Boka Harrison J, Engel Rebekah M, Georges Christine, McMurrick Paul J, Abud Helen E
Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, 3800, Australia.
Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
Mol Cancer. 2025 May 2;24(1):130. doi: 10.1186/s12943-025-02327-5.
Colorectal cancer (CRC) is stratified by heterogeneity between disease sites, with proximal right-sided CRC (RCRC) multifactorial in its distinction from distal left-sided CRC (LCRC). Notably, right-sided tumors are associated with aggressive disease characteristics which culminate in poor clinical outcomes for these patients. While factors such as mutational profile and patterns of metastasis have been suggested to contribute to differences in therapy response, the exact mechanisms through which RCRC resists effective treatment have yet to be elucidated. In response, recent analyzes, including those utilizing whole genome sequencing, transcriptional profiling, and single-cell analyses, have demonstrated that key molecular differences exist between disease sites, with differentially expressed genes spanning a diverse range of cellular functions. Here, we review and contextualize the most recent data on molecular biomarkers found to exhibit discordance between RCRC and LCRC, and highlight candidates for further investigation, including those which present promise for future clinical application. Given the present disparity in survival outcomes for RCRC patients, we expect the prognostic biomarkers presented in our review to be useful in establishing future directions for the side-specific treatment of CRC.
结直肠癌（CRC）根据疾病部位之间的异质性进行分层，近端右侧结直肠癌（RCRC）与远端左侧结直肠癌（LCRC）的区别是多因素的。值得注意的是，右侧肿瘤与侵袭性疾病特征相关，这最终导致这些患者的临床预后较差。虽然有人提出突变谱和转移模式等因素导致治疗反应存在差异，但RCRC抵抗有效治疗的确切机制尚未阐明。作为回应，最近的分析，包括那些利用全基因组测序、转录谱分析和单细胞分析的研究，已经证明疾病部位之间存在关键的分子差异，差异表达基因涵盖了多种细胞功能。在这里，我们回顾并梳理了关于分子生物标志物的最新数据，这些数据显示RCRC和LCRC之间存在不一致，并强调了有待进一步研究的候选标志物，包括那些有望用于未来临床应用的标志物。鉴于目前RCRC患者生存结果的差异，我们预计我们综述中提出的预后生物标志物将有助于为CRC的侧别特异性治疗确立未来方向。
