Sato Naoko, Motoi Fuyuhiko, Tajiki Hana, Kawaguchi Kei, Ohtsuka Hideo, Takadate Tatuyuki, Nakagawa Kei, Takagi Kiyoshi, Suzuki Takashi, Katayose Yu, Fukudo Shin, Unno Michiaki
School of Nursing, Fukushima Medical University, Fukushima, Japan.
Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Gastro Hep Adv. 2022 Sep 16;2(1):147-155. doi: 10.1016/j.gastha.2022.09.003. eCollection 2023.
Corticotropin-releasing hormone (CRH) is a major regulator of the stress response to internal and external factors. CRH and its receptors (CRHR1 and CRHR2) are expressed in the central nervous system and some cancer cells, suggesting the importance of CRH signaling in pancreatic cancers. However, the clinicopathological significance of CRH remains unknown because the immunolocalization of CRH, CRHR1, and CRHR2 has not been examined in pancreatic carcinoma tissues. We clarified the correlation of the expression of CRH and its receptors with overall survival in pancreatic cancer.
This study evaluated 96 patients with pancreatic cancer who underwent microscopic complete resection (R0) but not neoadjuvant chemotherapy from 1988 to 2007 at Tohoku University Hospital, Japan. CRH, CRHR1, and CRHR2 immunoreactivity were detected in the pancreatic carcinoma cells. Overall survival curves were generated according to the Kaplan-Meier method.
CRHR1 immunoreactivity was significantly associated with an increased risk of poorer prognosis in all patients ( = .038) and the adjuvant therapy group ( = .022). Overall survival was worse in the CRHR1-positive group than in the CRHR1-negative group among the 62 patients treated with gemcitabine hydrochloride ( = .046) and the 22 patients treated with other drugs ( = .047). CRHR1 expression was correlated with survival in univariate analysis but not in multivariate analysis.
This study is the first to immunolocalize CRH, CRHR1, and CRHR2 in pancreatic carcinoma tissues and to examine the biological prognosis. This study revealed that survival in patients with pancreatic cancer was significantly associated with expression of CRHR1 by assessing biological progression according to CRH and the expression of its receptors. However, CRHR1 expression was correlated with survival in univariate analysis but not in multivariate analysis.
促肾上腺皮质激素释放激素（CRH）是对内部和外部因素应激反应的主要调节因子。CRH及其受体（CRHR1和CRHR2）在中枢神经系统和一些癌细胞中表达，提示CRH信号在胰腺癌中的重要性。然而，由于尚未在胰腺癌组织中检测CRH、CRHR1和CRHR2的免疫定位，CRH的临床病理意义仍不清楚。我们阐明了CRH及其受体的表达与胰腺癌总生存期的相关性。
本研究评估了1988年至2007年在日本东北大学医院接受显微镜下根治性切除（R0）但未接受新辅助化疗的96例胰腺癌患者。在胰腺癌细胞中检测CRH、CRHR1和CRHR2的免疫反应性。根据Kaplan-Meier方法生成总生存曲线。
CRHR1免疫反应性在所有患者（P = 0.038）和辅助治疗组（P = 0.022）中均与预后较差风险增加显著相关。在62例接受盐酸吉西他滨治疗的患者（P = 0.046）和22例接受其他药物治疗的患者（P = 0.047）中，CRHR1阳性组的总生存期比CRHR1阴性组更差。CRHR1表达在单因素分析中与生存相关，但在多因素分析中不相关。
本研究首次在胰腺癌组织中对CRH、CRHR1和CRHR2进行免疫定位并检查生物学预后。本研究表明，通过根据CRH及其受体的表达评估生物学进展，胰腺癌患者的生存与CRHR1的表达显著相关。然而，CRHR1表达在单因素分析中与生存相关，但在多因素分析中不相关。
