scholarly journals Beta-1,4-galactosyltransferase II predicts poor prognosis of patients with non-metastatic clear-cell renal cell carcinoma

Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769141 ◽  
Author(s):  
Haijian Zhang ◽  
Yidong Liu ◽  
Huyang Xie ◽  
Qiang Fu ◽  
Zheng Liu ◽  
...  

Beta-1,4-galactosyltransferase II is found to be associated with the alterations of tumor-related glycosylation. However, the clinical significance of beta-1,4-galactosyltransferase II in non-metastatic clear-cell renal cell carcinoma has not been reported up to now. Herein, our researches suggested that the expression level of beta-1,4-galactosyltransferase II was first found to be positively associated with tumor size, Fuhrman grade, lymphovascular invasion, rhabdoid differentiation, tumor necrosis and poor overall survival and recurrence-free survival of patients with non-metastatic clear-cell renal cell carcinoma, both in training set and validation set. Moreover, beta-1,4-galactosyltransferase II expression was identified as an independent adverse prognosticator for overall survival and recurrence-free survival of patients with non-metastatic clear-cell renal cell carcinoma. Ultimately, prognostic accuracy of the nomogram integrating beta-1,4-galactosyltransferase II with other independent prognostic parameters was dramatically improved for overall survival and recurrence-free survival of patients with non-metastatic clear-cell renal cell carcinoma. Taken together, beta-1,4-galactosyltransferase II is a potential independent adverse prognostic factor for postoperative recurrence and survival, which could be developed as a useful biomarker for non-metastatic clear-cell renal cell carcinoma by a series of further independent and retrospective studies, so as to help the postsurgical management of clear-cell renal cell carcinoma patients.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jazmine Arévalo ◽  
David Lorente ◽  
Enrique Trilla ◽  
María Teresa Salcedo ◽  
Juan Morote ◽  
...  

AbstractClear cell renal cell carcinoma (ccRCC) is the most frequent and aggressive subtype of renal carcinoma. So far, the basis of its oncogenesis remains unclear resulting in a deficiency of usable and reliable biomarkers for its clinical management. Previously, we showed that nuclear expression of the signal transducer and activator of transcription 3 (STAT3), phosphorylated at its serine 727 (pS727), was inversely proportional to the overall survival of ccRCC patients. Therefore, in the present study, we validated the value of pS727-STAT3 as a clinically relevant biomarker in ccRCC. This work is a retrospective study on 82 ccRCC patients treated with nephrectomy and followed-up for 10 years. Immunohistochemical expression of pS727-STAT3 was analyzed on a tissue microarray and nuclear and cytosolic levels were correlated with clinical outcome of patients. Our results showed that pS727-STAT3 levels, whether in the nucleus (p = 0.002; 95% CI 1.004–1.026) or the cytosol (p = 0.040; 95% CI 1.003–1.042), significantly correlate with patients’ survival in an independent-manner of clinicopathological features (Fuhrman grade, risk group, and tumor size). Moreover, we report that patients with high pS727-STAT3 levels who undergone adjuvant therapy exhibited a significant stabilization of the disease (~ 20 months), indicating that pS727-STAT3 can pinpoint a subset of patients susceptible to respond well to treatment. In summary, we demonstrated that high pS727-STAT3 levels (regardless of their cellular location) correlate with low overall survival of ccRCC patients, and we suggested the use of pS727-STAT3 as a prognostic biomarker to select patients for adjuvant treatment to increase their survival.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4522-4522
Author(s):  
Kimryn Rathmell ◽  
Samira A Brooks ◽  
Angela Rose Brannon ◽  
Joel S Parker ◽  
Jennifer C Fisher ◽  
...  

4522 Background: The objective of this study is to create a molecular tool that can be applied widely to clinical specimens using existing transcript signatures for use in clinical risk prediction of clear cell Renal Cell Carcinoma (ccRCC) to improve personalized disease management. Methods: We developed a 34-gene subtype predictor to classify clear cell tumors according to two subtypes, clear cell A (ccA) or B (ccB). The training set consisted of 72 ccRCC microarray-analyzed tumor samples that had previously been classified by unsupervised clustering and logical analysis of data (LAD). The predictor was developed from a panel of genes significantly expressed in ccA and ccB tumors and associated with prognosis. The prognostic value of the algorithm was corroborated in RNA-sequencing data from 379 ccRCC samples from The Cancer Genome Atlas (TCGA) and further validated using the NanoString platform with a cohort of 163 archival fixed samples collected at the University of North Carolina. Results: Risk associated molecular subtypes, ccA and ccB, were classified in TCGA and NanoString cohorts. Subtype classification showed significant prognostic outcomes for overall survival (p<.001), cancer-specific survival (p=.003), and recurrence-free survival (p<.05) and remained significant in multivariate analyses that included age at diagnosis, gender, ethnicity, pathologic stage, and histologic grade. A prognostic model was built for overall and recurrence-free survival for non-metastatic ccRCC patients within the context of subtype and clinical characteristics. Conclusions: The ccA and ccB subtypes significantly added prognostic information to clinical parameters, particularly for non-metastatic ccRCC patients.The subtypes can be used for future analyses involving risk for developing metastatic disease and cancer-specific outcomes. This research was supported with a grant from the American Association for Cancer Research, and the UNC Lineberger Comprehensive Cancer Center Cancer Cell Biology Training Grant.


2009 ◽  
Vol 27 (28) ◽  
pp. 4709-4717 ◽  
Author(s):  
Hanne Krogh Jensen ◽  
Frede Donskov ◽  
Niels Marcussen ◽  
Marianne Nordsmark ◽  
Finn Lundbeck ◽  
...  

Purpose We have previously demonstrated a significant negative impact of intratumoral neutrophils in metastatic renal cell carcinoma. This study assessed intratumoral neutrophils in localized clear cell renal cell carcinoma (RCC). Patients and Methods The study comprised 121 consecutive patients who had a nephrectomy for localized RCC. Biomarkers (intratumoral CD8+, CD57+ immune cells, CD66b+ neutrophils, and carbonic anhydrase IX [CA IX]) were assessed by immunohistochemistry, and the relationship with clinical and histopathologic features and patient outcome was evaluated. Results The intratumoral neutrophils ranged from zero to 289 cells/mm2 tumor tissue. The presence of intratumoral neutrophils was statistically significantly associated with increasing tumor size, low hemoglobin, high creatinine, and CA IX ≤ 85%. In multivariate analysis, the presence of intratumoral neutrophils (hazard ratio [HR], 3.0; 95% CI, 1.7 to 5.4; P < .0001), pT stage T3b/T4 (HR, 2.1; 95% CI, 1.2 to 3.6; P = .007), and low hemoglobin (HR, 1.8; 95% CI, 1.0 to 3.1; P = .03) were independent prognostic factors significantly associated with short recurrence-free survival. The presence of intratumoral neutrophils was also an independent prognostic factor for cancer-specific survival (HR, 3.5; 95% CI, 1.9 to 6.4; P < .0001) and overall survival (HR, 3.1; 95% CI, 1.9 to 5.0; P < .0001). Applying the prognostic value of intratumoral neutrophils to the Leibovich low-/intermediate-risk group (n = 78) showed a 5-year recurrence-free survival of 53% (95% CI, 34.6% to 71.8%; presence of intratumoral neutrophils) versus 87% (95% CI, 77.8% to 96.8%; absence of intratumoral neutrophils). The estimated concordance index was 0.74 using the Leibovich risk score and 0.80 when intratumoral neutrophils were added. Conclusion The presence of intratumoral neutrophils is a new, strong, independent prognostic factor for short recurrence-free, cancer-specific, and overall survival in localized clear cell RCC.


2019 ◽  
Vol 10 (2) ◽  
pp. 101-111 ◽  
Author(s):  
Sasanka Kumar Barua ◽  
Yashasvi Singh ◽  
Saumar Jyoti Baruah ◽  
Rajeev T.P. ◽  
Puskal K. Bagchi ◽  
...  

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Jun Wang ◽  
Jianhui Chen ◽  
Liren Jiang ◽  
Qi Wu ◽  
Dawei Wang

Purpose. Grade-dependent decrease of lipid storage in clear cell renal cell carcinoma (ccRCC) leads to morphology changes in HE sections. This study investigated the role of cytoplasmic features in frozen sections of ccRCC on prognosis using the digital pathology approach. Methods. We established an automatic pipeline that performed tumor region selection, stain vector normalization, nuclei segmentation, and feature extraction based on the pathologic data from Shanghai General Hospital and The Cancer Genome Atlas database. Extracted features were subjected to survival analysis. Results. Kurtosis of the cytoplasm in the hematoxylin channel was correlated with progression-free survival (HR 0.10, 95% CI: 0.04–0.24, p = 6.52 ∗ 10 − 7 ) and overall survival (HR 0.11, 95% CI: 0.05–0.31, p = 1.72 ∗ 10 − 5 ) in ccRCC, which outperformed other texture features in this analysis. Multivariate Cox regression analysis revealed that low kurtosis of cytoplasm in the hematoxylin channel was an independent predictor for a shorter progression-free survival time ( p = 0.044 ) and overall survival time (p = 0.01). Kaplan–Meier survival analysis of progression-free survival and overall survival also showed a significantly worse prognosis in patients with low kurtosis of the cytoplasm in the hematoxylin channel (both p < 0.0001 ). Lower kurtosis of cytoplasm in the hematoxylin channel was associated with higher pathologic grade, less cholesterol ester, and more mitochondrial DNA content. Conclusion. Kurtosis of the cytoplasm in the hematoxylin channel predicts survival in clear cell renal cell carcinoma.


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