Association between prognostic survival of human colorectal carcinoma and ZNRF3 expression

Yu, Nanhui; Zhu, Hong; Tao, Yiming; Huang, Yongpan; Song, Xiangping; Zhou, Yuan; Li, Yuqiang; Pei, Qian; Tan, Qiongrong; Pei, Haiping

doi:10.2147/ott.s108134

Cited by 8 publications

(7 citation statements)

References 21 publications

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“…Basham et al reported ZNRF3 homeostatic regulation of the adrenal cortex, showing that its loss leads to severe adrenocortical hyperplasia [ 68 ]. In the same way as the ATRX gene, multiple cohorts have reported the role of ZNRF3 in tumorigenesis and its prognostic value in different malignancies [ 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ].…”

Section: Discussionmentioning

confidence: 99%

Low Protein Expression of both ATRX and ZNRF3 as Novel Negative Prognostic Markers of Adult Adrenocortical Carcinoma

Brondani

Lacombe

Mariani

et al. 2021

IJMS

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Adrenocortical carcinoma (ACC) is a rare malignancy that is associated with a dismal prognosis. Pan-genomic studies have demonstrated the involvement of ATRX and ZNRF3 genes in adrenocortical tumorigenesis. Our aims were to evaluate the protein expression of ATRX and ZNRF3 in a cohort of 82 adults with ACC and to establish their prognostic value. Two pathologists analyzed immuno-stained slides of a tissue microarray. The low protein expression of ATRX and ZNRF3 was associated with a decrease in overall survival (OS) (p = 0.045, p = 0.012, respectively). The Cox regression for ATRX protein expression of >1.5 showed a hazard ratio (HR) for OS of 0.521 (95% CI 0.273–0.997; p = 0.049) when compared with ≤1.5; for ZNRF3 expression >2, the HR for OS was 0.441 (95% CI, 0.229–0.852; p = 0.015) when compared with ≤2. High ATRX and ZNRF3 protein expressions were associated with optimistic recurrence-free survival (RFS) (p = 0.027 and p = 0.005, respectively). The Cox regression of RFS showed an HR of 0.332 (95%CI, 0.111–0.932) for ATRX expression >2.7 (p = 0.037), and an HR of 0.333 (95%CI, 0.140–0.790) for ZNRF3 expression >2 (p = 0.013). In conclusion, low protein expression of ATRX and ZNRF3 are negative prognostic markers of ACC; however, different cohorts should be evaluated to validate these findings.

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Section: Discussionmentioning

confidence: 99%

Low Protein Expression of both ATRX and ZNRF3 as Novel Negative Prognostic Markers of Adult Adrenocortical Carcinoma

Brondani

Lacombe

Mariani

et al. 2021

IJMS

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“…Ting Xu et al. also found that RNF43 mutation was enriched in BRAF V600E mutant mCRC patients who benefited from combination therapy with EGFR/BRAF inhibitors of different lines treatment ( 24 ). In the above PFS analysis of public cohort, we found that all patients with records were treated with chemotherapy± antiangiogenic agents as first-line treatment.…”

Section: Discussionmentioning

confidence: 99%

RNF43 is associated with genomic features and clinical outcome in BRAF mutant colorectal cancer

Shang

Song

et al. 2023

Front. Oncol.

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BackgroundColorectal cancer (CRC) patients with BRAF mutation have very poor prognosis. It is urgent to search for prognostic factors of BRAF mutant CRC. RNF43 is a ENF ubiquitin ligase of Wnt signaling. Mutation of RNF43 has been observed frequently in various types of human cancers. However, few studies have evaluated the role of RNF43 in CRC. The present study aimed to explore the impact of RNF43 mutations on molecular characteristics and prognosis in BRAF mutant CRC.MethodsSamples of 261 CRC patients with BRAF mutation were retrospectively analyzed. Tumor tissue and matched peripheral blood samples were collected and subjected to targeted sequencing with a panel of 1021 cancer-related genes. The association of molecular characteristics and survival in patients were then analyzed. 358 CRC patients with BRAF mutation from the cBioPortal dataset were used for further confirmation.ResultsThis study was inspired by a CRC patient with BRAF V600E and RNF43 co-mutation, who achieved a best remission of 70% and a progression free survival (PFS) of 13 months. Genomic analysis indicated that RNF43 mutation affected the genomic characteristics of patients with BRAF mutation, including microsatellite instability (MSI), tumor mutation burden (TMB) and the proportion of common gene mutations. Survival analysis showed that RNF43 mutation was a predictive biomarker for better PFS and OS in BRAF mutant CRC.ConclusionCollectively, we identified that RNF43 mutations were correlated with favorable genomic features, resulting in a better clinical outcome for BRAF mutant CRC patients.

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“…The coefficient of CDC20 in our model is positive which means the higher CDC20 expression is, the higher the risk score will be, which is consistent with the previous researches. As for ZNRF3, a higher expression of ZNRF3 was found to be related with a better survival in colorectal carcinoma [48], while its role in ccRCC has not been elucidated. As its coefficient in our model is not only positive but also large, ZNRF3 may also play an important role in ccRCC.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Role of the Ubiquitin Proteasome System in Clear Cell Renal Cell Carcinoma: A Bioinformatic Perspective

Guo¹,

Li²,

Liu³

et al. 2021

J. Cancer

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Background: Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor of the urinary system. The ubiquitin proteasome system (UPS) plays an important role in the generation, metabolism and survival of tumor. We are aimed to make a comprehensive exploration of the UPS's role in ccRCC with bioinformatic tools, which may contribute to the understanding of UPS in ccRCC, and give insight for further research. Methods: The UPS-related genes (UPSs) were collected by an integrative approach. The expression and clinical data were downloaded from TCGA database. R soft was used to perform the differentially expressed UPSs analysis, functional enrichment analysis. We also estimated prognostic value of each UPS with the help of GEPIA database. Two predicting models were constructed with the differentially expressed UPSs and prognosis-related genes, respectively. The correlations of risk score with clinical characteristics were also evaluated. Data of GSE29609 cohort were obtained from GEO database to validate the prognostic models. Results: We finally identified 91 differentially expressed UPSs, 48 prognosis related genes among them, and constructed a prognostic model with 18 UPSs successfully, the AUC was 0.760. With the help of GEPIA, we found 391 prognosis-related UPSs, accounting for 57.84% of all UPSs. Another prognostic model was constructed with 28 prognosis-related genes of them, and with a better AUC of 0.825. Additionally, our models can also stratify patients into high and low risk groups accurately in GSE29609 cohort. Similar prognostic values of our models were observed in the validated GSE29609 cohort. Conclusions: UPS is dysregulated in ccRCC. UPS related genes have significant prognostic value in ccRCC. Models constructed with UPSs are effective and applicable. An abnormal ubiquitin proteasome system should play an important role in ccRCC and be worthy of further study.

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Association between prognostic survival of human colorectal carcinoma and ZNRF3 expression

Cited by 8 publications

References 21 publications

Low Protein Expression of both ATRX and ZNRF3 as Novel Negative Prognostic Markers of Adult Adrenocortical Carcinoma

Low Protein Expression of both ATRX and ZNRF3 as Novel Negative Prognostic Markers of Adult Adrenocortical Carcinoma

RNF43 is associated with genomic features and clinical outcome in BRAF mutant colorectal cancer

Prognostic Role of the Ubiquitin Proteasome System in Clear Cell Renal Cell Carcinoma: A Bioinformatic Perspective

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