Gene expression analysis of renal carcinoma: adipose differentiation-related protein as a potential diagnostic and prognostic biomarker for clear-cell renal carcinoma

e17078 Background: The Cancer Genome Atlas project has become a leading source for data that has allowed the identification of a broad range of human cancer tumor types and subtypes and has revealed deep complexity with respect to the differentiation, or lack thereof, among human cancers. In particular, differential gene expression analyses have revealed a wealth of active oncogenic pathways, underlying gene mutation drivers, discriminative markers, and candidate therapeutic targets. Despite its rich composition, several factors have led to it not attaining the utility it would seem to offer. Methods: To study this, we dissected molecular subtypes in the TCGA and used the Pan-Kidney (n = 1022 samples) Portion within it to determine where obstacles seem to limit its utility. We re-clustered the renal carcinomas to create more appropriate histology annotations for these samples. The molecular subtypes were then found through K-means using differentially expressed known developmental regulators per histological annotation. After deriving these new annotations, the histology and molecular subtypes were compared to one another via T-test to generate gene modules that characterize these classes/subclasses. Results: We identified a number of factors that include inconsistent metadata attributes, apparent misclassification of histological subtypes, and molecular subtypes that do not match with that obtained by focused approaches to rederive principle subclasses. Our gene modules showed a molecular subtype of clear cell renal carcinoma that was enriched for vascular development and nephron development. In general, the clear cell renal carcinoma and papillary renal cell carcinoma cohorts both showed significant co-expression with atlases that were enriched for genes involved in kidney development. Conclusions: Our atlas highlights the limitations of the current TCGA atlas and provides another tool to capture the rich insights from the TCGA repository through the efforts explained above, highlighted by its use in kidney carcinoma.

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PANK1 is a Prognostic Biomarker Associated with Immune Infiltration of Clear Cell Renal Carcinoma

10.21203/rs.3.rs-957747/v1 ◽

2021 ◽

Author(s):

Baishun Ma ◽

Pu Wang

Keyword(s):

Roc Curve ◽

Renal Carcinoma ◽

Clear Cell ◽

Prognostic Biomarker ◽

Gene Set Enrichment Analysis ◽

Coagulation Cascade ◽

Clear Cell Renal Carcinoma ◽

Immune Infiltration ◽

Cell Renal Carcinoma ◽

The Relationship

Abstract Background: PANK1 is expressed in some cancer types, but its role in clear cell renal carcinoma (ccRCC) is unclear. We aimed to demonstrate the relationship between PANK1 and ccRCC based on a cancer genomic atlas (TCGA) database.Methods: The Kruskal-Wallis test, Wilcoxon signed rank test and logistic regression were used to analyze the relationship between the clinical pathological characteristics of ccRCC and the expression of PANK1. The ROC curve was used to describe the prognostic value of PANK1 using area under curve (AUC) scores. Kaplan-Meier method and Cox regression analysis were used to evaluate the factors affecting the prognosis of ccRCC. Gene set enrichment analysis (GSEA) and immuno-infiltration analysis were performed to identify a significantly related function of PANK1.Results: PANK1 expression in renal clear cell carcinoma was different from that in stage N (P=1.3E-03),sex (P=5.1E-07),stage M(P=8.3E-04),residual tumor(P<0.001),T stage(T1 vsT4(P=6.5E-03),T1vsT3(P=6.9E-06)), histological grade (G1vsG4(P=3.6E-0.5),G2vsG4(P=2.1E-10),G3vsG4(P=1.7E-05)),pathologic stage(STAGE 1vs.STAGE4(P=1.4E-05),STAGE1vs.STAGE3(P=7.1E-05)). The ROC curve suggest that PANK1 has significant diagnostic and prognostic capabilities (AUC =0.898). Low expression of PANK1 predicted poor overall survival (OS) (P<0.001), while that of PANK1 (HR:0.398; 95% CI:0.248-0.639； P<0.001) is OS-independent predictor in patients with ccRCC. GSEA and immune infiltration analysis showed that the expression of PANK1 is related to extracellular matrix receptor pathway, signaling pathway related to hypertrophic cardiomyopathy, cytokine-cytokine receptor interaction pathway, as well as complement and coagulation cascade pathway.Conclusion: PANK1 expression is significantly associated with poor survival and immune infiltration of ccRCC, which may be a promising prognostic biomarker for ccRCC.

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