对于局部晚期直肠癌患者化学放疗（CRT）的反应存在很大的变异性。鉴定CRT非响应者和确定准确的反应生物标志物是未满足的需求。反过来，脂联素可能会影响结直肠癌的发展。我们假设瘦素和脂联素的不平衡会调节直肠癌干细胞潜能的CRT反应。我们在局部晚期直肠癌患者（n=33）的长程CRT和直肠切除术前采集了预CRT的血清和组织样本。用ELISA法测定了血清中的脂联素和瘦素。在肿瘤活检中，通过qRT-PCR评估了与干细胞相关的基因的mRNA表达，并通过免疫印迹评估了转录因子STAT3。评估与临床数据的相关性和潜在CRT反应生物标志物的准确性。癌胚抗原（CEA）而不是瘦素或脂联素可以将CRT响应者与非响应者区分开来（p＜0.05）。然而，较高的瘦素和较低的脂联素血清水平与阳性的肠系膜外淋巴结和外层血管浸润有关。干细胞因子的mRNA表达与脂联素呈负相关，但与瘦素呈正相关。STAT3磷酸化表现出类似的结果。CEA水平与STAT3活化和OCT4/KLF4表达一起能够准确地鉴定直肠癌患者的CRT非响应者（AUROC 0.80；p＜0.05）。脂联素可能会影响直肠癌干细胞和患者预后。瘦素/STAT3信号传导途径为潜在的生物标志物面板提供了理性，可以识别不会受益于CRT治疗的直肠癌患者。© 2022。作者（s）独占许可给纳瓦拉大学。

Response to chemoradiotherapy (CRT) in patients with locally advanced rectal cancer is highly variable. Identification of CRT non-responders and definite accurate biomarkers of response are unmet needs. In turn, adipokines might impact on colorectal cancer development. We hypothesized that imbalance in leptin and adiponectin modulates stemness potential CRT response in rectal cancer. Pre-CRT serum and tissue samples were collected from a cohort of locally advanced rectal cancer patients (n = 33), submitted to long-course CRT and proctectomy. Adiponectin and leptin were measured by ELISA in serum. In tumour biopsies, mRNA expression of stemness-related genes was evaluated by qRT-PCR and transcription factor STAT3 by immunoblotting. Correlations with clinical data and accuracy of potential CRT response biomarkers were evaluated. Carcinoembryonic antigen (CEA) but not leptin or adiponectin distinguished CRT responders from non-responders (p < 0.05). However, higher leptin and lower adiponectin serum levels were associated with positive extramesorectal nodes and extramural vascular invasion. mRNA expression of stemness factors was inversely correlated with adiponectin but positively correlated with leptin. STAT3 phosphorylation presented similar results. CEA levels together with STAT3 activation and OCT4/KLF4 expression accurately identified rectal cancer patients, CRT non-responders (AUROC 0.80; p < 0.05). Adipokines might impact rectal cancer stemness and patient prognosis. The leptin/STAT3 signalling axis provides the rational for a potential biomarker panel that identifies rectal cancer patients who will not benefit from CRT treatment.© 2022. The Author(s) under exclusive licence to University of Navarra.