Clinicopathological and Molecular Prognostic Classifier for Intermediate/High-Risk Clear Cell Renal Cell Carcinoma

Roldán, Fiorella L.; Lozano, Juan José; Ingelmo-Torres, Mercedes; Carrasco, Raquel Castellano; Díaz, Esther; Ramírez‐Backhaus, M.; Rubio, José; Reig, Òscar; Alcaraz, Antonio; Mengual, Lourdes; Izquierdo, Laura

doi:10.3390/cancers13246338

Cited by 3 publications

(4 citation statements)

References 39 publications

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“…Another study illustrated that HS6ST2 was upregulated in NSCLC 22 and promoted cell development in NSCLC 23 . Our findings in renal clear cell cancer contradict those of earlier studies 17 , which showed that HS6ST2 is a potential prognostic biomarker and that inhibition of HS6ST2 causes decreased migration and invasion of RCC cells 18 . This inconsistency is likely attributable to the fact that earlier studies placed a greater emphasis on RCC cell lines with high metastatic ability.…”

Section: Discussioncontrasting

confidence: 99%

“…Another study illustrated that HS6ST2 was highly expressed in papillary thyroid cancer, thyroid cancer, and high-grade cartilage tumor tissues 12 , though it was expressed at low levels in glioma tissues 13 , and HS6ST2 was also found to promote the development of thyroid cancer 14 , 15 . HS6ST2 expression was found to be negatively related to OS and was an independent prognostic factor for clear cell renal cell carcinoma patient outcomes 16 , 17 . Furthermore, HS6ST2 can be downregulated by miR-145-5p, limiting the development of renal cell carcinoma (RCC) cells 18 .…”

Section: Introductionmentioning

confidence: 94%

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Pancancer analysis of the correlations of HS6ST2 with prognosis, tumor immunity, and drug resistance

Chen,

Li,

Jiang

et al. 2023

Sci Rep

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HS6ST2 has ability to encodes a member of the heparan sulfate (HS) sulfotransferase gene family, which catalyze the transfer of sulfate to HS and a crucial regulator of cell growth, differentiation, adhesion, and migration. Although mounting evidence supports a vital role for HS6ST2 in tumorigenesis of some cancers, no pan-cancer analysis of HS6ST2 has been reported. Therefore, we aimed to explore the prognostic value of HS6ST2 in 33 cancer types and investigate its potential immune function. Based on data from The Cancer Genome Atlas, Cancer Cell Lines Encyclopedia, Genotype Tissue Expression, and GSCA, we used a range of bioinformatics approaches to explore the potential carcinogenic role of HS6ST2, analysis of HS6ST2 and prognosis, DNA methylation, RNA methylation, microsatellite instability (MSI), tumor mutation burden (TMB), and immune cell infiltration in different tumors. The results show that HS6ST2 was highly expressed in most cancers but lower in Breast invasive carcinoma, Kidney Chromophobe, Kidney renal clear cell carcinoma, Kidney renal papillary cell carcinoma, and Uterine Corpus Endometrial Carcinoma. Moreover, HS6ST2 is positively or negatively associated with prognosis in different cancers. HS6ST2 expression was not only associated with MSI in 5 cancer types and associated with TMB in 10 cancer types, and it's significantly correlated with DNA methylation in 13 types of cancer, but it's correlated with RNA methylation related genes in most cancer. HS6ST2 expression was correlated with immune cell infiltration, immune-related genes, tumor immune microenvironment, and drug resistance in various cancers. Eventually, HS6ST2 was validated in human lung adenocarcinoma tissues. Our study reveals that HS6ST2 can function as a prognostic marker in various malignant tumors because of its role in tumorigenesis and tumor immunity.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Pancancer analysis of the correlations of HS6ST2 with prognosis, tumor immunity, and drug resistance

Chen,

Li,

Jiang

et al. 2023

Sci Rep

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“…Its overexpression promotes cell viability, proliferation and invasion, it is involved in the PI3K/AKT pathway [ 36 ] and is part of an immune prognostic signature for colon and rectal cancer [ 35 ]. HS6ST2 (heparan sulfate D-glucosaminyl 6- O -sulfotransferase-2) is a glycolysis-related gene and has also been associated with poor disease outcomes in numerous malignancies [ 10 , 37 ]. Interestingly, our group previously validated this gene as an independent prognosis biomarker in intermediate/high-risk ccRCC and found it to be associated with angiogenesis, epithelia–mesenchymal transition (EMT), and indirectly related to the PD-1, PDL-1 cancer immunotherapy pathway [ 37 , 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…HS6ST2 (heparan sulfate D-glucosaminyl 6- O -sulfotransferase-2) is a glycolysis-related gene and has also been associated with poor disease outcomes in numerous malignancies [ 10 , 37 ]. Interestingly, our group previously validated this gene as an independent prognosis biomarker in intermediate/high-risk ccRCC and found it to be associated with angiogenesis, epithelia–mesenchymal transition (EMT), and indirectly related to the PD-1, PDL-1 cancer immunotherapy pathway [ 37 , 38 , 39 ]. MIA2 (melanoma inhibitory activity 2) has been found in several malignancies and can act as a tumor suppressor [ 40 ] or as a proto-oncogene depending on the receptor-related signaling differences [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Gene Expression-Based Signature in Clear-Cell Renal Cell Carcinoma

Roldán

Izquierdo

Ingelmo-Torres

et al. 2022

Cancers

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The inaccuracy of the current prognostic algorithms and the potential changes in the therapeutic management of localized ccRCC demands the development of an improved prognostic model for these patients. To this end, we analyzed whole-transcriptome profiling of 26 tissue samples from progressive and non-progressive ccRCCs using Illumina Hi-seq 4000. Differentially expressed genes (DEG) were intersected with the RNA-sequencing data from the TCGA. The overlapping genes were used for further analysis. A total of 132 genes were found to be prognosis-related genes. LASSO regression enabled the development of the best prognostic six-gene panel. Cox regression analyses were performed to identify independent clinical prognostic parameters to construct a combined nomogram which includes the expression of CERCAM, MIA2, HS6ST2, ONECUT2, SOX12, TMEM132A, pT stage, tumor size and ISUP grade. A risk score generated using this model effectively stratified patients at higher risk of disease progression (HR 10.79; p < 0.001) and cancer-specific death (HR 19.27; p < 0.001). It correlated with the clinicopathological variables, enabling us to discriminate a subset of patients at higher risk of progression within the Stage, Size, Grade and Necrosis score (SSIGN) risk groups, pT and ISUP grade. In summary, a gene expression-based prognostic signature was successfully developed providing a more precise assessment of the individual risk of progression.

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Development and validation of intravoxel incoherent motion diffusion weighted imaging-based model for preoperative distinguishing nuclear grade and survival of clear cell renal cell carcinoma complicated with venous tumor thrombus

Zhao,

Xu,

et al. 2024

Cancer Imaging

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Objective To assess the utility of multiparametric MRI and clinical indicators in distinguishing nuclear grade and survival of clear cell renal cell carcinoma (ccRCC) complicated with venous tumor thrombus (VTT). Materials and methods This study included 105 and 27 patients in the training and test sets, respectively. Preoperative MRI, including intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), was performed. Renal lesions were evaluated for IVIM-DWI metrics and conventional MRI features. All the patients had postoperative histologically proven ccRCC and VTT. An expert uropathologist reviewed all specimens to confirm the nuclear grade of the World Health Organization/ International Society of Urological Pathology (WHO/ISUP) of the tumor. Univariate and multivariable logistic regression analyses were used to select the preoperative imaging features and clinical indicators. The predictive ability of the logistic regression model was assessed using receiver operating characteristic (ROC) analysis. Survival curves were plotted using the Kaplan–Meier method. Results High WHO/ISUP nuclear grade was confirmed in 69 of 105 patients (65.7%) in the training set and 19 of 27 patients (70.4%) in the test set, respectively (P = 0.647). Dp_ROI_Low, tumor size, serum albumin, platelet count, and lymphocyte count were independently related to high WHO/ISUP nuclear grade in the training set. The model identified high WHO/ISUP nuclear grade well, with an AUC of 0.817 (95% confidence interval [CI]: 0.735–0.899), a sensitivity of 70.0%, and a specificity of 77.8% in the training set. In the independent test set, the model demonstrated an AUC of 0.766 (95% CI, 0.567–0.966), a sensitivity of 79.0%, and a specificity of 75.0%. Kaplan–Meier analysis showed that the predicted high WHO/ISUP nuclear grade group had poorer progression-free survival than the low WHO/ISUP nuclear grade group in both the training and test sets (P = 0.001 and P = 0.021). Conclusions IVIM-DWI-derived parameters and clinical indicators can be used to differentiate nuclear grades and predict progression-free survival of ccRCC and VTT.

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Clinicopathological and Molecular Prognostic Classifier for Intermediate/High-Risk Clear Cell Renal Cell Carcinoma

Cited by 3 publications

References 39 publications

Pancancer analysis of the correlations of HS6ST2 with prognosis, tumor immunity, and drug resistance

Pancancer analysis of the correlations of HS6ST2 with prognosis, tumor immunity, and drug resistance

Prognostic Gene Expression-Based Signature in Clear-Cell Renal Cell Carcinoma

Development and validation of intravoxel incoherent motion diffusion weighted imaging-based model for preoperative distinguishing nuclear grade and survival of clear cell renal cell carcinoma complicated with venous tumor thrombus

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