Identification of Cerebrospinal Fluid MicroRNAs Associated With Leptomeningeal Metastasis From Lung Adenocarcinoma

Pan, Zhenyu; Yang, Guozi; He, Hua; Gao, Pan; Jiang, Ting; Chen, Yong; Zhao, Gang

doi:10.3389/fonc.2020.00387

Cited by 16 publications

(12 citation statements)

References 35 publications

(37 reference statements)

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“…Moreover, miRNAs are more stable than mRNAs, and thus less prone to external contamination during sample processing, especially in body fluid tests, which showed great prognostic potential in clinical practice. Pan et al[ 26 ] revealed that miR-7641, as a cerebrospinal fluid miRNA, has potential value for diagnosing and monitoring leptomeningeal metastasis. These characteristics make them excellent candidates as circulating biomarkers.…”

Section: Discussionmentioning

confidence: 99%

Cancer-derived exosomal miR-7641 promotes breast cancer progression and metastasis

et al. 2021

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Background Intercellular communication is crucial for breast cancer progression and metastasis. However, the role of cancer-derived exosomes and their crucial microRNA (miRNA) cargoes mediating intercellular communication requires further investigation. Methods Cancer-derived exosomes were isolated using differential centrifugation and differentially expressed miRNAs were determined by microarrays and qRT-PCR analysis. Cell proliferation, wound-healing, Transwell invasion, and tumor xenograft assays were used for functional research. Plasma exosomal RNA was isolated to verify its role as a prognostic biomarker. Results We found that the tumor-promoting capacity of the exosomes was positively related to their cells of origin. MiR-7641 was identified to be the most differentially expressed miRNA, both at endogenous and secretory levels in high-metastatic cancer cells. MiR-7641 could promote tumor cell progression and metastasis, and that these functions of miR-7641 could alter recipient cells via transportation of exosomes. Additionally, exosomal miR-7641 could promote tumor growth in vivo; and its levels were significantly elevated in the plasma of patients with distant metastasis. Bioinformatics analysis has suggested that miR-7641 is correlated with breast cancer survival, and several important cellular and biological processes are closely targeted by miR-7641. Conclusion The findings indicate miR-7641 to be an important component of the cancer exosomes in promoting tumor progression and metastasis via intercellular communication. Additionally, exosomal miR-7641 may serve as a promising non-invasive diagnostic biomarker and potential targetable candidate in breast cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Cancer-derived exosomal miR-7641 promotes breast cancer progression and metastasis

et al. 2021

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“…Others have applied rare cell capture technologies to standard CSF cytology approaches to improve the detection sensitivity of tumor cells [ 56 , 57 , 58 , 59 ]. Approaches examining the genome, transcriptome, proteome, or miRNAs found in CSF may also hold future promise in diagnosing LM [ 37 , 60 , 61 , 62 ]. While these liquid biopsy technologies from CSF are promising in their potential to improve the diagnosis of LM, they have not yet been adopted in diagnostic guidelines or achieved widespread implementation in clinical practice.…”

Section: Diagnosis Of Lmmentioning

confidence: 99%

The Underlying Biology and Therapeutic Vulnerabilities of Leptomeningeal Metastases in Adult Solid Cancers

Dankner

Lam

Degenhard

et al. 2021

Cancers

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Metastasis to the central nervous system occurs in approximately 20% of patients with advanced solid cancers such as lung cancer, breast cancer, and melanoma. While central nervous system metastases most commonly form in the brain parenchyma, metastatic cancer cells may also reside in the subarachnoid space surrounding the brain and spinal cord to form tumors called leptomeningeal metastases. Leptomeningeal metastasis involves cancer cells that reach the subarachnoid space and proliferate in the cerebrospinal fluid compartment within the leptomeninges, a sequela associated with a myriad of symptoms and poor prognosis. Cancer cells exposed to cerebrospinal fluid in the leptomeninges must contend with a unique microenvironment from those that establish within the brain or other organs. Leptomeningeal lesions provide a formidable clinical challenge due to their often-diffuse infiltration within the subarachnoid space. The molecular mechanisms that promote the establishment of leptomeningeal metastases have begun to be elucidated, demonstrating that it is a biological entity distinct from parenchymal brain metastases and is associated with specific molecular drivers. In this review, we outline the current state of knowledge pertaining to the diagnosis, treatment, and molecular underpinnings of leptomeningeal metastasis.

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“…Half of the reported brain miRNAs were found in CSF exosomal fractions, and some miRNAs specifically expressed in brain tissues were detected in CSF but not in serum. Some clinical studies with a lack of controlled comparisons with serum miRNAs reported that cancer progression was associated with levels of certain onco-miRNAs in BM and LM samples [ 9 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies show that relatively low concentrations and small numbers of detectable extracellular miRNAs could be isolated from the CSF [ 19 , 20 , 21 ]. Other studies reported that CSF extracellular miRNAs are differently expressed in CNS diseases [ 22 , 23 , 24 ]. However, it is hard to confirm certain extracellular miRNAs in CSF as biomarkers for LM, and to correlate miRNA profiles with supportive multi-omics data such as CSF proteomics.…”

Section: Introductionmentioning

confidence: 99%

Exploratory Profiling of Extracellular MicroRNAs in Cerebrospinal Fluid Comparing Leptomeningeal Metastasis with Other Central Nervous System Tumor Statuses

Kim

Lee

et al. 2021

JCM

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The diagnosis of leptomeningeal metastasis (LM) is often difficult due to the paucity of cancer cells in cerebrospinal fluid (CSF) and nonspecific findings on neuroimaging. Investigations of extracellular microRNAs (miRNAs) in CSF could be used for both the diagnosis and study of LM pathogenesis because they reflect the activity of disseminating cancer cells. We isolated CSF extracellular miRNAs from patients (n = 65) of different central nervous system tumor statuses, including cancer control, healthy control, LM, brain metastasis (BM), and primary brain tumor (BT) groups, and performed miRNA microarrays. In unsupervised clustering analyses, all LM and two BM samples showed unique profiles. Among 30 miRNAs identified for LM-specific biomarkers via a Prediction Analysis of Microarrays, miR-335-5p and miR-34b-3p were confirmed in both the discovery and validation samples (n = 23). Next, we performed a significance analysis of the microarray (SAM) to extract discriminative miRNA profiles of two selected CSF groups, with LM samples revealing a greater number of discriminative miRNAs than BM and BT samples compared to controls. Using SAM comparisons between LM and BM samples, we identified 30 upregulated and 6 downregulated LM miRNAs. To reduce bias from different primary cancers, we performed a subset analysis with primary non-small cell lung cancer, and 12 of 13 upregulated miRNAs in LM vs. BM belonged to the upregulated miRNAs in LM. We identified possible target genes and their biological processes that could be affected by LM discriminative miRNAs in NSCLC using the gene ontology database. In conclusion, we identified a unique extracellular miRNA profile in LM CSF that was different from BM, suggesting the use of miRNAs as LM biomarkers in studies of LM pathogenesis.

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Identification of Cerebrospinal Fluid MicroRNAs Associated With Leptomeningeal Metastasis From Lung Adenocarcinoma

Cited by 16 publications

References 35 publications

Cancer-derived exosomal miR-7641 promotes breast cancer progression and metastasis

Cancer-derived exosomal miR-7641 promotes breast cancer progression and metastasis

The Underlying Biology and Therapeutic Vulnerabilities of Leptomeningeal Metastases in Adult Solid Cancers

Exploratory Profiling of Extracellular MicroRNAs in Cerebrospinal Fluid Comparing Leptomeningeal Metastasis with Other Central Nervous System Tumor Statuses

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