Identification of Early Events in Serrated Pathway Colorectal Tumorigenesis by Using Digital Spatial Profiling

Area of Science:

• Molecular oncology
• Gastroenterology
• Cancer research

Background:

• The colorectal serrated pathway, including sessile serrated lesions (SSL) and traditional serrated adenomas (TSA), is initiated by BRAF or KRAS mutations.
• Progression to invasive carcinoma involves further genetic and epigenetic alterations.

Purpose of the Study:

• To investigate transcriptional changes in early colorectal serrated lesions using digital spatial profiling.
• To confirm gene expression via immunohistochemistry (IHC) and elucidate the role of CEACAM6 in colorectal cancer (CRC) tumorigenesis.

Main Methods:

• Digital spatial profiling to identify transcriptional signatures in SSL and TSA.
• Immunohistochemical (IHC) staining to validate gene expression.
• CRC cell line models to assess CEACAM6 function in proliferation, migration, and invasion.

Main Results:

• Ten genes were upregulated in SSL and TSA; seven were upregulated in both.
• CEACAM6, LCN2, KRT19, and lysozyme were confirmed as overexpressed in SSL and TSA.
• CEACAM6 acts as an early event in the serrated pathway and promotes CRC cell tumorigenesis.

Conclusions:

• Early-stage tumorigenesis in the serrated pathway shows uniform transcriptional changes.
• Identifying these early molecular events is crucial for understanding tumor initiation mechanisms.