scholarly journals Systematic analysis of alternative splicing signature unveils prognostic predictor for kidney renal clear cell carcinoma

2019 ◽  
Vol 234 (12) ◽  
pp. 22753-22764 ◽  
Author(s):  
Jukun Song ◽  
Yong Da Liu ◽  
Jiaming Su ◽  
Dongbo Yuan ◽  
Fa Sun ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Systematic Analysis ◽  
Prognostic Predictor

scholarly journals Systematic Identification of Survival-Associated Alternative Splicing Events in Kidney Renal Clear Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yubin Wei ◽  
Zheng Zhang ◽  
Rui Peng ◽  
Yan Sun ◽  
Luyu Zhang ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Cell Carcinoma ◽  
Cox Regression ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Splicing Factors ◽  
Interactive Network ◽  
Highly Correlated

There is growing evidence that aberrant alternative splicing (AS) is highly correlated with driving tumorigenesis, but its function in kidney renal clear cell carcinoma (KIRC) remains to be discovered. In this study, we obtained the level-3 RNA sequencing and clinical data of KIRC from The Cancer Genome Atlas (TGCA). Combining with the splicing event detail information from TGCA SpliceSeq database, we established the independent prognosis signatures for KIRC with the univariate and multivariate Cox regression analyses. Then, we used the Kaplan-Meier analysis and receiver operating characteristic curves (ROCs) to assess the accuracy of prognosis signatures. We also constructed the regulatory network of splicing factors (SFs) and AS events. Our results showed that a total of 12029 survival-associated AS events of 5761 genes were found in 524 KIRC patients. All types of prognosis signatures displayed a satisfactory ability to reliably predict, especially in exon skip model which the area under curve of ROC was 0.802. Moreover, 18 splicing factors (SFs) highly correlated to AS events were identified. With the construction of the SF-AS interactive network, we found that SF powerfully promotes the occurrence of abnormal AS and may have a profound role in KIRC. Collectively, we screened survival-associated AS events and established prognosis signatures for KIRC, coupling with the SF-AS interactive network, which might provide a key perspective to clarify the potential mechanism of AS in KIRC.

scholarly journals Alternative splicing associated with cancer stemness in kidney renal clear cell carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lixing Xiao ◽  
Guoying Zou ◽  
Rui Cheng ◽  
Pingping Wang ◽  
Kexin Ma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Logistic Regression ◽  
Alternative Splicing ◽  
Prediction Model ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Cancer Stemness ◽  
Alternative Splicing Events

Abstract Backgroud Cancer stemness is associated with metastases in kidney renal clear cell carcinoma (KIRC) and negatively correlates with immune infiltrates. Recent stemness evaluation methods based on the absolute expression have been proposed to reveal the relationship between stemness and cancer. However, we found that existing methods do not perform well in assessing the stemness of KIRC patients, and they overlooked the impact of alternative splicing. Alternative splicing not only progresses during the differentiation of stem cells, but also changes during the acquisition of the stemness features of cancer stem cells. There is an urgent need for a new method to predict KIRC-specific stemness more accurately, so as to provide help in selecting treatment options. Methods The corresponding RNA-Seq data were obtained from the The Cancer Genome Atlas (TCGA) data portal. We also downloaded stem cell RNA sequence data from the Progenitor Cell Biology Consortium (PCBC) Synapse Portal. Independent validation sets with large sample size and common clinic pathological characteristics were obtained from the Gene Expression Omnibus (GEO) database. we constructed a KIRC-specific stemness prediction model using an algorithm called one-class logistic regression based on the expression and alternative splicing data to predict stemness indices of KIRC patients, and the model was externally validated. We identify stemness-associated alternative splicing events (SASEs) by analyzing different alternative splicing event between high- and low- stemness groups. Univariate Cox and multivariable logistic regression analysisw as carried out to detect the prognosis-related SASEs respectively. The area under curve (AUC) of receiver operating characteristic (ROC) was performed to evaluate the predictive values of our model. Results Here, we constructed a KIRC-specific stemness prediction model with an AUC of 0.968,and to provide a user-friendly interface of our model for KIRC stemness analysis, we have developed KIRC Stemness Calculator and Visualization (KSCV), hosted on the Shiny server, can most easily be accessed via web browser and the url https://jiang-lab.shinyapps.io/kscv/. When applied to 605 KIRC patients, our stemness indices had a higher correlation with the gender, smoking history and metastasis of the patients than the previous stemness indices, and revealed intratumor heterogeneity at the stemness level. We identified 77 novel SASEs by dividing patients into high- and low- stemness groups with significantly different outcome and they had significant correlations with expression of 17 experimentally validated splicing factors. Both univariate and multivariate survival analysis demonstrated that SASEs closely correlated with the overall survival of patients. Conclusions Basing on the stemness indices, we found that not only immune infiltration but also alternative splicing events showed significant different at the stemness level. More importantly, we highlight the critical role of these differential alternative splicing events in poor prognosis, and we believe in the potential for their further translation into targets for immunotherapy.

scholarly journals Integrative Genome-wide Analysis of the Determinants of RNA Splicing in Kidney Renal Clear Cell Carcinoma

2014 ◽  
Author(s):  
Kjong-Van Lehmann ◽  
Andre Kahles ◽  
Cyriac Kandoth ◽  
William Lee ◽  
Nikolaus Schultz ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Alternative Splicing Events ◽  
Splicing Patterns

We present a genome-wide analysis of splicing patterns of 282 kidney renal clear cell carcinoma patients in which we integrate data from whole-exome sequencing of tumor and normal samples, RNA-seq and copy number variation. We proposed a scoring mechanism to compare splicing pat- terns in tumor samples to normal samples in order to rank and detect tumor-specific isoforms that have a potential for new biomarkers. We identified a subset of genes that show introns only observable in tumor but not in normal samples, ENCODE and GEUVADIS samples. In order to improve our understanding of the underlying genetic mechanisms of splicing variation we performed a large-scale association analysis to find links between somatic or germline variants with alternative splicing events. We identified 915 cis- and trans-splicing quantitative trait loci (sQTL) associated with changes in splicing patterns. Some of these sQTL have previously been associated with being susceptibility loci for cancer and other diseases. Our analysis also allowed us to identify the function of several COSMIC variants showing significant association with changes in alternative splicing. This demonstrates the potential significance of variants affecting alternative splicing events and yields insights into the mechanisms related to an array of disease phenotypes.

Delayed Pancreatic Metastasis of Renal Clear Cell Carcinoma

2013 ◽  
Vol 13 (2) ◽  
pp. 79-80
Author(s):  
Zane Simtniece ◽  
Gatis Kirsakmens ◽  
Ilze Strumfa ◽  
Andrejs Vanags ◽  
Maris Pavars ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Surgical Treatment ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Primary Tumour ◽  
Renal Clear Cell Carcinoma ◽  
Pancreatic Metastasis ◽  
Distal Pancreatic Resection

Abstract Here, we report surgical treatment of a patient presenting with pancreatic metastasis (MTS) of renal clear cell carcinoma (RCC) 11 years after nephrectomy. RCC is one of few cancers that metastasise in pancreas. Jaundice, abdominal pain or gastrointestinal bleeding can develop; however, asymptomatic MTS can be discovered by follow-up after removal of the primary tumour. The patient, 67-year-old female was radiologically diagnosed with a clinically silent mass in the pancreatic body and underwent distal pancreatic resection. The postoperative period was smooth. Four months after the surgery, there were no signs of disease progression.

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