醛脱氢酶1A1（ALDH1A1）表达的临床意义及其与切除的大细胞神经内分泌癌中E-钙黏蛋白和N-钙黏蛋白的关系

Clinical significance of ALDH1A1 expression and its association with E-cadherin and N-cadherin in resected large cell neuroendocrine carcinoma.

作者信息

Zhang Jinyao, Sun Xujie, Liu Li, Dong Jiyan, Deng Lei, Wang Xin, Guo Yiying, Ying Jianming, Xing Puyuan, Li Junling, Yang Lin

机构信息

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

出版信息

Transl Oncol. 2022 May;19:101379. doi: 10.1016/j.tranon.2022.101379. Epub 2022 Feb 23.

DOI:10.1016/j.tranon.2022.101379

PMID:35219092

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8881670/

Abstract

BACKGROUND

The roles of cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) in solid tumors are well established. However, the interaction between CSCs and EMT in pulmonary large cell neuroendocrine carcinoma (LCNEC) remains unknown. The aim of this study was to investigate the expression and clinical significance of a CSC marker (ALDH1A1) and its correlation with Epithelial-like phenotype marker (E-cadherin) and Mesenchymal-like phenotype marker (N-cadherin) in LCNEC patients.

METHODS

Immunohistochemistry (IHC) for ALDH1A1, E-cadherin and N-cadherin expression was conducted on tissue microarrays made from 79 resected LCNEC patient samples. ALDH1A1 protein expression was evaluated by the IHC score, and its correlations with the expression of E-cadherin, N-cadherin and clinicopathological features were determined based on IHC data. Survival analyses were also performed.

RESULTS

ALDH1A1 was positively expressed in 75.9% (60/79 cases) of LCNEC patients. No significant difference in clinicopathological variables was observed between the ALDH1A1-negative and ALDH1A1-positive groups. However, ALDH1A1 expression was positively correlated with E-cadherin (Spearman's rho = 0.229, p-value = 0.007), which represents the epithelial-like phenotype, but not with N-cadherin. Patients with expression of ALDH1A1 had significantly longer disease-free survival (DFS) and overall survival (OS) than those who were ALDH1A1 negative (median DFS: 52 vs 12 months, p = 0.028; median OS: not reached; p = 0.027). Multivariate analysis showed that ALDH1A1 was an independent favorable prognostic factor for DFS (p = 0.032, HR: 0.438, 95% CI: 0.206-0.932) and OS (p = 0.025, HR: 0.279, 95% CI: 0.091-0.852) in LCNEC patients.

CONCLUSION

This study suggests that ALDH1A1 can act as a favorable independent prognostic factor for LCNEC, which related to the epithelioid phenotype in EMT, and its internal mechanism needs further study.

摘要

背景

癌症干细胞（CSCs）和上皮-间质转化（EMT）在实体瘤中的作用已得到充分证实。然而，CSCs与EMT在肺大细胞神经内分泌癌（LCNEC）中的相互作用仍不清楚。本研究旨在探讨CSC标志物（ALDH1A1）在LCNEC患者中的表达及临床意义，及其与上皮样表型标志物（E-钙黏蛋白）和间充质样表型标志物（N-钙黏蛋白）的相关性。

方法

对79例LCNEC患者手术切除标本制作的组织芯片进行ALDH1A1、E-钙黏蛋白和N-钙黏蛋白表达的免疫组织化学（IHC）检测。通过IHC评分评估ALDH1A1蛋白表达，并根据IHC数据确定其与E-钙黏蛋白、N-钙黏蛋白表达及临床病理特征的相关性。同时进行生存分析。

结果

75.9%（60/79例）的LCNEC患者ALDH1A1呈阳性表达。ALDH1A1阴性组和阳性组在临床病理变量上无显著差异。然而，ALDH1A1表达与代表上皮样表型的E-钙黏蛋白呈正相关（Spearman相关系数=0.229，p值=0.007），与N-钙黏蛋白无相关性。ALDH1A1表达阳性的患者无病生存期（DFS）和总生存期（OS）显著长于ALDH1A1阴性患者（中位DFS：52个月对12个月，p=0.028；中位OS：未达到；p=0.027）。多因素分析显示，ALDH1A1是LCNEC患者DFS（p=0.032，HR：0.438，95%CI：0.206-0.932）和OS（p=0.025，HR：0.279，95%CI：0.091-0.852）的独立有利预后因素。