Abstract
Frizzled homolog 3 receptor was up-regulated in several gastrointestinal cancers such as esophageal and gastric cancers. Moreover, frizzled homolog 3 has recently reported to be expressed in colorectal adenoma specimens. In the present study, we investigated the clinical significance of frizzled homolog 3 protein in colorectal cancer patients. Using immunocytochemical staining, frizzled homolog 3 expression was examined in 186 colorectal cancer specimens, 79 colorectal adenoma specimens, 133 colorectal polyp specimens, 127 colorectal cancer specimens with lymph node and/or distant metastasis, 310 specimens of various non-colorectal cancer metastatic carcinomas and 40 specimens with simultaneous occurrence of colorectal cancer, colorectal adenoma and colorectal polyp. Statistical analysis was used to correlate frizzled homolog 3 protein expression to the clinicohistopathological factors, recurrence/metastasis and survival after follow-up for 42 months in colorectal cancer patients. Frizzled homolog 3 protein was expressed in 100% colorectal cancer specimens, 89% colorectal adenoma specimens, 75% colorectal polyp specimens and 69% normal colorectal epithelial tissues. Moreover, frizzled homolog 3 immunocytochemical scores were highly correlated with colorectal cancer progression. Furthermore, frizzled homolog 3 was expressed in a comparatively lower percentage of metastatic hepatocellular carcinoma and metastatic renal clear cell carcinoma with focal and very weak staining than other metastatic tumor types. On the other hand, the frizzled homolog 3 immunocytochemical scores of colorectal adenomas with synchronous colorectal carcinomas were significantly higher than those of pure colorectal adenomas. Statistical analysis showed that frizzled homolog 3 immunocytochemical scores were associated with Dukes stage and lymph node status. Finally, stratified groups of colorectal cancer patients had significant differences in their recurrence/metastasis and survival. In conclusion, the present large-scale study has clearly showed that frizzled homolog 3 protein can generate clinically important information for colorectal cancer patients.
Highlights
Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide, accounting for more than 1 million cases and 600,000 deaths every year [1]
FZD3 protein has a predominant role in Wnt-induced neurite outgrowth in Ewing sarcoma tumor cells [25] and it is highly expressed in poorly differentiated squamous cell esophageal carcinoma tissues [16]
FZD3 protein expression in colorectal adenoma (CAD) as shown by us matches with those of a previous study that FZD3 mRNA expressed in 79% (11/14) CAD specimens with a median fold change of 6.5 [26]
Summary
Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide, accounting for more than 1 million cases and 600,000 deaths every year [1]. Tight control of Wnt signaling is crucial for the correct orchestration of development and aberrant constitutive activation of the Wnt signaling pathway will lead to uncontrolled cell proliferation, growth and survival, promoting the development of cancer [9]. The binding of Wnt ligands to their cellsurface receptors transduces intracellular signals through either canonical or non-canonical Wnt-signaling pathway. In the canonical Wnt signaling pathway, Wnts bind to a complex of FZD and low-density lipoprotein-related receptors 5 and 6 [12,13,14]. The non-canonical Wnt signaling pathway consists of the Wnt/Ca2+ pathway and Wnt/c-Jun N-terminal kinase (planar cell polarity) pathway and Wnts bind to a complex comprised of FZD, receptor tyrosine kinase-like orphan receptor 2/receptor related to tyrosine kinase for activation of downstream signaling [12,13,14]. FZD plays a crucial role in both canonical and non-canonical pathways
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
