Clinicopathological and prognostic significance of SWI/SNF complex subunits in undifferentiated gastric carcinoma

World Journal of Surgical Oncology

Research

Zheng Guo Cui¹  Shanshan Sun²  Menglan Zhang³  Qian Liu⁴  Shukun Zhang⁴  Qiujing Li⁴  Yujie Zhang⁴  Sili Xiong⁵  Zhe Li⁵  Zhenkun Zhang⁶ 

[1] Department of Environmental Health, University of Fukui School of Medical Science, 23-3 Matsuoka Shimoaizuki, 910-1193, Eiheiji, Fukui, Japan;Department of Oncology, Weihai Municipal Hospital, Shandong University, 264200, Weihai, Shandong, China;Department of Pathology, Qinghai Provincial People’s Hospital, 810000, Xining, Qinghai, China;Department of Pathology, Weihai Municipal Hospital, Shandong University, 264200, Weihai, Shandong, China;Weifang Medical College, 261053, Weifang, Shandong, China;Weihai Municipal Hospital, Shandong University, 264200, Weihai, Shandong, China;Department of Oncology, Shouguang People’s Hospital, 262700, Weifang, Shandong, China;

关键词: SWI/SNF;    SMARCA2;    SMARCA4;    Undifferentiated;    Gastric carcinoma;   

DOI  :  10.1186/s12957-022-02847-0

 received in 2022-05-21, accepted in 2022-11-20,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundThe switch/sucrose nonfermentable (SWI/SNF) complex is an evolutionarily conserved chromatin remodeling complex that displays dysfunction in many tumors, especially undifferentiated carcinoma. Cancer stem cells (CSC), a special type of undifferentiated cancer cells with stem cell-like properties, play an essential role in tumor cell proliferation, invasion, and metastasis. In undifferentiated gastric carcinomas, the association of SWI/SNF complexes with clinicopathological features, CSC phenotype, and the prognosis is not fully understood.MethodsWe collected a cohort of 21 patients with undifferentiated/dedifferentiated gastric carcinoma. We next performed immunohistochemistry staining for the five subunits of the SWI/SNF complex (ARID1A, ARID1B, SMARCA2, SMARCA4, and SMARCB1), and four mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6), as well as other markers such as p53, PD-L1, and cancer stem cell (CSC) markers (SOX2, SALL4). Then, we investigated the correlation of SWI/SNF complex subunits with clinicopathological characters and performed prognostic analysis.ResultsWe observed SMARCA2 loss in 12 cases (57.14%), followed by ARID1A (5 cases, 23.81%) and SMARCA4 (3 cases, 14.29%). Fourteen cases (66.67%) lost any one of the SWI/SNF complex subunits, including 3 cases with SMARCA2 and ARID1A co-loss, and 3 cases with SMARCA2 and SMARCA4 co-loss. Correlation analysis revealed that the CSC phenotype occurred more frequently in the SWI/SNF complex deficient group (P = 0.0158). Survival analysis revealed that SWI/WNF complex deficiency, undifferentiated status, CSC phenotype, and the loss of SMARCA2 and SMARCA4 resulted in worse survival. Univariate and multivariate Cox regression analyses screened out three independent factors associated with worse prognosis: undifferentiated status, SWI/SNF complex deficiency, and lymph node metastasis.ConclusionsThe SWI/SNF complex deficiency was more likely to result in a CSC phenotype and worse survival and was an independent prognostic factor in undifferentiated/dedifferentiated gastric carcinoma.

【 授权许可】

CC BY   
© The Author(s) 2022

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