Integrin-linked kinase pathway in heterogeneous pulmonary sarcomatoid carcinoma.
Integrin-linked kinase pathway in heterogeneous pulmonary sarcomatoid carcinoma.
复制标题
异质性肺肉瘤样癌中的整合素连接激酶通路。
DOI：
10.3892/ol.2021.12582
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发表时间：
2021
期刊：
影响因子：
2.9
通讯作者：
K. Nishio
中科院分区：
文献类型：
--
作者：
S. Shimizu;K. Sakai;T. Chikugo;T. Satou;Naoki Shiraishi;T. Mitsudomi;K. Nishio
肺肉瘤样癌（PSC）被归类为低分化，而含有肉瘤或肉瘤样分化成分的非小细胞肺癌是罕见的。PSC潜在的致癌机制尚不清楚。本研究基于PSC涉及上皮-间质转化（EMT）过程的假设，探讨了PSC的潜在致癌机制。使用靶向深度测序、全转录组分析和数字空间分析（DSP）对PSC（包括癌肉瘤、多形性癌和上皮癌标本）进行突变分析。PSC表现出独特的突变谱，具有TP 53、SYNE 1和APC突变。因此，基因表达谱的聚类允许PSC与上皮癌区分开。PSC中纤连蛋白基因表达的增加是差异谱的重要贡献者。通路分析揭示了PSC中整合素连接激酶（ILK）信号通路的活性增强。使用标记蛋白的56种抗体的DSP分析证实了PSC中纤连蛋白的显著更高表达。在肉瘤成分中观察到纤维连接蛋白表达的瘤内异质性。结论：ILK信号介导的上皮-间质转化过程可能与PSC的癌变机制有关。由ILK信号传导介导的纤连蛋白的过表达似乎在PSC转化过程中涉及的EMT中起作用。
Pulmonary sarcomatoid carcinoma (PSC) is classified as poorly differentiated, and non-small cell lung carcinomas that contained a component of sarcoma or sarcoma-like differentiation are rare. The underlying carcinogenetic mechanism governing PSC remains unclear. The current study investigated the underlying carcinogenetic mechanism of PSC based on the hypothesis that it involves the epithelial-mesenchymal transition (EMT) process. Mutation analysis of PSCs, including carcinosarcoma, pleomorphic carcinoma and epithelial carcinoma specimens, was performed using targeted deep sequencing, whole transcriptome analysis and digital spatial profiling (DSP). PSCs exhibit a distinct mutation profile, with TP53, SYNE1 and APC mutations. Therefore, clustering of the gene expression profiles allowed the PSCs to be distinguished from the epithelial carcinomas. Increased gene expression of fibronectin in PSC was an important contributor to differential profiles. Pathway analysis revealed enhanced activity of the integrin-linked kinase (ILK) signaling pathway in the PSCs. DSP analysis using 56 antibodies of marker proteins confirmed significantly higher expression of fibronectin in PSCs. Intratumor heterogeneity of fibronectin expression was observed in sarcoma components. In conclusion, epithelial-mesenchymal transition process mediated by ILK signaling may be associated with carcinogenetic mechanisms of PSC. Overexpression of fibronectin mediated by ILK signaling appears to serve a role in the EMT involved in the PSC transformation process.