Su Min-Cheng, Hsu Ching-Hsiang, Chen Ko-Chen, Lin Jun-Ru, Li Huei-Ying, Fang Yi-Ting, Huang Ruby Yun-Ju, Jeng Yung-Ming
Department of Pathology, Min-Sheng General Hospital, Taoyuan, Taiwan.
Graduate Institute of Pathology, National Taiwan University, Taipei, Taiwan.
Pathobiology. 2024;91(6):393-410. doi: 10.1159/000539612. Epub 2024 Jun 5.
The colorectal serrated pathway involves precursor lesions known as sessile serrated lesions (SSL) and traditional serrated adenomas (TSA). Mutations in BRAF or KRAS are crucial early events in this pathway. Additional genetic and epigenetic changes contribute to the progression of these lesions into high-grade lesions and, eventually, invasive carcinoma.
We employed digital spatial profiling to investigate the transcriptional changes associated with SSL and TSA. The genes identified are confirmed by immunohistochemical (IHC) staining. Colorectal cancer (CRC) cell lines with CEACAM6 overexpression and knockdown were established to study the roles of CEACAM6 on tumorigenesis of CRC.
Ten genes were upregulated in SSL and TSA, and seven were upregulated in both types of lesions. IHC staining confirmed overexpression of CEACAM6, LCN2, KRT19, and lysozyme in SSL and TSA. CEACAM6 expression is an early event in the serrated pathway but a late event in the conventional pathway. Using cell line models, we confirmed that CEACAM6 promotes CRC cells' proliferation, migration, and invasion abilities.
These results highlight that the transcriptional changes in the early stages of tumorigenesis exhibit relative uniformity. Identifying these early events may hold significant promise in elucidating the mechanisms behind tumor initiation.
结直肠锯齿状途径涉及称为无蒂锯齿状病变（SSL）和传统锯齿状腺瘤（TSA）的前体病变。BRAF或KRAS突变是该途径中的关键早期事件。额外的基因和表观遗传变化有助于这些病变进展为高级别病变，并最终发展为浸润性癌。
我们采用数字空间分析来研究与SSL和TSA相关的转录变化。通过免疫组织化学（IHC）染色确认所鉴定的基因。建立了CEACAM6过表达和敲低的结直肠癌（CRC）细胞系，以研究CEACAM6在CRC肿瘤发生中的作用。
10个基因在SSL和TSA中上调，7个基因在两种类型的病变中均上调。IHC染色证实CEACAM6、LCN2、KRT19和溶菌酶在SSL和TSA中过表达。CEACAM6表达是锯齿状途径中的早期事件，但在传统途径中是晚期事件。使用细胞系模型，我们证实CEACAM6促进CRC细胞的增殖、迁移和侵袭能力。
这些结果突出表明肿瘤发生早期阶段的转录变化表现出相对一致性。识别这些早期事件可能在阐明肿瘤起始背后的机制方面具有重大前景。
