Cerebrospinal fluid circulating tumour 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/10.1007/s11060-023-04471-8
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1007/s11060-023-04471-8
Purpose The prognosis of patients with leptomeningeal metastasis (LM) remains poor. Circulating tumour DNA (ctDNA) has been proven to be abundantly present in cerebrospinal fluid (CSF); hence, its clinical implication as a biomarker needs to be further verified. Methods We conducted a retrospective study of 35 lung adenocarcinoma (LUAD) patients with LM, and matched CSF and plasma samples were collected from all patients. All paired samples underwent next-generation sequencing (NGS) of 139 lung cancer-associated genes. The clinical characteristics and genetic profiling of LM were analysed in association with survival prognosis. Results LM showed genetic heterogeneity, in which CSF had a higher detection rate of ctDNA ( P = 0.003), a higher median mutation count ( P < 0.0001), a higher frequency of driver mutations ( P < 0.01), and more copy number variation (CNV) alterations ( P < 0.001) than plasma. The mutation frequencies of the EGFR, TP53, CDKN2A, MYC and CDKN2B genes were easier to detect in CSF than in LUAD tissue ( P < 0.05), possibly reflecting the underlying mechanism of LM metastasis. CSF ctDNA is helpful for analysing the mechanism of EGFR-TKI resistance. In cohort 1, which comprised patients who received 1/2 EGFR-TKIs before the diagnosis of LM, TP53 and CDKN2A were the most common EGFR -independent resistant mutations. In cohort 2, comprising those 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 -mutated LUAD ( P = 0.042) had a higher median OS, and CSF ctDNA mutation with TERT ( P = 0.013) indicated a lower median OS. Last, we reported an LM case in which CSF ctDNA dynamic changes were well correlated with clinical treatment. Conclusions CSF ctDNA could provide a more comprehensive genetic landscape of LM, indicating the potential metastasis-related and EGFR-TKI resistance mechanisms of LM patients. In addition, genotyping of CSF combined with clinical outcomes can predict the prognosis of LUAD patients with LM.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1007/s11060-023-04471-8
- https://link.springer.com/content/pdf/10.1007/s11060-023-04471-8.pdf
- OA Status
- hybrid
- Cited By
- 9
- References
- 51
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4388001610
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4388001610Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1007/s11060-023-04471-8Digital Object Identifier
- Title
-
Cerebrospinal fluid circulating tumour DNA genotyping and survival analysis in lung adenocarcinoma with leptomeningeal metastasesWork title
- Type
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articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-10-01Full 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
-
https://doi.org/10.1007/s11060-023-04471-8Publisher landing page
- PDF URL
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https://link.springer.com/content/pdf/10.1007/s11060-023-04471-8.pdfDirect link to full text PDF
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YesWhether a free full text is available
- OA status
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hybridOpen access status per OpenAlex
- OA URL
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https://link.springer.com/content/pdf/10.1007/s11060-023-04471-8.pdfDirect OA link when available
- Concepts
-
Genotyping, Cerebrospinal fluid, Medicine, Adenocarcinoma, Lung cancer, Pathology, Lung, Oncology, Cancer, Internal medicine, Biology, Genotype, Gene, BiochemistryTop concepts (fields/topics) attached by OpenAlex
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9Total citation count in OpenAlex
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2025: 5, 2024: 4Per-year citation counts (last 5 years)
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51Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.The | 2, 76, 142 |
| abstract_inverted_index.all | 62 |
| abstract_inverted_index.and | 53, 56, 79, 129, 151, 203, 222, 240, 263, 312 |
| abstract_inverted_index.but | 234 |
| abstract_inverted_index.can | 328 |
| abstract_inverted_index.for | 180, 245 |
| abstract_inverted_index.had | 99, 228, 258 |
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| abstract_inverted_index.its | 28 |
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| abstract_inverted_index.who | 193, 218 |
| abstract_inverted_index.< | 117, 127, 138, 166 |
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| abstract_inverted_index.EGFR | 209, 229, 251 |
| abstract_inverted_index.LUAD | 162, 253, 333 |
| abstract_inverted_index.TERT | 268 |
| abstract_inverted_index.TP53 | 202 |
| abstract_inverted_index.been | 17 |
| abstract_inverted_index.case | 283 |
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| abstract_inverted_index.from | 61 |
| abstract_inverted_index.lung | 47, 73 |
| abstract_inverted_index.more | 130, 302 |
| abstract_inverted_index.most | 207 |
| abstract_inverted_index.rate | 103 |
| abstract_inverted_index.than | 140, 160 |
| abstract_inverted_index.well | 291 |
| abstract_inverted_index.were | 59, 84, 154, 205, 243, 290 |
| abstract_inverted_index.with | 6, 51, 88, 250, 267, 293, 325, 335 |
| abstract_inverted_index.(CNV) | 134 |
| abstract_inverted_index.(NGS) | 70 |
| abstract_inverted_index.EGFR, | 147 |
| abstract_inverted_index.Last, | 278 |
| abstract_inverted_index.TP53, | 148 |
| abstract_inverted_index.after | 220 |
| abstract_inverted_index.could | 299 |
| abstract_inverted_index.count | 114 |
| abstract_inverted_index.ctDNA | 105, 177, 265, 287, 298 |
| abstract_inverted_index.fluid | 25 |
| abstract_inverted_index.genes | 153, 242 |
| abstract_inverted_index.lower | 275 |
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| abstract_inverted_index.poor. | 11 |
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| abstract_inverted_index.those | 217 |
| abstract_inverted_index.which | 97, 190, 285 |
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| abstract_inverted_index.(LUAD) | 49 |
| abstract_inverted_index.0.001) | 139 |
| abstract_inverted_index.0.01), | 128 |
| abstract_inverted_index.0.013) | 272 |
| abstract_inverted_index.0.042) | 257 |
| abstract_inverted_index.0.05), | 167 |
| abstract_inverted_index.CDKN2A | 204 |
| abstract_inverted_index.CDKN2B | 152 |
| abstract_inverted_index.before | 197 |
| abstract_inverted_index.cohort | 188, 214 |
| abstract_inverted_index.common | 208 |
| abstract_inverted_index.detect | 157 |
| abstract_inverted_index.driver | 123 |
| abstract_inverted_index.easier | 155 |
| abstract_inverted_index.genes. | 75 |
| abstract_inverted_index.hence, | 27 |
| abstract_inverted_index.higher | 101, 111, 120, 260 |
| abstract_inverted_index.median | 112, 261, 276 |
| abstract_inverted_index.number | 132 |
| abstract_inverted_index.paired | 65 |
| abstract_inverted_index.plasma | 57 |
| abstract_inverted_index.proven | 18 |
| abstract_inverted_index.showed | 93 |
| abstract_inverted_index.tissue | 163 |
| abstract_inverted_index.tumour | 13 |
| abstract_inverted_index.(ctDNA) | 15 |
| abstract_inverted_index.0.003), | 109 |
| abstract_inverted_index.CDKN2A, | 149 |
| abstract_inverted_index.Methods | 39 |
| abstract_inverted_index.Purpose | 1 |
| abstract_inverted_index.Results | 91 |
| abstract_inverted_index.changes | 289 |
| abstract_inverted_index.dynamic | 288 |
| abstract_inverted_index.further | 37 |
| abstract_inverted_index.genetic | 80, 94, 304 |
| abstract_inverted_index.helpful | 179 |
| abstract_inverted_index.matched | 54 |
| abstract_inverted_index.patient | 238 |
| abstract_inverted_index.plasma. | 141, 236 |
| abstract_inverted_index.predict | 329 |
| abstract_inverted_index.present | 22 |
| abstract_inverted_index.provide | 300 |
| abstract_inverted_index.remains | 10 |
| abstract_inverted_index.samples | 58, 66 |
| abstract_inverted_index.various | 241 |
| abstract_inverted_index.(43.75%) | 227 |
| abstract_inverted_index.-mutated | 252 |
| abstract_inverted_index.0.0001), | 118 |
| abstract_inverted_index.Abstract | 0 |
| abstract_inverted_index.EGFR-TKI | 185, 313 |
| abstract_inverted_index.Patients | 249 |
| abstract_inverted_index.analysed | 85 |
| abstract_inverted_index.clinical | 29, 77, 294, 326 |
| abstract_inverted_index.combined | 324 |
| abstract_inverted_index.detected | 231 |
| abstract_inverted_index.included | 244 |
| abstract_inverted_index.mutation | 113, 143, 266 |
| abstract_inverted_index.outcomes | 327 |
| abstract_inverted_index.patients | 5, 50, 192, 226, 334 |
| abstract_inverted_index.possibly | 168 |
| abstract_inverted_index.received | 194 |
| abstract_inverted_index.reported | 280 |
| abstract_inverted_index.survival | 89, 247 |
| abstract_inverted_index.EGFR-TKIs | 196 |
| abstract_inverted_index.addition, | 320 |
| abstract_inverted_index.analysing | 181 |
| abstract_inverted_index.analysis. | 248 |
| abstract_inverted_index.biomarker | 33 |
| abstract_inverted_index.collected | 60 |
| abstract_inverted_index.comprised | 191 |
| abstract_inverted_index.conducted | 41 |
| abstract_inverted_index.detection | 102 |
| abstract_inverted_index.developed | 223 |
| abstract_inverted_index.diagnosis | 199 |
| abstract_inverted_index.frequency | 121 |
| abstract_inverted_index.indicated | 273 |
| abstract_inverted_index.landscape | 305 |
| abstract_inverted_index.mechanism | 172, 183 |
| abstract_inverted_index.mutations | 124 |
| abstract_inverted_index.patients. | 63, 318 |
| abstract_inverted_index.potential | 310 |
| abstract_inverted_index.profiling | 81 |
| abstract_inverted_index.prognosis | 3, 331 |
| abstract_inverted_index.resistant | 211 |
| abstract_inverted_index.underwent | 67 |
| abstract_inverted_index.variation | 133 |
| abstract_inverted_index.verified. | 38 |
| abstract_inverted_index.abundantly | 21 |
| abstract_inverted_index.comprising | 216 |
| abstract_inverted_index.correlated | 292 |
| abstract_inverted_index.genotyping | 321 |
| abstract_inverted_index.indicating | 308 |
| abstract_inverted_index.mechanisms | 315 |
| abstract_inverted_index.metastasis | 8 |
| abstract_inverted_index.mutations. | 212 |
| abstract_inverted_index.prognosis. | 90 |
| abstract_inverted_index.progressed | 219 |
| abstract_inverted_index.reflecting | 169 |
| abstract_inverted_index.resistance | 314 |
| abstract_inverted_index.sequencing | 69 |
| abstract_inverted_index.treatment. | 295 |
| abstract_inverted_index.underlying | 171 |
| abstract_inverted_index.Circulating | 12 |
| abstract_inverted_index.Conclusions | 296 |
| abstract_inverted_index.alterations | 135 |
| abstract_inverted_index.association | 87 |
| abstract_inverted_index.frequencies | 144 |
| abstract_inverted_index.implication | 30 |
| abstract_inverted_index.interactive | 246 |
| abstract_inverted_index.metastasis. | 175 |
| abstract_inverted_index.osimertinib | 221 |
| abstract_inverted_index.resistance. | 186 |
| abstract_inverted_index.-independent | 210 |
| abstract_inverted_index.Furthermore, | 237 |
| abstract_inverted_index.cerebrospinal | 24 |
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| abstract_inverted_index.retrospective | 43 |
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| abstract_inverted_index.heterogeneity, | 95 |
| abstract_inverted_index.leptomeningeal | 7 |
| abstract_inverted_index.characteristics | 78, 239 |
| abstract_inverted_index.next-generation | 68 |
| abstract_inverted_index.cancer-associated | 74 |
| abstract_inverted_index.metastasis-related | 311 |
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| cited_by_percentile_year.min | 97 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 13 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/1 |
| sustainable_development_goals[0].score | 0.5600000023841858 |
| sustainable_development_goals[0].display_name | No poverty |
| citation_normalized_percentile.value | 0.90112629 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |