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SMARCA2和SMARCA4在胃腺癌中的表达及列线图预后模型的构建

Expression of SMARCA2 and SMARCA4 in gastric adenocarcinoma and construction of a nomogram prognostic model.

作者信息

Zhang Zhenkun, Li Qiujing, Sun Shanshan, Li Zhe, Cui ZhengGuo, Liu Qian, Zhang Yujie, Xiong Sili, Zhang Shukun

机构信息

Weihai Municipal Hospital, Shandong University, Weihai, 264200, Shandong, China.

Department of Oncology, Shouguang People's Hospital, Weifang, 262700, Shandong, China.

出版信息

Int J Clin Oncol. 2023 Nov;28(11):1487-1500. doi: 10.1007/s10147-023-02403-0. Epub 2023 Aug 27.

Abstract

BACKGROUND

Aberrant expression of SWI/SNF complex subunits is closely associated with tumorigenesis. The clinicopathological and prognostic significance of altered SMARCA2 and SMARCA4 subunits has not been well evaluated in gastric adenocarcinoma.

METHODS

We collected 1271 postoperative cases of gastric adenocarcinoma and then constructed tissue microarrays (TMA), from which we obtained the immunohistochemistry expression of SMARCA2 and SMARCA4. Next, we screened the variables related to the loss of SMARCA2 and SMARCA4 by univariate correlation analysis and multivariate logistic regression analysis. Then, we identified the variables related to prognosis by univariate and multivariate Cox regression analysis. Finally, we constructed a nomogram prognostic model and evaluated it.

RESULTS

The loss of SMARCA2 and SMARCA4 occurred in 236 (18.57%) and 86 (6.77%) cases, respectively, including 26 cases of co-loss. After multivariate logistic regression, variables independently associated with SMARCA2 loss were T stage, differentiation status, WHO histological classification, and EBER. Variables independently associated with SMARCA4 loss were differentiation status, WHO histological classification, PD-L1, and MMR. Survival analysis revealed that the SMARCA2 and SMARCA4 lost groups showed worse survival than the corresponding present groups (P = 0.032 and P = 0.0048, respectively). Univariate and multivariate Cox analyses identified independent prognostic factors, including age, T stage, N stage, M stage, SMARCA2, and chemotherapy.

CONCLUSION

The loss of SMARCA2 and SMARCA4 correlated with poor differentiation, leading to a worse prognosis. SMARCA2, as an independent prognostic factor, combined with other clinicopathological variables, established a novel nomogram prognostic model, which outperformed the AJCC TNM model.

摘要

背景

SWI/SNF复合物亚基的异常表达与肿瘤发生密切相关。SMARCA2和SMARCA4亚基改变在胃腺癌中的临床病理及预后意义尚未得到充分评估。

方法

我们收集了1271例胃腺癌术后病例,构建组织芯片(TMA),从中获得SMARCA2和SMARCA4的免疫组化表达。接下来,通过单因素相关性分析和多因素逻辑回归分析筛选与SMARCA2和SMARCA4缺失相关的变量。然后,通过单因素和多因素Cox回归分析确定与预后相关的变量。最后,构建列线图预后模型并进行评估。

结果

SMARCA2和SMARCA4缺失分别发生在236例(18.57%)和86例(6.77%)病例中,包括26例共缺失。多因素逻辑回归后,与SMARCA2缺失独立相关的变量为T分期、分化状态、WHO组织学分类和EBER。与SMARCA4缺失独立相关的变量为分化状态、WHO组织学分类、PD-L1和MMR。生存分析显示,SMARCA2和SMARCA4缺失组的生存率低于相应的存在组(分别为P = 0.032和P = 0.0048)。单因素和多因素Cox分析确定了独立的预后因素,包括年龄、T分期、N分期、M分期、SMARCA2和化疗。

结论

SMARCA2和SMARCA4缺失与低分化相关,导致预后较差。SMARCA2作为独立的预后因素,与其他临床病理变量相结合,建立了一种新型列线图预后模型,其表现优于AJCC TNM模型。

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