital, a total of 54 cases of pancreatic cancer tissues and corresponding paracancerous pancreatic tissues (>5 cm from the surgical margin) resected and confirmed by pathology were collected. ASPC1 and BXPC3 pancreatic cancer cell lines were knocked down (ASPC1 and BXPC3 knockdown group), CFPAC1 and SW1990 pancreatic cancer cell lines were overexpressed (CFPAC1 and SW1990 overexpression group), the untreated ASPC1, BXPC3, CFPAC1 and SW1990 were set as blank vector control group. The expression at protein level of MYST2 was detected by Western blotting in patients with different degrees of pathological differentiation, human normal pancreatic duct epithelial cell line HPDE, human pancreatic cancer cell lines ASPC1, BXPC3, CFPAC1 and SW1990, knockdown group, overexpression group and blank vector control group. The cell proliferation, migration, invasion and colony formation ability of the knockdown group, overexpression group and blank vector control group were determined by real-time cellular analysis, Transwell migration and invasion test, and plate colony formation assay. MYST2 immunohistochemical scoring was performed on pancreatic cancer tissues and para cancer tissues. Receiver operating characteristic curve was drawn to analyze the value of different MYST2 protein expression levels in the diagnosis of pancreatic cancer. Independent sample t test and variance analysis were used for statistical analysis. Results:Among the pathological slides of 54 cases of pancreatic cancer, 13 cases were highly differentiated, 24 cases were moderately differentiated, 15 cases were poorly differentiated and 2 cases were undifferentiated, the MYST2 expression at protein level in pancreatic cancer cells was 3.12±1.67, 2.87±1.59, 2.12±1.03 and 1.08±0.34, respectively, and the difference was statistically significant ( F=1.241, P<0.05). The MYST2 expression levels of ASPC1, BXPC3, CFPAC1 and SW1990 were all higher than that of normal pancreatic ductal epithelial cell lines HPDE (1.41±0.47, 1.40±0.93, 1.13±0.62 and 1.71±0.46 vs. 0.82±0.25), and the differences were statistically significant( t=1.625, 1.577, 1.319 and 1.832, all P<0.05). The MYST2 expression level of BXPC3 knockdown group was lower than that of BXPC3 blank vector control group (0.39±0.12 vs. 0.75±0.34); that of ASPC1 knockdown group was lower than that of ASPC1 blank vector control group (0.43±0.22 vs. 0.82±0.48); that of CFPAC1 overexpression group was higher than that of CFPAC1 blank vector control group (1.38±0.45 vs. 0.82±0.37); that of SW1990 overexpression group was higher than that of SW1990 blank vector control group (1.34±0.65 vs. 0.51±0.22), and the differences were statistically significant ( t=1.414, 1.378, 1.319 and 1.934, all P<0.05). The cell proliferation of ASPC1 knockdown group was slower than that of ASPC1 blank vector control group, and the proliferation peak at 80 h was lower than that of blank vector control group (1.02±0.77 vs. 4.31±2.45); the cell proliferation of BXPC3 knockdown group was slower than that of BXPC3 blank vector control group, and the proliferation peak at 80 h was lower than that of blank vector control group (0.91±0.24 vs. 2.84±0.53); the proliferation of pancreatic cancer cells in SW1990 overexpression group was faster than that of SW1990 blank vector control group, and the proliferation peak at 80 h was higher than that of blank vector control group (3.10±0.67 vs. 1.04±0.17); the proliferation of pancreatic cancer cells in CFPAC1 overexpression group was faster than that that of CFPAC1 blank vector control group, and the proliferation peak at 80 h was higher than that of blank vector control group (5.45±1.13 vs. 1.01±0.29), and the differences were statistically significant ( t=1.427, 1.316, 1.292 and 1.501, all P<0.05). In the test of migration ability, the number of cells passed through the Transwell chamber of ASPC1 knockdown group was less than that of ASPC1 blank vector control group (34.08±17.62 vs. 118.76±5.31); that of BXPC3 knockdown group was less than that of BXPC3 blank vector control group (18.62±9.64 vs. 57.90±12.67); that of SW1990 overexpression group was more than that of SW1990 blank vector control group (134.84±24.65 vs. 37.82±6.73); that of CFPAC1 overexpression group was more than that of CFPAC1 blank vector control group (65.79±27.46 vs. 11.68±5.13), and the differences were statistically significant ( t=1.475, 1.322, 1.437 and 1.219, all P<0.05). In the test of invasion ability, the number of cells passed through the Transwell chamber of ASPC1 knockdown group was less than that of ASPC1 blank vector control group (9.79±5.75 vs. 45.76±12.71); that of BXPC3 knockdown group was less than that of BXPC3 blank vector control group (23.46±11.13 vs. 84.92±17.65); that of SW1990 overexpression group was more than that of SW1990 blank vector control group (156.42±34.50 vs. 42.13±22.17); that of CFPAC1 overexpression group was more than that of CFPAC1 blank vector control group (112.64±47.82 vs. 39.09±17.23), and the differences were statistically significant ( t=1.324, 1.635, 1.423 and 1.119, all P<0.05). The number of colony formation of the ASPC1 knockdown group was less than that of ASPC1 blank vector control group (13.15±6.42 vs. 86.79±35.17); that of BXPC3 knockdown group was less than that of BXPC3 blank vector control group (14.93±9.30 vs. 52.93±15.76); that of SW1990 overexpression group was more than that of SW1990 blank vector control group (129.10±57.31 vs. 62.42±37.43); that of CFPAC1 overexpression group was more than that of CFPAC1 blank vector control group (157.98±66.45 vs. 74.35±34.69), and the differences were statistically significant ( t=1.148, 1.290, 1.274 and 1.462, all P<0.05). The MYST2 score of pancreatic cancer tissues was higher than that of adjacent paracancerous pancreatic tissues (3.04±2.23 vs. 1.32 ± 0.70), and the difference was statistically significant ( t=3.479, P<0.05). When the total immunohistochemistry score of MYST2 was 3 point, the area under the curve was the largest (0.888, 95% confidence interval 0.827 to 0.948), and the Youden index was 0.56. Conclusion:MYST2 is associated with the proliferation, invasion and migration of pancreatic cancer cells, and promotes the development of pancreatic cancer.
