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ROTS: reproducible RNA-seq biomarker detector-prognostic markers for clear cell renal cell cancer.

ABSTRACT: Recent comprehensive assessments of RNA-seq technology support its utility in quantifying gene expression in various samples. The next step of rigorously quantifying differences between sample groups, however, still lacks well-defined best practices. Although a number of advanced statistical methods have been developed, several studies demonstrate that their performance depends strongly on the data under analysis, which compromises practical utility in real biomedical studies. As a solution, we propose to use a data-adaptive procedure that selects an optimal statistic capable of maximizing reproducibility of detections. After demonstrating its improved sensitivity and specificity in a controlled spike-in study, the utility of the procedure is confirmed in a real biomedical study by identifying prognostic markers for clear cell renal cell carcinoma (ccRCC). In addition to identifying several genes previously associated with ccRCC prognosis, several potential new biomarkers among genes regulating cell growth, metabolism and solute transport were detected.

SUBMITTER: Seyednasrollah F

PROVIDER: S-EPMC4705679 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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ROTS: reproducible RNA-seq biomarker detector-prognostic markers for clear cell renal cell cancer.

Seyednasrollah Fatemeh F Rantanen Krista K Jaakkola Panu P Elo Laura L LL

Nucleic acids research 20150811 1

Recent comprehensive assessments of RNA-seq technology support its utility in quantifying gene expression in various samples. The next step of rigorously quantifying differences between sample groups, however, still lacks well-defined best practices. Although a number of advanced statistical methods have been developed, several studies demonstrate that their performance depends strongly on the data under analysis, which compromises practical utility in real biomedical studies. As a solution, we ...[more]

PMID: 26264667

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Project description:Background: Apolipoprotein C1 (APOC1) has been proved to play a critical role in gastric, breast, lung, and pancreatic cancer. However, the relationship between APOC1 and urinary tumors remains unclear. This study aimed to assess the diagnostic and prognostic value of APOC1 in urinary tumors. Methods: We performed a pan analysis of APOC1 mRNA expression in urinary cancer using the Gene Expression Profiling Interactive Analysis (GEPIA) database. To further investigate the prognostic value of APOC1 expression in urinary cancers, the Kaplan-Meier plotter database was used. Furthermore, we collected the tumor and adjacent normal samples of 32 ccRCC patients to perform qRT-PCR and western blotting assays. A total of 72 cases with ccRCC were analyzed using tissue microarrays (TMAs). Results: Our results based on Kaplan-Meier plotter database indicated that a high expression of APOC1 may lead to poor overall survival (OS, p = 0.0019) in patients with ccRCC. Furthermore, the cancer stages and tumor grade of ccRCC appeared to be strongly linked with APOC1 expression according to UALCAN database. Hence, we reached a preliminary conclusion that APOC1 may play a key role in the tumorigenesis and progression of ccRCC. Furthermore, the Kaplan-Meier survival curve analyses of 72 clinical patients indicated that high expression of APOC1 was associated with poor progression-free survival (PFS, p = 0.007) and OS (p = 0.022). In addition, univariate Cox regression analysis confirmed the significant relationship between APOC1 expression and survival (p = 0.038). The TMAs analysis in combination with the patients' clinicopathological features was also performed. The expression of APOC1 was found to be significantly correlated with the tumor size (p = 0.018) and histological grade (p = 0.016). Conclusions: In conclusion, the findings of our study suggest that APOC1 may serve as a novel diagnostic and prognostic biomarker for ccRCC. Further evidence on the mechanism of APOC1 promoting tumor progression may transform it to a new therapeutic target for the treatment of ccRCC.

Project description:ObjectiveInsulin Growth Factor-Like receptor 1 (IGFLR1) reflects progressive disease and confers a poor prognosis in clear cell renal cell cancer (ccRCC). However, extensive studies highlighting the mechanisms involved in how IGFLR1 triggers the progression of ccRCC remain lacking.MethodsIn the present study, the expression level of IGFLR1 mRNA and correlation between IGFLR1 expression and prognosis of ccRCC were analyzed based on The Cancer Genome Atlas (TCGA) ccRCC cohort. Further, we analyzed methylation and copy number variation to try to explain the difference in IGFLR1 expression. Subsequently, we investigated the correlation between IGFLR1 and tumor-infiltrating immune cells with the aid of TIMER (Tumor Immune Estimation Resource). The potential candidates' genes associated with IGFLR1 were screened by variation analysis, which were used for further enrichment analysis of signaling pathways and immune gene sets to infer the certain function and corresponding mechanisms in which IGFLR1 was involved in ccRCC. Finally, we establish prognostic risk models using multivariate Cox regression analysis and analyzed the possible involvement of IGFLR1 in chemotherapeutic drug resistance.ResultsThe results showed that upregulated IGFLR1 was detected in ccRCC compared with para-cancer tissues and significantly affected the prognosis of ccRCC (overall survival: Logrank p < 0.0001; disease free survival: Logrank p = 0.022). Univariate and multivariate analyses indicated that IGFLR1 was an independent prognostic factor for ccRCC (HR = 2.064, p = 0.006) and the risk prognostic model based on age, M, level of platelet and calcium and IGFLR1 expression had satisfying predictive ability. The correlation analysis showed that the expression level of IGFLR1 was positively correlated with the abundance of myeloid derived suppressor cell and their marker genes in ccRCC significantly. IGFLR1 may be related to the regulatory activation, intercellular adhesion of lymphocytes and drug resistance in cancer.ConclusionThese findings suggested that IGFLR1 was significantly associated with the prognosis in a variety of cancers, particularly ccRCC. IGFLR1 may play an important role in tumor related immune infiltration and showed potential diagnostic, therapeutic and prognostic value in ccRCC.

Dataset Information

ROTS: reproducible RNA-seq biomarker detector-prognostic markers for clear cell renal cell cancer.

Publications

ROTS: reproducible RNA-seq biomarker detector-prognostic markers for clear cell renal cell cancer.

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