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pmid:34133324
Identification of microenvironment related potential biomarkers of biochemical recurrence at 3 years after prostatectomy in prostate adenocarcinoma.
Xiaoru Sun · Lu Wang · Hongkai Li · Chuandi Jin · Yuanyuan Yu · Lei Hou · Xinhui Liu · Yifan Yu · Ran Yan · Fuzhong Xue
Aging · 2021 doi:10.18632/aging.203121
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Identification of multiple causative biomarkers is necessary and helpful for determining the occurrence and prognosis of prostate adenocarcinoma. We aimed to identify the potential prognostic genes in the prostate adenocarcinoma microenvironment and to estimate the causal effects simultaneously. We obtained the gene expression data of prostate adenocarcinoma from TCGA project and identified the differentially expressed genes based on immune-stromal components. Among these genes, 68 were associated with biochemical recurrence at 3 years after prostatectomy in prostate adenocarcinoma. After adjusting for the minimal sets of confounding covariates, 14 genes (TNFRSF4, ZAP70, ERMN, CXCL5, SPINK6, SLC6A18, CHRM2, TG, CLLU1OS, POSTN, CTSG, NETO1, CEACAM7, and IGLV3-22) related to the microenvironment were identified as prognostic biomarkers using the targeted maximum likelihood estimation. Both the average and individual causal effects were obtained to measure the magnitude of the effect. CIBERSORT and gene set enrichment analyses showed that these prognostic genes were mainly associated with immune responses. POSTN and NETO1 were correlated with androgen receptor expression, a main driver of prostate adenocarcinoma progression. Finally, five genes were validated in another prostate adenocarcinoma cohort (GEO: GSE70770). These findings might lead to the improved prognosis of prostate adenocarcinoma.", "claims": [{"id": "claim-method", "statement": "In this study, we used targeted maximum likelihood estimation (TMLE), a doubly robust method to detect the prognostic genes and estimate both the average and individual causal effects [16–18].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34133324", "locator": "sections[1] \"INTRODUCTION\" paragraph 4", "quote": "In this study, we used targeted maximum likelihood estimation (TMLE), a doubly robust method to detect the prognostic genes and estimate both the average and individual causal effects [16–18]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The transcriptome RNA sequence read count data of 550 patients with PRAD and their corresponding clinical profiles were obtained from TCGA (https://portal.gdc.cancer.gov). 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