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pmid:39596188

Identifying an Inversin as a Novel Prognostic Marker in Patients with Clear-Cell Renal Cell Carcinoma.

Ivanka Urlić · Violeta Šoljić · Martina Vukoja · Inga Marijanović · Marija Kraljević · Marjan Urlić · Sara Marić · Katarina Vukojević · Natalija Filipović

International journal of molecular sciences · 2024 doi:10.3390/ijms252212120

Paper

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Experiment

complete

Data

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Analysis

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title
Identifying an Inversin as a Novel Prognostic Marker in Patients with Clear-Cell Renal Cell Carcinoma.
doi
10.3390/ijms252212120
pmid
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Ivanka Urlić
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Violeta Šoljić
[2]
Martina Vukoja
[3]
Inga Marijanović
[4]
Marija Kraljević
[5]
Marjan Urlić
[6]
Sara Marić
[7]
Katarina Vukojević
[8]
Natalija Filipović
journal
International journal of molecular sciences
year
2024
abstract
Precision medicine is a developing trend in oncology, and it includes the prognosis and treatment of advanced-stage ccRCC. New predictive factors and therapeutic targets for this disease are steadily needed. The aim of this study was to explore the tumor expression of inversin as a potential prognostic factor and/or therapeutic target in ccRCC. We compared the expression of inversin between primary ccRCC and normal renal tissues by using immunohistochemistry and rtPCR in our cohort, and we also analyzed publicly available data from the TCGA-KIRC cohort. We found that the expression of inversin was significantly lower in primary tumor tissue, in comparison to solid normal tissue. Data from the KIRC study confirmed that a lower INVS expression level in ccRCC was significantly related with the overall and disease-specific survival, as well as with a shorter progression-free interval (p < 0.05). Four out of ten inversin interactome partners were significantly related with the overall and disease-specific survival in ccRCC. A lower expression of ANKS6 was a negative survival predictor, while a higher expression of NPHP3, DVL1, or DVL3 was related with a lower survival. The expression of INVS and its interactome partners in ccRCC was correlated with the differentiation of the tumor and metastasis. The expression of INVS and its partners was also correlated with tumor leukocyte infiltration and the expression of immune checkpoint genes. The results of this study point to inversin and a distinguished group of its interactome partners as potential prognostic factors in ccRCC, with their predominant involvement in the modulation of the inflammatory infiltration of the tumor microenvironment and a strong relationship with the metastatic potential of the tumor.
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Data from the primary tumor (533 samples) were used for a Kaplan–Meyer curve analysis. The median was used as the cut-off value. The different Kaplan–Meier curves were compared using the log-rank test and χ2, and the p-values (χ2 distribution) were reported. A differential expression analysis using Welch’s t-test was made to compare the M1 (N = 79) vs. M0 (N = 422) pathological M stages (for data with a known M stage). A one-way ANOVA was used to compare expression data according to a histological grade, after GX (N = 5) and null (N = 3) specimens were removed.
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Data from the primary tumor (533 samples) were used for a Kaplan–Meyer curve analysis. The median was used as the cut-off value. The different Kaplan–Meier curves were compared using the log-rank test and χ2, and the p-values (χ2 distribution) were reported. A differential expression analysis using Welch’s t-test was made to compare the M1 (N = 79) vs. M0 (N = 422) pathological M stages (for data with a known M stage). A one-way ANOVA was used to compare expression data according to a histological grade, after GX (N = 5) and null (N = 3) specimens were removed.
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://docs.gdc.cancer.gov/Data/Release_Notes/Data_Release_Notes/#data-release-400; https://gdc-hub.s3.us-east-1.amazonaws.com/download/TCGA-KIRC.star_fpkm-uq.tsv.gz; Full metadata, TCGA_KIRC_exp_HiSeqV2; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE131685, GSE131685.
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Data from the KIRC study confirmed that a lower INVS expression level in ccRCC was significantly related with the overall and disease-specific survival, as well as with a shorter progression-free interval (p < 0.05).
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Data from the KIRC study confirmed that a lower INVS expression level in ccRCC was significantly related with the overall and disease-specific survival, as well as with a shorter progression-free interval (p < 0.05).
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Data from the primary tumor (533 samples) were used for a Kaplan–Meyer curve analysis. The median was used as the cut-off value. The different Kaplan–Meier curves were compared using the log-rank test and χ2, and the p-values (χ2 distribution) were reported. A differential expression analysis using Welch’s t-test was made to compare the M1 (N = 79) vs. M0 (N = 422) pathological M stages (for data with a known M stage). A one-way ANOVA was used to compare expression data according to a histological grade, after GX (N = 5) and null (N = 3) specimens were removed.
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Data from the primary tumor (533 samples) were used for a Kaplan–Meyer curve analysis. The median was used as the cut-off value. The different Kaplan–Meier curves were compared using the log-rank test and χ2, and the p-values (χ2 distribution) were reported. A differential expression analysis using Welch’s t-test was made to compare the M1 (N = 79) vs. M0 (N = 422) pathological M stages (for data with a known M stage). A one-way ANOVA was used to compare expression data according to a histological grade, after GX (N = 5) and null (N = 3) specimens were removed.
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New predictive factors and therapeutic targets for this disease are steadily needed. The aim of this study was to explore the tumor expression of inversin as a potential prognostic factor and/or therapeutic target in ccRCC. We compared the expression of inversin between primary ccRCC and normal renal tissues by using immunohistochemistry and rtPCR in our cohort, and we also analyzed publicly available data from the TCGA-KIRC cohort. We found that the expression of inversin was significantly lower in primary tumor tissue, in comparison to solid normal tissue. Data from the KIRC study confirmed that a lower INVS expression level in ccRCC was significantly related with the overall and disease-specific survival, as well as with a shorter progression-free interval (p < 0.05). Four out of ten inversin interactome partners were significantly related with the overall and disease-specific survival in ccRCC. A lower expression of ANKS6 was a negative survival predictor, while a higher expression of NPHP3, DVL1, or DVL3 was related with a lower survival. The expression of INVS and its interactome partners in ccRCC was correlated with the differentiation of the tumor and metastasis. The expression of INVS and its partners was also correlated with tumor leukocyte infiltration and the expression of immune checkpoint genes. The results of this study point to inversin and a distinguished group of its interactome partners as potential prognostic factors in ccRCC, with their predominant involvement in the modulation of the inflammatory infiltration of the tumor microenvironment and a strong relationship with the metastatic potential of the tumor.", "claims": [{"id": "claim-method", "statement": "Data from the primary tumor (533 samples) were used for a Kaplan–Meyer curve analysis. The median was used as the cut-off value. 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