High FRMD3 expression is prognostic for worse survival in rectal cancer patients treated with CCRT

Chen, Tzu‐Ju; Chou, Chia-Lin; Tian, Yufeng; Yeh, Cheng-Fa; Chan, Ti‐Chun; He, Hao; Li, Wan-Shan; Tsai, Huey‐Pin; Li, Chien‐Feng; Lai, Hong-Yue

doi:10.1007/s10147-021-01944-6

Cited by 9 publications

(12 citation statements)

References 46 publications

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“…In cell experiments the authors could show that it was able to induce apoptosis via the extrinsic, i.e., membrane dependent, pathway [ 15 ]. In contrast, reports on rectal [ 38 , 39 ] and colon cancer [ 40 ] revealed that up-regulation of FRMD3 was associated with worse response to chemoradiotherapy. In two of the mentioned studies this molecule formed part of a multi-gene signature [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 94%

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Hsa-miR-3651 could serve as a novel predictor for in-breast recurrence via FRMD3

et al. 2021

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Background MicroRNAs are small non-coding RNAs with pivotal regulatory functions in multiple cellular processes. Their significance as molecular predictors for breast cancer was demonstrated in the past 15 years. The aim of this study was to elucidate the role of hsa-miR-3651 for predicting of local control (LC) in early breast cancer. Results By means of high-throughput technology, hsa-miR-3651 was found to be differentially expressed between patients who experienced local relapse compared to those without (N = 23; p = 0.0035). This result could be validated in an independent cohort of 87 patients using RT-qPCR (p < 0.0005). In a second analysis step with a chip-based microarray containing 70,523 probes of potential target molecules, FERM domain protein 3 (FRMD3) was found to be the most down-regulated protein (N = 21; p = 0.0016). Computational analysis employing different prediction algorithms revealed FRMD3 as a likely downstream target of hsa-miR-3651 with an 8mer binding site between the two molecules. This could be validated in an independent patient set (N = 20, p = 0.134). Conclusion The current study revealed that hsa-miR-3651 is a predictor of LC in early breast cancer via its putative target protein FRMD3. Since microRNAs interfere in multiple pathways, the results of this hypothesis generating study may contribute to the development of tailored therapies for breast cancer in the future.

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Section: Discussionmentioning

confidence: 94%

“…In two of the mentioned studies this molecule formed part of a multi-gene signature [ 39 , 40 ]. In the third analysis, it was found to be the most up-regulated gene in nonresponders among 172 patients receiving cCRT [ 38 ]. Unfortunately, the authors did not verify their results in an independent set of individuals.…”

Section: Discussionmentioning

confidence: 99%

Hsa-miR-3651 could serve as a novel predictor for in-breast recurrence via FRMD3

et al. 2021

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“…The FRMD3 gene was identified as a novel putative tumor suppressor in non-small cell lung cancer ( 33 ). However, high FRMD3 expression in patients with rectal carcinomatosis is associated with unfavorable prognosis ( 39 ). In this study, The mRNA and protein expression levels of FRMD3 were significantly elevated in THCA tissues, implying that FRMD3, similar to CDH2, plays a tumor-promoting function in THCA.…”

Section: Discussionmentioning

confidence: 99%

Roles of Cadherin2 in Thyroid Cancer

et al. 2022

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BackgroundThe majority of drug-resistant cells in Thyroid cancer (THCA) tend to exhibit an Epithelial mesenchymal transition (EMT) phenotype, and abnormal expression of the cell adhesion molecule Cadherin2 (CDH2) is a hallmark of EMT. However, the roles of CDH2 in THCA and its underlying mechanisms are unknown.MethodsWe analyzed the CDH2 expression in The Cancer Genome Atlas (TCGA) database and screened for genes positively associated with CDH2. Small interfering RNA and cell transfection were used for knocking down CDH2 in THCA cells, cell counting kit-8 (CCK-8) assay and immunofluorescence to detect cell proliferation. Binding miRNAs of CDH2 and CDH2-associated genes were predicted using the Encyclopedia of RNA Interactomes (ENCORI) database. The expression of genes in clinical THCA tissues was investigated from the Human Protein Atlas (HPA) database and validated by qRT-PCR. We conducted the cell functions pathways of CDH2 and CDH2-associated gene FRMD3 by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. We also showed the correlation between CDH2 and FRMD3 expression and tumor immune infiltration.ResultsThe expression of CDH2 was significantly higher in THCA tumor tissues compared to normal tissues. Moreover, there were strongly associations of CDH2 expression with the stages T and N. Cellular function assays showed that CDH2 exerted its growth-promoting activity of THCA. To better understand how CDH2 was regulated in THCA, we sought genes associated with CDH2. Correlation analysis revealed that there were negative correlations between genes (CDH2, FRMD3) and miRNAs (hsa-miR-410-3p, hsa-miR-411-5p, hsa-miR-299-5p). Moreover, CDH2 and FRMD3 expression were significantly higher in tumor tissues than in normal tissues, while hsa-miR-410-3p, hsa-miR-411-5p and hsa-miR-299-5p were significantly decreased in tumor tissues compared with normal tissues in THCA. GO and KEEG results showed that CDH2 and FRMD3 were strongly associated with immune-related functions. High expression of CDH2 and FRMD3 was linked to the suppression of immune cells. There were strong negativity correlations between CDH2, FRMD3 and T-cell exhaustion factors.ConclusionOur data indicated that CDH2 and CDH2-related gene FRMD3 might have the critical effects on altering tumors becoming ‘cold tumors’ eventually leading to immune checkpoint inhibitor resistance.

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“…However, little is known about FRMD3 in brain cancer. A previous study of FRMD3 mentioned that high levels of FRMD3 in rectal cancer lead to a poor disease survival rate [ 45 ]. FRMD3 was also found to be a candidate TSG in lung cancer and acute myeloid leukemia [ 43 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study Identifies Multiple Susceptibility Loci for Malignant Neoplasms of the Brain in Taiwan

Lin

Yang

et al. 2022

JPM

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Primary brain malignancy is a rare tumor with a global incidence of less than 10 per 100,000 people. Hence, there is limited power for identifying risk loci in individual studies, especially for Han Chinese. We performed a genome-wide association study (GWAS) in Taiwan, including 195 cases and 195 controls. We identified five new genes for malignant neoplasms of the brain: EDARADD (rs645507, 1p31.3, p = 7.71 × 10−5, odds ratio (OR) = 1.893), RBFOX1 (rs8044700, p = 2.35 × 10−5, OR = 2.36), LMF1 (rs3751667, p = 7.24 × 10−7, OR = 2.17), DPP6 (rs67433368, p = 8.32 × 10−5, OR = 3.94), and NDUFB9 (rs7827791, p = 9.73 × 10−6, OR = 4.42). These data support that genetic susceptibility toward GBM or non-GBM tumors is highly distinct, likely reflecting different etiologies. Combined with signaling analysis, we found that RNA modification may be related to major risk factors in primary malignant neoplasms of the brain.

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High FRMD3 expression is prognostic for worse survival in rectal cancer patients treated with CCRT

Cited by 9 publications

References 46 publications

Hsa-miR-3651 could serve as a novel predictor for in-breast recurrence via FRMD3

Hsa-miR-3651 could serve as a novel predictor for in-breast recurrence via FRMD3

Roles of Cadherin2 in Thyroid Cancer

Genome-Wide Association Study Identifies Multiple Susceptibility Loci for Malignant Neoplasms of the Brain in Taiwan

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