Romanowicz Adrianna, Łukaszewicz-Zając Marta, Mroczko Barbara
Department of Biochemical Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland.
Department of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland.
Int J Mol Sci. 2025 Sep 7;26(17):8715. doi: 10.3390/ijms26178715.
Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide, mainly due to late diagnosis and high metastatic potential. Effective management requires accurate diagnostic, prognostic, and therapeutic strategies, with growing focus on molecular biomarkers. Chemokines, which are small, secreted proteins regulating immune cell migration and tissue homeostasis, shape the tumor microenvironment by promoting tumor growth, angiogenesis, immune evasion, and metastasis. In CRC, the expression of altered chemokine-receptor profiles correlates with progression and clinical outcomes. Chemokines are classified by the presence or absence of the ELR motif, which differentiates CXC subgroups. Selection focused on those consistently altered in CRC tissues or serum and involved in key oncogenic processes. CXCL1 and its receptor CXCR2 are overexpressed and linked to tumor progression, highlighting their diagnostic and therapeutic potential. CXCL8 is elevated in tissues and serum, correlating with metastasis and poor survival. The CXCL12/CXCR4/CXCR7 axis drives metastasis. CXCL13 promotes immune evasion via CXCR5, while CXCL14 is downregulated, suggesting a protective role. Moreover, CXCL16 associates with worse outcomes, whereas CXCR6 may enhance immunotherapy response. Overall, chemokines and receptors are promising blood biomarkers and therapeutic targets in CRC. Further validation is needed using large prospective studies, standardized assays, and multi-marker approaches to establish their potential as non-invasive CRC biomarkers.
结直肠癌(CRC)是全球癌症相关发病和死亡的主要原因之一,主要归因于诊断延迟和高转移潜能。有效的管理需要准确的诊断、预后和治疗策略,且越来越关注分子生物标志物。趋化因子是一类调节免疫细胞迁移和组织稳态的小型分泌蛋白,通过促进肿瘤生长、血管生成、免疫逃逸和转移来塑造肿瘤微环境。在结直肠癌中,趋化因子受体谱的改变与疾病进展和临床结局相关。趋化因子根据是否存在ELR基序进行分类,该基序可区分CXC亚组。选择重点关注那些在结直肠癌组织或血清中持续改变且参与关键致癌过程的趋化因子。CXCL1及其受体CXCR2过表达并与肿瘤进展相关,凸显了它们的诊断和治疗潜力。CXCL8在组织和血清中升高,与转移和不良生存相关。CXCL12/CXCR4/CXCR7轴驱动转移。CXCL13通过CXCR5促进免疫逃逸,而CXCL14表达下调,提示其具有保护作用。此外,CXCL16与更差的预后相关,而CXCR6可能增强免疫治疗反应。总体而言,趋化因子及其受体有望成为结直肠癌有前景的血液生物标志物和治疗靶点。需要通过大型前瞻性研究、标准化检测和多标志物方法进行进一步验证,以确立它们作为结直肠癌非侵入性生物标志物的潜力。