Differentially Expressed Somatostatin (SST) and Its Receptors (SST1-5) in Sporadic Colorectal Cancer and Normal Colorectal Mucosa

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2024 Nov 9

PMID 39518025

Authors

Agnieszka Geltz

Agnieszka Seraszek-Jaros

Malgorzata Andrzejewska

Paulina Pietras

Marta Lesniczak-Staszak

Witold Szaflarski

Jacek Szmeja

Aldona Kasprzak

Affiliations

Soon will be listed here.

Abstract

Background/objectives: Colorectal cancer (CRC) is one of the most common human malignancies worldwide. The somatotropin-releasing inhibitory factor/somatostatin (SRIF/SST) acts through activation of five membrane receptors (SSTRs, SST1-5). The diagnostic and prognostic role of these peptides in sporadic CRC remains unclear. This study aimed to determine the role of tissue expression of SST and all SSTRs in the pathogenesis, diagnosis, and prognosis of sporadic CRC.

Methods: The expression of SST and all SSTRs was assessed in the tissues of CRC patients, control colorectal mucosa and lymph node metastasis from the same patients using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC).

Results: Decreased SST (mRNA and peptide) and higher SST2 and SST5 (mRNA and peptide) expression in CRC vs. control was noted. A negative correlation between SST mRNA expression and patient's age in CRC and control groups were observed. IHC study confirmed the coexpression of SSTRs in all tissue groups and significant dependence on the cellular localization. Immunoexpression of SST2 and SST3 showed the most correlations with clinicopathological data in CRC patients. Interestingly, only control tissue showed differences in SST1-5 expression depending on the colon segment.

Conclusions: Reduced SST expression in CRC indicates a weakening in its antitumor effect in this cancer in vivo. Overexpression of SST2 and SST5 in CRC suggests that these receptors play an important role in the pathogenesis of this cancer. Analysis of SST1-5 tissue expression allows for differentiation between the mucinous and nonmucinous CRC subtypes. The coexpression of all SST1-5 and overexpression of not only SST2 and SST5 in CRC may have applications for future therapy based on the SRIF system in sporadic CRC.

References

Petrelli F, Tomasello G, Borgonovo K, Ghidini M, Turati L, Dallera P . Prognostic Survival Associated With Left-Sided vs Right-Sided Colon Cancer: A Systematic Review and Meta-analysis. JAMA Oncol. 2016; 3(2):211-219. DOI: 10.1001/jamaoncol.2016.4227. View

Raggi C, Calabro A, Renzi D, Briganti V, Cianchi F, Messerini L . Quantitative evaluation of somatostatin receptor subtype 2 expression in sporadic colorectal tumor and in the corresponding normal mucosa. Clin Cancer Res. 2002; 8(2):419-27. View

Kasprzak A . Somatostatin and Its Receptor System in Colorectal Cancer. Biomedicines. 2021; 9(11). PMC: 8615525. DOI: 10.3390/biomedicines9111743. View

Barbieri F, Bajetto A, Pattarozzi A, Gatti M, Wurth R, Thellung S . Peptide receptor targeting in cancer: the somatostatin paradigm. Int J Pept. 2013; 2013:926295. PMC: 3582104. DOI: 10.1155/2013/926295. View

Hu Y, Ye Z, Wang F, Qin Y, Xu X, Yu X . Role of Somatostatin Receptor in Pancreatic Neuroendocrine Tumor Development, Diagnosis, and Therapy. Front Endocrinol (Lausanne). 2021; 12:679000. PMC: 8170475. DOI: 10.3389/fendo.2021.679000. View

Gurgul E, Kasprzak A, Blaszczyk A, Biczysko M, Surdyk-Zasada J, Seraszek-Jaros A . Ghrelin and obestatin in thyroid gland - immunohistochemical expression in nodular goiter, papillary and medullary cancer. Folia Histochem Cytobiol. 2015; 53(1):19-25. DOI: 10.5603/FHC.a2015.0004. View

Aran D, Camarda R, Odegaard J, Paik H, Oskotsky B, Krings G . Comprehensive analysis of normal adjacent to tumor transcriptomes. Nat Commun. 2017; 8(1):1077. PMC: 5651823. DOI: 10.1038/s41467-017-01027-z. View

Kim K, Kim Y, Shim H, Kim B, Kwon H . Differences in clinical features and oncologic outcomes between metastatic right and left colon cancer. J BUON. 2019; 23(7):11-18. View

Jung G, Hernandez-Illan E, Moreira L, Balaguer F, Goel A . Epigenetics of colorectal cancer: biomarker and therapeutic potential. Nat Rev Gastroenterol Hepatol. 2020; 17(2):111-130. PMC: 7228650. DOI: 10.1038/s41575-019-0230-y. View

10.

Vuaroqueaux V, Dutour A, Bourhim N, Ouafik L, Monges G, Briard N . Increased expression of the mRNA encoding the somatostatin receptor subtype five in human colorectal adenocarcinoma. J Mol Endocrinol. 2000; 24(3):397-408. DOI: 10.1677/jme.0.0240397. View

11.

Swatek J, CHIBOWSKI D . Endocrine cells in colorectal carcinomas. Immunohistochemical study. Pol J Pathol. 2001; 51(3):127-36. View

12.

Kasprzak A, Siodla E, Andrzejewska M, Szmeja J, Seraszek-Jaros A, Cofta S . Differential expression of mucin 1 and mucin 2 in colorectal cancer. World J Gastroenterol. 2018; 24(36):4164-4177. PMC: 6158483. DOI: 10.3748/wjg.v24.i36.4164. View

13.

Kasprzak A, Geltz A . The State-of-the-Art Mechanisms and Antitumor Effects of Somatostatin in Colorectal Cancer: A Review. Biomedicines. 2024; 12(3). PMC: 10968376. DOI: 10.3390/biomedicines12030578. View

14.

Puppa G, Sonzogni A, Colombari R, Pelosi G . TNM staging system of colorectal carcinoma: a critical appraisal of challenging issues. Arch Pathol Lab Med. 2010; 134(6):837-52. DOI: 10.5858/134.6.837. View

15.

Seretis E, Konstantinidou A, Arnogiannakis N, Xinopoulos D, Voloudakis-Baltatzis I . Mucinous colorectal adenocarcinoma with signet-ring cells: immunohistochemical and ultrastructural study. Ultrastruct Pathol. 2010; 34(6):337-43. DOI: 10.3109/01913123.2010.500069. View

16.

La Salvia A, Espinosa-Olarte P, Del Carmen Riesco-Martinez M, Anton-Pascual B, Garcia-Carbonero R . Targeted Cancer Therapy: What's New in the Field of Neuroendocrine Neoplasms?. Cancers (Basel). 2021; 13(7). PMC: 8038369. DOI: 10.3390/cancers13071701. View

17.

Ng L, Li H, Man A, Chow A, Foo D, Lo O . High Expression of a Cancer Stemness-Related Gene, Chromobox 8 (CBX8), in Normal Tissue Adjacent to the Tumor (NAT) Is Associated with Poor Prognosis of Colorectal Cancer Patients. Cells. 2022; 11(11). PMC: 9180723. DOI: 10.3390/cells11111852. View

18.

Ohmori T, Okada K, TABEI R . Immunoreactivity to neurohormonal polypeptide in colorectal carcinomas and tumor-neighboring mucosa, and its significance. Arch Pathol Lab Med. 1996; 120(6):560-8. View

19.

Jesinghaus M, Konukiewitz B, Keller G, Kloor M, Steiger K, Reiche M . Colorectal mixed adenoneuroendocrine carcinomas and neuroendocrine carcinomas are genetically closely related to colorectal adenocarcinomas. Mod Pathol. 2017; 30(4):610-619. DOI: 10.1038/modpathol.2016.220. View

20.

Ohmori T, Asahi S, Sato C, Maki F, Masumoto A, Okada K . Bcl-2 protein expression and gut neurohormonal polypeptide/amine production in colorectal carcinomas and tumor-neighboring mucosa, which closely correlate to the occurrence of tumor. Histol Histopathol. 1999; 14(1):37-44. DOI: 10.14670/HH-14.37. View