Clinicopathological and prognostic significance of SWI/SNF complex subunits in undifferentiated gastric carcinoma.
Clinicopathological and prognostic significance of SWI/SNF complex subunits in undifferentiated gastric carcinoma.
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SWI/SNF复合物亚单位在未分化胃癌中的临床病理及预后意义
DOI：
10.1186/s12957-022-02847-0
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发表时间：
2022-12-04
影响因子：
3.2
通讯作者：
Zhang, Shukun
中科院分区：
文献类型：
--
作者：
Zhang, Zhenkun;Li, Qiujing;Sun, Shanshan;Li, Zhe;Cui, Zheng Guo;Zhang, Menglan;Liu, Qian;Zhang, Yujie;Xiong, Sili;Zhang, Shukun
开关/蔗糖不可发酵（SWI/SNF）复合物是一种进化上保守的染色质重塑复合物，在许多肿瘤，特别是未分化癌中显示功能障碍。肿瘤干细胞（cancer stem cells，CSC）是一类特殊的未分化肿瘤细胞，具有干细胞样特性，在肿瘤细胞增殖、侵袭和转移中起重要作用。在未分化胃癌中，SWI/SNF复合物与临床病理特征、CSC表型和预后的关系尚不完全清楚。我们收集了21例未分化/去分化胃癌患者。接下来，我们对SWI/SNF复合物的五个亚基（ARID 1A、ARID 1B、SMARCA 2、SMARCA 4和SMARCA 1）和四种错配修复蛋白（MLH 1、PMS 2、MSH 2和MSH 6）以及其他标志物（如p53、PD-L1和癌症干细胞（CSC）标志物（SOX 2、SALL 4））进行了免疫组织化学染色。研究SWI/SNF复合物亚单位与临床病理特征的相关性，并进行预后分析。我们观察到12例（57.14%）SMARCA 2丢失，其次是ARID 1A（5例，23.81%）和SMARCA 4（3例，14.29%）。SWI/SNF复合物任一亚基缺失者14例（66.67%），其中SMARCA 2和ARID 1A共缺失3例，SMARCA 2和SMARCA 4共缺失3例。相关分析显示，CSC表型更频繁地发生在SWI/SNF复合物缺陷组（P = 0.0158）。生存分析显示，SWI/WNF复合物缺陷、未分化状态、CSC表型以及SMARCA 2和SMARCA 4缺失导致生存较差。单因素和多因素考克斯回归分析筛选出3个独立的与预后不良相关的因素：未分化状态、SWI/SNF复合物缺乏和淋巴结转移。SWI/SNF复合物缺陷更可能导致CSC表型和更差的生存率，并且是未分化/去分化胃癌的独立预后因素。在线版本包含补充材料，可通过10.1186/s12957-022-02847-0获得。
The 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. We 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. We 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. The 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. The online version contains supplementary material available at 10.1186/s12957-022-02847-0.
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影响因子：
24.5
作者：
Thompson ED;Zahurak M;Murphy A;Cornish T;Cuka N;Abdelfatah E;Yang S;Duncan M;Ahuja N;Taube JM;Anders RA;Kelly RJ
通讯作者：
Kelly RJ
影响因子：
3.3
作者：
Kim, Young-Bae;Ham, In-Hye;Lee, Dakeun
通讯作者：
Lee, Dakeun
影响因子：
5.3
作者：
Wilson, Boris G.;Helming, Katherine C.;Roberts, Charles W. M.
通讯作者：
Roberts, Charles W. M.
影响因子：
5.6
作者：
Perret, Raul;Chalabreysse, Lara;Le Loarer, Francois
通讯作者：
Le Loarer, Francois
DOI：
10.1073/pnas.1703966114
发表时间：
2017-11-14
影响因子：
11.1
作者：
Januario, Thomas;Ye, Xiaofen;Yauch, Robert L.
通讯作者：
Yauch, Robert L.