Background The aim of this study was to determine the regional heterogeneity and clinicopathological significance of microRNA-21 (miR-21) in advanced colorectal cancer (CRC) patients with distant metastasis.
Methods miR-21 expression was investigated by using locked nucleic acid– fluorescence in situ hybridization in the center and periphery of the primary cancer and in distant metastasis from 170 patients with advanced CRC. In addition, α-smooth muscle actin and desmin were evaluated to identify cancer-associated fibroblasts (CAFs) by using immunohistochemistry.
Results The miR-21 signal was observed in the cancer stroma. The expression of miR-21 (a score of 1–4) in the center and periphery of the primary cancer and in distant metastasis was observed in specimens from 133 (78.2%), 105 (61.8%), and 91 (53.5%) patients, respectively. miR-21 expression was heterogeneous in advanced CRC. Discordance between miR-21 expression in the center of the primary cancer and either the periphery of the primary cancer or distant metastasis was 31.7% or 44.7%, respectively. miR-21 stromal expression in the periphery of the primary cancer was significantly associated with a better prognosis (p=.004). miR-21 expression was significantly associated with CAFs in the center of the primary cancer (p=.001) and distant metastases (p=.041).
Conclusions miR-21 expression is observed in cancer stroma related to the CAF quantity and frequently presents regional heterogeneity in CRC. Our findings indicate that the role of miR-21 in predicting prognosis may be controversial but provide a new perspective of miR-21 level measurement in cancer specimens.
Citations
Citations to this article as recorded by
Expression of Selected miRNAs in Normal and Cancer-Associated Fibroblasts and in BxPc3 and MIA PaCa-2 Cell Lines of Pancreatic Ductal Adenocarcinoma Václav Mandys, Alexey Popov, Robert Gürlich, Jan Havránek, Lucie Pfeiferová, Michal Kolář, Jana Vránová, Karel Smetana, Lukáš Lacina, Pavol Szabo International Journal of Molecular Sciences.2023; 24(4): 3617. CrossRef
MicroRNAs and colorectal cancer: clinical potential and regulatory networks George Yiadom Osei, Joseph Adu-Amankwaah, Selina Koomson, Solomon Beletaa, Emmanuel Akomanin Asiamah, Cecilia Smith-Togobo, Siti Razila Abdul Razak Molecular Biology Reports.2023; 50(11): 9575. CrossRef
MicroRNA-552 expression in colorectal cancer and its clinicopathological significance Joon Im, Soo Kyung Nam, Hye Seung Lee Journal of Pathology and Translational Medicine.2021; 55(2): 125. CrossRef
Postoperative changes in plasma miR21‐5p as a novel biomarker for colorectal cancer recurrence: A prospective study Masahiro Fukada, Nobuhisa Matsuhashi, Takao Takahashi, Nobuhiko Sugito, Kazuki Heishima, Kazuhiro Yoshida, Yukihiro Akao Cancer Science.2021; 112(10): 4270. CrossRef
Differential expression of microRNAs in colorectal cancer: Different patterns between isolated cancer gland and stromal cells Ayaka Sato, Yasuko Fujita, Koki Otsuka, Akira Sasaki, Hiromu Suzuki, Takayuki Matsumoto, Tamotsu Sugai Pathology International.2020; 70(1): 21. CrossRef
High-Throughput Multiplex Immunohistochemical Imaging of the Tumor and Its Microenvironment Jiwon Koh, Yoonjin Kwak, Jin Kim, Woo Ho Kim Cancer Research and Treatment.2020; 52(1): 98. CrossRef
Tumor Tissue MIR92a and Plasma MIRs21 and 29a as Predictive Biomarkers Associated with Clinicopathological Features and Surgical Resection in a Prospective Study on Colorectal Cancer Patients Masahiro Fukada, Nobuhisa Matsuhashi, Takao Takahashi, Nobuhiko Sugito, Kazuki Heishima, Yukihiro Akao, Kazuhiro Yoshida Journal of Clinical Medicine.2020; 9(8): 2509. CrossRef
The promising role of noncoding RNAs in cancer-associated fibroblasts: an overview of current status and future perspectives Zengli Fang, Jin Xu, Bo Zhang, Wei Wang, Jiang Liu, Chen Liang, Jie Hua, Qingcai Meng, Xianjun Yu, Si Shi Journal of Hematology & Oncology.2020;[Epub] CrossRef
Altered miR-21, miRNA-148a Expression in Relation to KRAS Mutation Status as Indicator of Adenoma-Carcinoma Transitional Pattern in Colorectal Adenoma and Carcinoma Lesions Somayeh Igder, Javad Mohammadiasl, Pooneh Mokarram Biochemical Genetics.2019; 57(6): 767. CrossRef
Development and Validation of an Easy-to-Implement, Practical Algorithm for the Identification of Molecular Subtypes of Gastric Cancer: Prognostic and Therapeutic Implications Jiwon Koh, Keun-Wook Lee, Soo Kyung Nam, An Na Seo, Ji-Won Kim, Jin Won Kim, Do Joong Park, Hyung-Ho Kim, Woo Ho Kim, Hye Seung Lee The Oncologist.2019; 24(12): e1321. CrossRef
Prognostic Utility of Histological Growth Patterns of Colorectal Lung Oligometastasis Son Jae Yeong, Min Gyoung Pak, Hyoun Wook Lee, Seung Yeon Ha, Mee Sook Roh Journal of Pathology and Translational Medicine.2018; 52(2): 98. CrossRef
Effect of dietary components on miRNA and colorectal carcinogenesis Adewale Oluwaseun Fadaka, Babajide A. Ojo, Olusola Bolaji Adewale, Temitope Esho, Ashley Pretorius Cancer Cell International.2018;[Epub] CrossRef
Ligand-Independent Epidermal Growth Factor Receptor Overexpression Correlates with Poor Prognosis in Colorectal Cancer Sumi Yun, Yoonjin Kwak, Soo Kyung Nam, An Na Seo, Heung-Kwon Oh, Duck-Woo Kim, Sung-Bum Kang, Hye Seung Lee Cancer Research and Treatment.2018; 50(4): 1351. CrossRef
Mutation analysis of CTNNB1 gene and the ras pathway genes KRAS , NRAS , BRAF , and PIK3CA in eyelid sebaceous carcinomas Mi Jung Kwon, Eun Sook Nam, Seong Jin Cho, Hye-Rim Park, Soo Kee Min, Jinwon Seo, Ji-Young Choe Pathology - Research and Practice.2017; 213(6): 654. CrossRef
Clinicopathologic implications of immune classification by PD-L1 expression and CD8-positive tumor-infiltrating lymphocytes in stage II and III gastric cancer patients Jiwon Koh, Chan-Young Ock, Jin Won Kim, Soo Kyung Nam, Yoonjin Kwak, Sumi Yun, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Woo Ho Kim, Hye Seung Lee Oncotarget.2017; 8(16): 26356. CrossRef