Prognostic Molecular Signatures for Metastatic Potential in Clinically Low-Risk Stage I and II Clear Cell Renal Cell Carcinomas Article Swipe
Andrew Shih
,
Neal Murphy
,
Zachary Kozel
,
Paras Shah
,
Oksana Yaskiv
,
Houman Khalili
,
Anthony Liew
,
Louis R. Kavoussi
,
Simon J. Hall
,
Manish Vira
,
Xinhua Zhu
,
Annette T. Lee
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.3389/fonc.2020.01383
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.3389/fonc.2020.01383
Introduction: For patients with localized node-negative (Stage I and II) clear cell renal cell carcinomas (ccRCC), current clinicopathological staging has limited predictive capability because of their low risk. Analyzing molecular signatures at the time of nephrectomy can aid in understanding future metastatic potential. Objective: Develop a molecular signature that can stratify patients who have clinically low risk ccRCC, but have high risk genetic changes driving an aggressive metastatic phenotype. Patients, Materials, and Methods: Presented is the differential expression of mRNA and miRNA in 44 Stage I and Stage II patients, 21 who developed metastasis within 5 years of nephrectomy, compared to 23 patients who remained disease free for more than 5 years. Extracted RNA from nephrectomy specimens preserved in FFPE blocks was sequenced using RNAseq. MiRNA expression was performed using the TaqMan OpenArray qPCR protocol. Results: One hundred thirty one genes and 2 miRNA were differentially expressed between the two groups. Canonical correlation (CC) analysis was applied and four CCs (CC32, CC20, CC9, and CC7) have an AUC > 0.65 in our dataset with similar predictive power in the TCGA-KIRC dataset. Gene set enrichment showed CC9 as kidney development/adhesion, CC20 as oxidative phosphorylation pathway, CC32 as RNA binding/spindle and CC7 as immune response. In a multivariate Cox model, the four CCs were able to identify high/low risk groups for metastases in the TCGA-KIRC (p < 0.05) with odds ratios of CC32 = 5.7, CC20 = 4.4, CC9 = 3.6, and CC7 = 2.7. Conclusion: These results identify molecular signatures for more aggressive tumors in clinically low risk ccRCC patients who have a higher potential of metastasis than would be expected.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fonc.2020.01383
- OA Status
- gold
- Cited By
- 2
- References
- 50
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3040610124
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3040610124Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3389/fonc.2020.01383Digital Object Identifier
- Title
-
Prognostic Molecular Signatures for Metastatic Potential in Clinically Low-Risk Stage I and II Clear Cell Renal Cell CarcinomasWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2020Year of publication
- Publication date
-
2020-08-11Full publication date if available
- Authors
-
Andrew Shih, Neal Murphy, Zachary Kozel, Paras Shah, Oksana Yaskiv, Houman Khalili, Anthony Liew, Louis R. Kavoussi, Simon J. Hall, Manish Vira, Xinhua Zhu, Annette T. LeeList of authors in order
- Landing page
-
https://doi.org/10.3389/fonc.2020.01383Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.3389/fonc.2020.01383Direct OA link when available
- Concepts
-
Nephrectomy, Clear cell renal cell carcinoma, Stage (stratigraphy), Oncology, Renal cell carcinoma, Metastasis, Medicine, Internal medicine, microRNA, Biology, Kidney, Gene, Cancer research, Cancer, Genetics, PaleontologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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2Total citation count in OpenAlex
- Citations by year (recent)
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2023: 1, 2021: 1Per-year citation counts (last 5 years)
- References (count)
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50Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.were | 144, 211 |
| abstract_inverted_index.with | 3, 173, 226 |
| abstract_inverted_index.0.05) | 225 |
| abstract_inverted_index.CC20, | 161 |
| abstract_inverted_index.MiRNA | 125 |
| abstract_inverted_index.Stage | 84, 87 |
| abstract_inverted_index.These | 244 |
| abstract_inverted_index.ccRCC | 257 |
| abstract_inverted_index.clear | 10 |
| abstract_inverted_index.genes | 140 |
| abstract_inverted_index.miRNA | 81, 143 |
| abstract_inverted_index.power | 176 |
| abstract_inverted_index.renal | 12 |
| abstract_inverted_index.risk. | 27 |
| abstract_inverted_index.their | 25 |
| abstract_inverted_index.using | 123, 129 |
| abstract_inverted_index.would | 267 |
| abstract_inverted_index.years | 96 |
| abstract_inverted_index.(CC32, | 160 |
| abstract_inverted_index.(Stage | 6 |
| abstract_inverted_index.TaqMan | 131 |
| abstract_inverted_index.blocks | 120 |
| abstract_inverted_index.ccRCC, | 57 |
| abstract_inverted_index.future | 40 |
| abstract_inverted_index.groups | 217 |
| abstract_inverted_index.higher | 262 |
| abstract_inverted_index.immune | 201 |
| abstract_inverted_index.kidney | 187 |
| abstract_inverted_index.model, | 207 |
| abstract_inverted_index.ratios | 228 |
| abstract_inverted_index.showed | 184 |
| abstract_inverted_index.thirty | 138 |
| abstract_inverted_index.tumors | 252 |
| abstract_inverted_index.within | 94 |
| abstract_inverted_index.years. | 111 |
| abstract_inverted_index.Develop | 44 |
| abstract_inverted_index.RNAseq. | 124 |
| abstract_inverted_index.applied | 156 |
| abstract_inverted_index.because | 23 |
| abstract_inverted_index.between | 147 |
| abstract_inverted_index.changes | 63 |
| abstract_inverted_index.current | 16 |
| abstract_inverted_index.dataset | 172 |
| abstract_inverted_index.disease | 105 |
| abstract_inverted_index.driving | 64 |
| abstract_inverted_index.genetic | 62 |
| abstract_inverted_index.groups. | 150 |
| abstract_inverted_index.hundred | 137 |
| abstract_inverted_index.limited | 20 |
| abstract_inverted_index.results | 245 |
| abstract_inverted_index.similar | 174 |
| abstract_inverted_index.staging | 18 |
| abstract_inverted_index.(ccRCC), | 15 |
| abstract_inverted_index.analysis | 154 |
| abstract_inverted_index.compared | 99 |
| abstract_inverted_index.dataset. | 180 |
| abstract_inverted_index.high/low | 215 |
| abstract_inverted_index.identify | 214, 246 |
| abstract_inverted_index.pathway, | 193 |
| abstract_inverted_index.patients | 2, 51, 102, 258 |
| abstract_inverted_index.remained | 104 |
| abstract_inverted_index.stratify | 50 |
| abstract_inverted_index.(<i>p</i> | 223 |
| abstract_inverted_index.Analyzing | 28 |
| abstract_inverted_index.Canonical | 151 |
| abstract_inverted_index.Extracted | 112 |
| abstract_inverted_index.OpenArray | 132 |
| abstract_inverted_index.Presented | 73 |
| abstract_inverted_index.TCGA-KIRC | 179, 222 |
| abstract_inverted_index.developed | 92 |
| abstract_inverted_index.expected. | 269 |
| abstract_inverted_index.expressed | 146 |
| abstract_inverted_index.localized | 4 |
| abstract_inverted_index.molecular | 29, 46, 247 |
| abstract_inverted_index.oxidative | 191 |
| abstract_inverted_index.patients, | 89 |
| abstract_inverted_index.performed | 128 |
| abstract_inverted_index.potential | 263 |
| abstract_inverted_index.preserved | 117 |
| abstract_inverted_index.protocol. | 134 |
| abstract_inverted_index.response. | 202 |
| abstract_inverted_index.sequenced | 122 |
| abstract_inverted_index.signature | 47 |
| abstract_inverted_index.specimens | 116 |
| abstract_inverted_index.Materials, | 70 |
| abstract_inverted_index.aggressive | 66, 251 |
| abstract_inverted_index.capability | 22 |
| abstract_inverted_index.carcinomas | 14 |
| abstract_inverted_index.clinically | 54, 254 |
| abstract_inverted_index.enrichment | 183 |
| abstract_inverted_index.expression | 77, 126 |
| abstract_inverted_index.metastases | 219 |
| abstract_inverted_index.metastasis | 93, 265 |
| abstract_inverted_index.metastatic | 41, 67 |
| abstract_inverted_index.phenotype. | 68 |
| abstract_inverted_index.potential. | 42 |
| abstract_inverted_index.predictive | 21, 175 |
| abstract_inverted_index.signatures | 30, 248 |
| abstract_inverted_index.correlation | 152 |
| abstract_inverted_index.nephrectomy | 35, 115 |
| abstract_inverted_index.<b>Patients, | 69 |
| abstract_inverted_index.Methods:</b> | 72 |
| abstract_inverted_index.differential | 76 |
| abstract_inverted_index.multivariate | 205 |
| abstract_inverted_index.nephrectomy, | 98 |
| abstract_inverted_index.node-negative | 5 |
| abstract_inverted_index.understanding | 39 |
| abstract_inverted_index.differentially | 145 |
| abstract_inverted_index.<b>Results:</b> | 135 |
| abstract_inverted_index.binding/spindle | 197 |
| abstract_inverted_index.phosphorylation | 192 |
| abstract_inverted_index.<b>Objective:</b> | 43 |
| abstract_inverted_index.<b>Conclusion:</b> | 243 |
| abstract_inverted_index.clinicopathological | 17 |
| abstract_inverted_index.<b>Introduction:</b> | 0 |
| abstract_inverted_index.development/adhesion, | 188 |
| cited_by_percentile_year.max | 94 |
| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5101539456, https://openalex.org/A5041698645 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 12 |
| corresponding_institution_ids | https://openalex.org/I1302444339, https://openalex.org/I1327576362, https://openalex.org/I4210106353 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7699999809265137 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.60513135 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |