Background and Aims
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.
Methods
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.
Results
CRHR1 immunoreactivity was significantly associated with an increased risk of poorer
prognosis in all patients (P = .038) and the adjuvant therapy group (P = .022). Overall survival was worse in the CRHR1-positive group than in the CRHR1-negative
group among the 62 patients treated with gemcitabine hydrochloride (P = .046) and the 22 patients treated with other drugs (P = .047). CRHR1 expression was correlated with survival in univariate analysis but
not in multivariate analysis.
Conclusion
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.
Graphical abstract
Graphical Abstract
Keywords
Abbreviations used in this paper:
CRH (corticotropin-releasing hormone), CRHR1 (CRH receptor 1), CRHR2 (CRH receptor 2), GEM (gemcitabine hydrochloride)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: September 15, 2022
Accepted:
September 9,
2022
Received:
January 18,
2022
Footnotes
Conflict of Interest: The authors disclose no conflicts.
Funding: This work was supported by JSPS KAKENHI Grant Numbers JP23659120, 16K07140, 19K08063, and 19K22589, Japan.
Ethical Statement: The corresponding author, on behalf of all authors, jointly and severally, certifies that their institution has approved the protocol for any investigation involving humans or animals and that all experimentation was conducted in conformity with ethical and humane principles of research.
Data Transparency Statement: The data, analytic methods, and study materials used in this study will not be shared.
Writing Assistance: English language editing was provided by ThinkSCIENCE, Tokyo, Japan and was funded by JSPS KAKENHI Grant Number 19K08063.
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