RET Protein Expression in Colorectal Cancer; An Immunohistochemical Assessment

Ashkboos, Maryam; Nikbakht, Mohsen; Zarinfard, Giti; Soleimani, Mitra

doi:10.31557/apjcp.2021.22.4.1019

Cited by 4 publications

(3 citation statements)

References 11 publications

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“…Receptor tyrosine kinase is an enzyme-linked receptor involved in the proliferation and invasion of a variety of cells, and RET G533C mutation can accelerate the proliferation and invasion of CRC tumor cells. Therefore, RET has a key position in the development and progression of CRC and has been regarded theorized as a new target for its treatment [22] [23] [24] . GDNF can promote the proliferation and metastasis of malignant tumor cells through the RET-SRC-HER2 and RET-AKT signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Expression levels and diagnostic value of serum GDNF, CEA and CA199 in patients with colorectal carcinoma

Jue,

Lulu,

Yan

et al. 2024

J Med Biochemistry

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Background: To investigate the expression levels and diagnostic value of glial cell line-derived neurotrophic factor (GDNF), carcinoembryonic antigen (CEA) and carbohydrate antigen199 (CA199) in patients with colorectal carcinoma (CRC). Methods. 50 CRC patients at our hospital from Feb. 2020 to Feb. 2021 were chosen as the malignant group, another 50 patients with benign colonic diseases were chosen as the benign group, and 50 healthy people who came to our hospital for physical examination during the same period were considered as the control group. Fasting peripheral venous blood was taken from all research subjects in the morning and tested by a fully-automated electrochemiluminometer to determine the GDNF, CEA and CA199 levels. The sensitivity and specificity of the combined detection of the three indexes for CRC were analyzed, and the ROC curve was plotted to record the area under the curve (AUC). Results. The malignant group had remarkably higher CEA and CA199 levels (P<0.001) and a lower GDNF level (P<0.001) when compared with the benign and control groups. The sensitivity, specificity, positive predictive value and negative predictive value of the combined detection were 96.0%, 94.0%, 88.9% and 97.9%, respectively. The combined detection had the AUC (95% CI) = 0.950 (0.909-0.991), the standard error of 0.021, and the progressive Sig.b<0.001. Conclusion. The combined diagnosis of serum GDNF, CEA and CA199 is a reliable method to improve the diagnostic accuracy of CRC, and this strategy can effectively reduce the missed diagnosis rate and has high application value in clinic.

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Section: Discussionmentioning

confidence: 99%

Expression levels and diagnostic value of serum GDNF, CEA and CA199 in patients with colorectal carcinoma

Jue,

Lulu,

Yan

et al. 2024

J Med Biochemistry

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“…Additionally, lower plasma levels of potential tumor suppressor proteins, such as RET and ARHGEF12 were detected in CRC patients. RET, is a transmembrane receptor tyrosine kinase and a receptor for the GDNF-family ligands, which downregulation in CRC tissue compared to healthy tissue was noticed ( 58 ). CRC patients with somatic RET mutations exhibited a lower incidence of liver metastasis but a higher incidence of peritoneal metastasis and more frequently exhibited mucinous histology ( 59 ).…”

Section: Discussionmentioning

confidence: 99%

Plasma protein changes reflect colorectal cancer development and associated inflammation

Urbiola-Salvador,

Jabłońska,

Miroszewska

et al. 2023

Front. Oncol.

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IntroductionColorectal cancer (CRC) is the third most common malignancy and the second leading cause of death worldwide. Efficient non-invasive blood-based biomarkers for CRC early detection and prognosis are urgently needed.MethodsTo identify novel potential plasma biomarkers, we applied a proximity extension assay (PEA), an antibody-based proteomics strategy to quantify the abundance of plasma proteins in CRC development and cancer-associated inflammation from few μL of plasma sample.ResultsAmong the 690 quantified proteins, levels of 202 plasma proteins were significantly changed in CRC patients compared to age-and-sex-matched healthy subjects. We identified novel protein changes involved in Th17 activity, oncogenic pathways, and cancer-related inflammation with potential implications in the CRC diagnosis. Moreover, the interferon γ (IFNG), interleukin (IL) 32, and IL17C were identified as associated with the early stages of CRC, whereas lysophosphatidic acid phosphatase type 6 (ACP6), Fms-related tyrosine kinase 4 (FLT4), and MANSC domain-containing protein 1 (MANSC1) were correlated with the late-stages of CRC.DiscussionFurther study to characterize the newly identified plasma protein changes from larger cohorts will facilitate the identification of potential novel diagnostic, prognostic biomarkers for CRC.

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“…reported enhanced methylation, and therefore downregulation, of RET in CRC samples, suggesting a tumor suppressive function for RET in the CRC samples analyzed ( 192 ). The potential tumor suppressive function of RET is further supported by a 2021 study in which immunohistochemical analyses demonstrate a reduction in RET protein expression in CRC tissue when compared to adjacent normal tissue ( 193 ), suggesting an inverse correlation between RET expression and CRC development. While the opposing paradigms of RET function may present challenges in the treatment of RET-altered CRC tumors, further analyses are required to determine whether tumor-suppressive or oncogenic RET occurs in specific subpopulations of CRC tumors.…”

Section: Aberrant Ret Signaling In Tumorigenesismentioning

confidence: 92%

RET signaling pathway and RET inhibitors in human cancer

Regua

Najjar

2022

Front. Oncol.

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Rearranged during transfection (RET) receptor tyrosine kinase was first identified over thirty years ago as a novel transforming gene. Since its discovery and subsequent pathway characterization, RET alterations have been identified in numerous cancer types and are most prevalent in thyroid carcinomas and non-small cell lung cancer (NSCLC). In other tumor types such as breast cancer and salivary gland carcinomas, RET alterations can be found at lower frequencies. Aberrant RET activity is associated with poor prognosis of thyroid and lung carcinoma patients, and is strongly correlated with increased risk of distant metastases. RET aberrations encompass a variety of genomic or proteomic alterations, most of which confer constitutive activation of RET. Activating RET alterations, such as point mutations or gene fusions, enhance activity of signaling pathways downstream of RET, namely PI3K/AKT, RAS/RAF, MAPK, and PLCγ pathways, to promote cell proliferation, growth, and survival. Given the important role that mutant RET plays in metastatic cancers, significant efforts have been made in developing inhibitors against RET kinase activity. These efforts have led to FDA approval of Selpercatinib and Pralsetinib for NSCLC, as well as, additional selective RET inhibitors in preclinical and clinical testing. This review covers the current biological understanding of RET signaling, the impact of RET hyperactivity on tumor progression in multiple tumor types, and RET inhibitors with promising preclinical and clinical efficacy.

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RET Protein Expression in Colorectal Cancer; An Immunohistochemical Assessment

Abstract: an epigenome fraught with methylated genes. CIMP CRCs are associated with older age, female gender, family history of CRC, proximal location in the colon, and mucinous cell differentiation (Weisenberger et al.,

Cited by 4 publications

References 11 publications

Expression levels and diagnostic value of serum GDNF, CEA and CA199 in patients with colorectal carcinoma

Expression levels and diagnostic value of serum GDNF, CEA and CA199 in patients with colorectal carcinoma

Plasma protein changes reflect colorectal cancer development and associated inflammation

RET signaling pathway and RET inhibitors in human cancer

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