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2024中国肿瘤标志物学术大会暨CACA整合肿瘤学高峰论坛暨第十七届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会

作者：阮浩宇江苏省人民医院(南京医科大学第一附属医院)

Background: The diagnosis of lung adenocarcinoma(LUAD) leptomeningeal metastasis(LM)remains a clinical challenge. Human epididymis protein 4(HE4) functions as a novel tumor biomarker for cancers. This study aimed to assess the diagnostic value of cerebrospinal fluid(CSF)HE4, and combined with CEACAM6, for LUAD ***: The CSF HE4 protein level was measured in two independent cohorts by electrochemiluminescence. Test cohort included 58 LUAD LM patients, 22 LUAD patients without LM(Wiot-LM), and 68 normal controls. Validation cohort enrolled 50 LUAD LM patients and 40 normal controls, in parallel with Wiot-LM patients without brain metastases(19Wiot-LM/BrM patients) or with Br M(26 Br M patients). The CSF level of CEA, CA125, CA153,CA199, CA724, NSE and ProGRP of these samples was measured by electrochemiluminescence,whereas the CSF CEACAM6 level was detected by enzyme-linked immunosorbent assay(ELISA).In addition, the serum level of these biomarkers was detected by same method as ***: The level of HE4 or CEACAM6 in CSF samples from LUAD LM patients was significantly higher than those from normal controls and Wiot-LM patients. The HE4 level in CSF was higher than that in serum of LM patient. The CSF HE4 or CEACAM6 level for distinguished LM from Wiot-LM showed good performance by receiver-operating characteristic analysis. The better discriminative power for LM was achieved when HE4 was combined with CEACAM6. In addition, the CSF HE4 and CEACAM6 level showed little or no difference between Wiot-LM/BrM and Br M patients, the Br M would not significantly influence the HE4 or CEACAM6 level in CSF. The diagnostic power of CSF CA125, CA153, CA199, CA724, NSE and ProGRP for LUAD LM were not ***: The combination with HE4 and CEACAM6 has the promising application for the diagnosis of LUAD LM.

关键词： cerebrospinal fluid human epididymis protein 4 CEACAM6 lung adenocarcinoma leptomeningeal metastasis

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Unusual magnetic resonance imaging findings of brain and leptomeningeal metastasis in lung adenocarcinoma:A case report

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World Journal of Clinical Cases 2022年第5期10卷 1723-1728页

作者： Na Li Yu-Jun Wang Fang-Mei Zhu Shui-Tang Deng Department of Radiology Tongde Hospital of Zhejiang ProvinceHangzhou 310012Zhejiang ProvinceChina Department of Radiology Zhejiang Provincial Hospital of Chinese MedicineHangzhou 310012Zhejiang ProvinceChina

BACKGROUND Metastatic tumors are the most common malignancies of central nervous system in adults,and the frequent primary lesion is lung *** and leptomeningeal metastases are more common in patients with non-small-cell lung cancer harboring epidermal growth factor receptor ***,the coexist of brain metastasis with leptomeningeal metastasis(LM)in isolated gyriform appearance is *** SUMMARY We herein presented a case of a 76-year-old male with an established diagnosis as lung adenocarcinoma with gyriform-appeared cerebral parenchymal and leptomeningeal metastases,accompanied by mild peripheral edema and avid contrast enhancement on magnetic resonance *** and pathological examinations confirmed the brain and leptomeningeal metastatic lesions in the left frontal cortex,subcortical white matter and local *** This case was unique with respect to the imaging findings of focal gyriform appearance,which might be caused by secondary parenchymal brain metastatic tumors invading into the leptomeninges or coexistence with *** should be aware of this uncommon imaging presentation of tumor metastases to the central nervous system.

关键词： Brain metastasis leptomeningeal metastasis Magnetic resonance imaging Lung cancer Epidermal growth factor receptor Case report

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Activity and bioavailability of tepotinib for leptomeningeal metastasis of NSCLC with MET exon 14 skipping mutation

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Cancer Communications 2021年第1期41卷 83-87页

作者： Hisashi Tanaka Kageaki Taima Tomonori Makiguchi Junichi Nakagawa Takenori Niioka Sadatomo Tasaka Department of Respiratory Medicine Hirosaki University Graduate School of MedicineAomori 036-8562Japan Department of Pharmacy Hirosaki University HospitalAomori 036-8562Japan

Tepotinib is a key drug for cancer patients with mesenchymal-epithelial transition receptor tyrosine kinase proto-oncogene(MET)exon 14 skipping ***,its bioavailability in the cerebrospinal fluid(CSF)in humans has not been fully ***,information about the efficacy of tepotinib in patients with leptomeningeal metastasis is ***,we present the case of a 56-year-old man who was diagnosed with lung adenocarcinoma with MET exon 14 skipping *** was urgently hospitalized due to leptomeningeal *** administered tepotinib 500 mg/day as the second-line therapy and observed improvement in leptomeningeal metastasis and performance *** tepotinib concentrations reached 1,648 ng/mL in the plasma and 30.6 ng/mL in the CSF,with a penetration rate(CSF/plasma)of 1.83%.These demonstrate tepotinib could achieve a high rate of central nervous system transition and could be effective against leptomeningeal metastasis.

关键词： cerebrospinal fluid IC50 leptomeningeal metastasis MET exon 14 skipping mutation non-small cell lung carcinoma performance status pharmacokinetics tepotinib

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Identification of cerebrospinal fluid biomarkers in leptomeningeal metastasis

Identification of cerebrospinal fluid biomarkers in leptomen...

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2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青...

作者：迟喻丹复旦大学脑科学转化研究院

Research Aim: leptomeningeal metastasis（LM） or spread of cancer cells into the cerebrospinal fluid（CSF） presents an opportunity to study dynamic cancer cell-microenvironmental interactions in human disease. Cancer cells within the CSF disseminate throughout the nervous system, along with the infinitely dense tangle of billions of immune cell infiltrations and connections, leading to hot tumor signs in LM. The source of potential molecular biomarkers in CSF remains poorly understood. Making use of our instutution wealth of patient samples and our laboratory mouse models of LM, I proposed to analyze the release of putative biomarkers into the systemic circulation, and compare CSF-derived biomarkers with those in peripheral blood and other sources to identify key molecular players and therefore effective diagnostics and therapeutic approaches in ***: My proposed study has three main significant points: First, we provided direct evidence that proinflammatory cytokines and innate immunity proteins contributes to CSF inflammatory ***, I exploited single-cell RNA sequencing（scRNA-seq） technology, to systematically illustrate the dynamic inflammatory signaling between cancer cells and immune cells both in human disease and in mouse models. Third, the research uncovered the more concentrated proteins in this compartment,the cancer-derived innate immunity proteins served as important biomarkers in CSF within LM, which can be regulated by macrophages-derived proinflammatory ***: This will shed light on the roles of CSF biomarkers and their effects on the development of ***: Together, these results will provide molecular insights into the microenvironmental biomarkers of leptomeningeal metastasis due to the fast accumulation of the secreted proteins by cancer cells and immune cells suggesting novel clinical diagnosis and pharmacologic targets to treat cancer cells within the leptomeningeal space.

关键词： biomarkers cerebrospinal fluid leptomeningeal metastasis inflammation tumor microenvironment

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