Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan.
J Clin Pathol. 2012 Aug;65(8):687-92. doi: 10.1136/jclinpath-2012-200786. Epub 2012 May 8.
Neoadjuvant chemoradiation therapy (CRT) is an increasingly used therapeutic strategy for rectal cancer. Clinically, it remains a major challenge to predict therapeutic response and patient outcome after CRT. Rsf-1 (HBXAP), a novel nuclear protein with histone chaperon function, mediates ATPase-dependent chromatin remodelling and confers tumour aggressiveness and predicts therapeutic response in certain carcinomas. However, the expression of Rsf-1 has never been reported in rectal cancer. This study examined the predictive and prognostic impacts of Rsf-1 expression in patients with rectal cancer following neoadjuvant CRT.
Rsf-1 immunoexpression was retrospectively assessed for pre-treatment biopsies of 172 rectal cancer patients without initial distant metastasis. All of them were treated with neoadjuvant CRT followed by surgery. The results were correlated with the clinicopathological features, therapeutic response, tumour regression grade and metastasis-free survival (MeFS), local recurrent-free survival and disease-specific survival.
Present in 82 cases (47.7%), high-expression of Rsf-1 was associated with advanced pre-treatment tumour status (T3, T4, p=0.020), advanced post-treatment tumour status (T3, T4, p<0.001) and inferior tumour regression grade (p=0.028). Of note, high-expression of Rsf-1 emerged as an adverse prognosticator for diseases-specific survival (p=0.0092) and significantly predicted worse MeFS (p=0.0006). Moreover, high-expression of Rsf-1 also remained prognostic independent for worse MeFS (HR 2.834; p=0.0214).
High-expression of Rsf-1 is associated with poor therapeutic response and adverse outcome in rectal cancer patients treated with neoadjuvant CRT, which confers tumour aggressiveness and therapeutic resistance through chromatin remodelling and represents a potential prognostic biomarker in rectal cancer.
新辅助放化疗（CRT）是直肠癌越来越多使用的治疗策略。临床上，预测 CRT 后的治疗反应和患者预后仍然是一个主要挑战。Rsf-1（HBXAP）是一种具有组蛋白伴侣功能的新型核蛋白，介导 ATP 依赖的染色质重塑，并赋予肿瘤侵袭性，预测某些癌的治疗反应。然而，Rsf-1 在直肠癌中的表达从未被报道过。本研究检测了 Rsf-1 在接受新辅助 CRT 的直肠癌患者中的表达对预测和预后的影响。
对 172 例无初始远处转移的直肠癌患者的新辅助 CRT 前活检进行了 Rsf-1 免疫表达的回顾性评估。所有患者均接受新辅助 CRT 联合手术治疗。结果与临床病理特征、治疗反应、肿瘤消退分级和无转移生存（MeFS）、局部无复发生存和疾病特异性生存相关。
在 82 例（47.7%）患者中，Rsf-1 高表达与术前肿瘤状态（T3、T4，p=0.020）、术后肿瘤状态（T3、T4，p<0.001）和肿瘤消退分级差（p=0.028）有关。值得注意的是，Rsf-1 高表达是疾病特异性生存的不良预后因素（p=0.0092），并显著预测 MeFS 更差（p=0.0006）。此外，Rsf-1 高表达仍然是 MeFS 预后不良的独立因素（HR 2.834；p=0.0214）。
在接受新辅助 CRT 的直肠癌患者中，Rsf-1 高表达与治疗反应差和不良预后相关，通过染色质重塑赋予肿瘤侵袭性和治疗抵抗性，是直肠癌潜在的预后生物标志物。
