Department of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
Department of Oncology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
Int J Mol Sci. 2023 Jan 30;24(3):2581. doi: 10.3390/ijms24032581.
The overexpression of the pH regulator carbonic anhydrase IX (CAIX) due to hypoxic/metabolic stress was reported in various tumors as an adverse prognostic feature. Our retrospective study aimed to investigate the general pattern and dynamics of CAIX expression in rectal adenocarcinoma following preoperative neoadjuvant therapy (NAT) in matched initial biopsy and surgical resection samples. A total of 40/55 (72.72%) of the post-treatment samples showed partial CAIX expression, frequently in the proximity of hypoxic tumor areas. CAIX expression showed a significant increase in post-treatment tumors (mean% 21.8 ± 24.9 SD vs. 39.4 ± 29.4 SD, < 0.0001), that was not obvious in untreated tumors (mean% 15.0 ± 21.3 SD vs. 20 ± 23.02, = 0.073). CAIXhigh phenotype was associated with mutant status and lack of pathological regression (WHO Tumor Regression Grade 4 and 5). However, the adverse effect of CAIX on overall or progression-free survival could not be statistically confirmed. In conclusion, the dynamic upregulation of CAIX expression is a general feature of rectal adenocarcinoma following neoadjuvant chemo-radiotherapy indicating therapy-induced metabolic reprogramming and cellular adaptation. A synergism of the CAIX-associated regulatory pathways and the mutant oncogenic signaling most likely contributes to therapy resistance and survival of residual cancer.
碳酸酐酶 IX（CAIX）在缺氧/代谢应激下的过表达被报道存在于各种肿瘤中，是一种不良预后特征。我们的回顾性研究旨在调查直肠腺癌在术前新辅助治疗（NAT）后在匹配的初始活检和手术切除样本中 CAIX 表达的总体模式和动态。治疗后样本中共有 40/55（72.72%）显示部分 CAIX 表达，常靠近缺氧肿瘤区域。CAIX 表达在治疗后的肿瘤中显著增加（平均%21.8 ± 24.9 SD 与 39.4 ± 29.4 SD， < 0.0001），而在未治疗的肿瘤中不明显（平均%15.0 ± 21.3 SD 与 20 ± 23.02， = 0.073）。CAIXhigh 表型与突变 状态和缺乏病理消退（WHO 肿瘤消退分级 4 和 5）相关。然而，CAIX 对总生存或无进展生存的不良影响不能被统计学证实。总之，CAIX 表达的动态上调是直肠腺癌在新辅助放化疗后的一个普遍特征，表明治疗诱导的代谢重编程和细胞适应。CAIX 相关调节途径与突变 致癌信号的协同作用可能导致治疗耐药和残留癌细胞的存活。
