Cerebrospinal Fluid Circulating Tumor DNA Genotyping and Survival Analysis in Lung Adenocarcinoma With Leptomeningeal Metastases Article Swipe
Kaixuan Bai
,
Xin Chen
,
Xuejiao Qi
,
Yu Zhang
,
Yueli Zou
,
Jian Li
,
Lili Yu
,
Yuanyuan Li
,
Jiajia Jiang
,
Yi Yang
,
Yajing Liu
,
Shuanghao Feng
,
Hui Bu
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-3309843/v1
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-3309843/v1
Purpose The prognosis of patients with leptomeningeal metastasis (LM) remains poor. Circulating tumor DNA (ctDNA) has been proven more abundantly present in the cerebrospinal fluid (CSF), hence, its clinical implication as a biomarker need to be further verified. Methods We conducted a retrospective study of 35 lung adenocarcinoma (LUAD) patients with LM, and all patients collected matched CSF and plasma samples. All paired samples underwent next-generation sequencing (NGS) of 139 lung cancer-associated genes. The clinical characteristics and genetic profiling of LM were analyzed association with survival prognosis. Results LM showed genetic heterogeneity, which CSF had higher detection rate of ctDNA ( P = 0.003), more median mutations count ( P < 0.0001), higher frequencies of driver mutations ( P < 0.01), more copy number variations (CNVs) alterations ( P < 0.001) than plasma. The mutation frequency of EGFR, TP53, CDKN2A, MYC and CDKN2B genes were easier to be detected in CSF than in LUAD tissue ( P < 0.05), this may reveal the underlying mechanism of LM metastasis. CSF ctDNA is helpful to analyze the mechanism of EGFR-TKIs resistance. In cohort 1, who receive 1/2 EGFR-TKIs before the diagnosis of LM, TP53 and CDKN2A were the most common EGFR-independent resistant mutations. In cohort 2, who progressed after osimertinib and developed LM, 7 patients (43.75%) had EGFR CNV detected in CSF but not plasma. Furthermore, patient characteristics and various genes were included for interactive survival analysis. Patients with EGFR gene mutation in lung tissue ( P = 0.042) had higher median OS and CSF ctDNA mutation with TERT ( P = 0.013) indicated lower median OS. Lastly, we reported a LM case whose CSF ctDNA dynamic changes were well correlated with his clinical treatment. Conclusions CSF ctDNA could provide a more comprehensive genetic landscape of LM, which indicated the potential metastasis-related and EGFR-TKIs resistance mechanisms of LM patients. Besides, genotyping of CSF combined with clinical outcomes can predict the prognosis of LUAD patients with LM.
Related Topics
Concepts
CDKN2A
Cerebrospinal fluid
Medicine
Adenocarcinoma
Lung cancer
Genotyping
Liquid biopsy
Oncology
Lung
Brain metastasis
Internal medicine
Pathology
Cancer research
Metastasis
Cancer
Genotype
Gene
Biology
Biochemistry
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-3309843/v1
- https://www.researchsquare.com/article/rs-3309843/latest.pdf
- OA Status
- green
- References
- 49
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4386457317
All OpenAlex metadata
Raw OpenAlex JSON
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https://openalex.org/W4386457317Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.21203/rs.3.rs-3309843/v1Digital Object Identifier
- Title
-
Cerebrospinal Fluid Circulating Tumor DNA Genotyping and Survival Analysis in Lung Adenocarcinoma With Leptomeningeal MetastasesWork title
- Type
-
preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-09-05Full publication date if available
- Authors
-
Kaixuan Bai, Xin Chen, Xuejiao Qi, Yu Zhang, Yueli Zou, Jian Li, Lili Yu, Yuanyuan Li, Jiajia Jiang, Yi Yang, Yajing Liu, Shuanghao Feng, Hui BuList of authors in order
- Landing page
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https://doi.org/10.21203/rs.3.rs-3309843/v1Publisher landing page
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https://www.researchsquare.com/article/rs-3309843/latest.pdfDirect link to full text PDF
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.researchsquare.com/article/rs-3309843/latest.pdfDirect OA link when available
- Concepts
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CDKN2A, Cerebrospinal fluid, Medicine, Adenocarcinoma, Lung cancer, Genotyping, Liquid biopsy, Oncology, Lung, Brain metastasis, Internal medicine, Pathology, Cancer research, Metastasis, Cancer, Genotype, Gene, Biology, BiochemistryTop concepts (fields/topics) attached by OpenAlex
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0Total citation count in OpenAlex
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.remains | 10 |
| abstract_inverted_index.samples | 64 |
| abstract_inverted_index.various | 228 |
| abstract_inverted_index.(43.75%) | 214 |
| abstract_inverted_index.0.0001), | 112 |
| abstract_inverted_index.Abstract | 0 |
| abstract_inverted_index.Besides, | 308 |
| abstract_inverted_index.Patients | 236 |
| abstract_inverted_index.analyzed | 83 |
| abstract_inverted_index.clinical | 29, 75, 282, 314 |
| abstract_inverted_index.combined | 312 |
| abstract_inverted_index.detected | 149, 218 |
| abstract_inverted_index.included | 231 |
| abstract_inverted_index.mutation | 135, 240, 255 |
| abstract_inverted_index.outcomes | 315 |
| abstract_inverted_index.patients | 5, 50, 55, 213, 322 |
| abstract_inverted_index.reported | 268 |
| abstract_inverted_index.samples. | 61 |
| abstract_inverted_index.survival | 86, 234 |
| abstract_inverted_index.EGFR-TKIs | 178, 186, 302 |
| abstract_inverted_index.analysis. | 235 |
| abstract_inverted_index.biomarker | 33 |
| abstract_inverted_index.collected | 56 |
| abstract_inverted_index.conducted | 41 |
| abstract_inverted_index.detection | 97 |
| abstract_inverted_index.developed | 210 |
| abstract_inverted_index.diagnosis | 189 |
| abstract_inverted_index.frequency | 136 |
| abstract_inverted_index.indicated | 262, 297 |
| abstract_inverted_index.landscape | 293 |
| abstract_inverted_index.mechanism | 165, 176 |
| abstract_inverted_index.mutations | 107, 117 |
| abstract_inverted_index.patients. | 307 |
| abstract_inverted_index.potential | 299 |
| abstract_inverted_index.profiling | 79 |
| abstract_inverted_index.prognosis | 3, 319 |
| abstract_inverted_index.resistant | 200 |
| abstract_inverted_index.underwent | 65 |
| abstract_inverted_index.verified. | 38 |
| abstract_inverted_index.abundantly | 20 |
| abstract_inverted_index.correlated | 279 |
| abstract_inverted_index.genotyping | 309 |
| abstract_inverted_index.mechanisms | 304 |
| abstract_inverted_index.metastasis | 8 |
| abstract_inverted_index.mutations. | 201 |
| abstract_inverted_index.prognosis. | 87 |
| abstract_inverted_index.progressed | 206 |
| abstract_inverted_index.resistance | 303 |
| abstract_inverted_index.sequencing | 67 |
| abstract_inverted_index.treatment. | 283 |
| abstract_inverted_index.underlying | 164 |
| abstract_inverted_index.variations | 125 |
| abstract_inverted_index.Circulating | 12 |
| abstract_inverted_index.Conclusions | 284 |
| abstract_inverted_index.alterations | 127 |
| abstract_inverted_index.association | 84 |
| abstract_inverted_index.frequencies | 114 |
| abstract_inverted_index.implication | 30 |
| abstract_inverted_index.interactive | 233 |
| abstract_inverted_index.metastasis. | 168 |
| abstract_inverted_index.osimertinib | 208 |
| abstract_inverted_index.resistance. | 179 |
| abstract_inverted_index.Furthermore, | 224 |
| abstract_inverted_index.cerebrospinal | 24 |
| abstract_inverted_index.comprehensive | 291 |
| abstract_inverted_index.retrospective | 43 |
| abstract_inverted_index.adenocarcinoma | 48 |
| abstract_inverted_index.heterogeneity, | 92 |
| abstract_inverted_index.leptomeningeal | 7 |
| abstract_inverted_index.characteristics | 76, 226 |
| abstract_inverted_index.next-generation | 66 |
| abstract_inverted_index.EGFR-independent | 199 |
| abstract_inverted_index.cancer-associated | 72 |
| abstract_inverted_index.metastasis-related | 300 |
| cited_by_percentile_year | |
| countries_distinct_count | 1 |
| institutions_distinct_count | 13 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/1 |
| sustainable_development_goals[0].score | 0.49000000953674316 |
| sustainable_development_goals[0].display_name | No poverty |
| citation_normalized_percentile.value | 0.48021785 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |