Exploring Site-Specific N 6 -Methyladenosine Modifications as New Cancer Biomarkers via SERS-Based Single-Cell Assay and Histopathological Imaging

作者：Sijia Sun, Dan Xie, Wenyan Guan, Qi Li, Jian He, Ying Li, Jingran Chen, Song Gao, Zhen Liu · 发表于：Analytical Chemistry · 年份：2025 · DOI：10.1021/acs.analchem.5c01864 · 被引用次数：5 · 研究领域：RNA modifications and cancer、RNA and protein synthesis mechanisms、Advanced biosensing and bioanalysis techniques

Identifying new cancer biomarkers is crucial for cancer diagnosis. The modification sites of N 6 -methyladenosine (m 6 A) significantly influence its regulatory effects on RNA expression and cellular function, suggesting that site-specific m 6 A modifications may serve as more valuable cancer biomarkers than global m 6 A or m 6 A signatures of individual RNA transcripts. However, this potential has largely remained unexplored. In this study, we developed a comprehensive strategy for assessing the clinical value of site-specific m 6 A modifications via combining the high specificity of an m 6 A-sensitive DNAzyme with the ultrasensitivity of surface-enhanced Raman scattering (SERS) detection and imaging. Using this strategy, we first identified three m 6 A sites that could serve as biomarkers for pancreatic cancer diagnosis and breast cancer subtyping through single-cell and tissue extract assays. Further, we spatially mapped m 6 A modifications on clinical formalin-fixed, paraffin-embedded (FFPE) tissue sections. The SERS imaging of the three m 6 A sites on tissue sections enabled not only the differentiation of pancreatic ductal adenocarcinoma (PDAC) and breast cancer from normal tissues but also the differentiation between triple-negative breast cancer (TNBC) and luminal A breast cancer (LABC). Our strategy exhibits multiple significant merits, including high sensitivity and specificity, preservation of cellular context, versatility across sample types, spatial mapping capab...