Wojakowska Anna, Marczak Lukasz, Zeman Marcin, Chekan Mykola, Zembala-Nożyńska Ewa, Polanski Krzysztof, Strugała Aleksander, Widlak Piotr, Pietrowska Monika
Laboratory of Mass Spectrometry, Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznan, Poland.
The Oncologic and Reconstructive Surgery Clinic, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland.
Front Oncol. 2024 Feb 12;14:1323961. doi: 10.3389/fonc.2024.1323961. eCollection 2024.
Neoadjuvant radiotherapy (neo-RT) is widely used in locally advanced rectal cancer (LARC) as a component of radical treatment. Despite the advantages of neo-RT, which typically improves outcomes in LARC patients, the lack of reliable biomarkers that predict response and monitor the efficacy of therapy, can result in the application of unnecessary aggressive therapy affecting patients' quality of life. Hence, the search for molecular biomarkers for assessing the radio responsiveness of this cancer represents a relevant issue.
Here, we combined proteomic and metabolomic approaches to identify molecular signatures, which could discriminate LARC tumors with good and poor responses to neo-RT.
The integration of data on differentially accumulated proteins and metabolites made it possible to identify disrupted metabolic pathways and signaling processes connected with response to irradiation, including ketone bodies synthesis and degradation, purine metabolism, energy metabolism, degradation of fatty acid, amino acid metabolism, and focal adhesion. Moreover, we proposed multi-component panels of proteins and metabolites which could serve as a solid base to develop biomarkers for monitoring and predicting the efficacy of preoperative RT in rectal cancer patients.
We proved that an integrated multi-omic approach presents a valid look at the analysis of the global response to cancer treatment from the perspective of metabolomic reprogramming.
新辅助放疗（neo-RT）作为根治性治疗的一部分，广泛应用于局部晚期直肠癌（LARC）。尽管新辅助放疗具有优势，通常能改善LARC患者的预后，但缺乏可靠的生物标志物来预测反应和监测治疗效果，可能导致应用不必要的激进治疗，影响患者生活质量。因此，寻找评估该癌症放射反应性的分子生物标志物是一个相关问题。
在此，我们结合蛋白质组学和代谢组学方法来识别分子特征，这些特征可以区分对新辅助放疗反应良好和反应不佳的LARC肿瘤。
整合差异积累的蛋白质和代谢物数据，使得识别与辐射反应相关的代谢途径和信号传导过程的破坏成为可能，包括酮体合成与降解、嘌呤代谢、能量代谢、脂肪酸降解、氨基酸代谢和粘着斑。此外，我们提出了蛋白质和代谢物的多组分组合，它们可以作为开发生物标志物的坚实基础，用于监测和预测直肠癌患者术前放疗的疗效。
我们证明，从代谢组重编程的角度来看，综合多组学方法为分析癌症治疗的整体反应提供了一个有效的视角。
