Cerebrospinal fluid as a medium of liquid biopsy in the management of patients with non-small-cell lung cancer having central nervous system metastasis

Chiang, Chi‐Lu; Huang, Hui‐Chun; Luo, Yung‐Hung; Chiu, Chao‐Hua

doi:10.52586/5060

Cited by 7 publications

(8 citation statements)

References 71 publications

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“…NSCLC is a malignant lung tumor ( 24 ), and patients with advanced NSCLC have a poor prognosis. In the era of precision cancer therapy, NSCLC treatment includes chemotherapy, immunotherapy, and targeted therapy ( 6 , 25 ). In the existing treatment model, the overall cure rate for NSCLC patients is <20%, and the 5-year survival rate for advanced patients is <5% ( 4 ).…”

Section: Discussionmentioning

confidence: 99%

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Circ_0003028 enhances the proliferation and glycolytic capacity and suppresses apoptosis in non-small cell lung cancer cells via the miR-1305/miR-1322-SLC5A1 axis

Shi¹,

Huang²,

Chen³

et al. 2023

Ann Transl Med

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Background Circular RNA (circRNA), a unique RNA molecule with a circular structure, is relevant to the process of non-small cell lung cancer (NSCLC). However, the role and possible mechanisms of circ_0003028 in NSCLC are not completely clear. Here, we investigated the role of circ_0003028 in NSCLC progression. Methods We first confirmed the stability and head-to-tail junction sequences of circ_000302. Circ_0003028 expression was identified with quantitative reverse transcription polymerase chain reaction (qRT-PCR) in NSCLC tissues, and the survival probability and prognosis were analyzed using Kaplan-Meier survival and receiver operating characteristic (ROC) analyses. Functionally, the proliferation, apoptosis, and glycolytic capacity were examined using cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) staining, a flow cytometer, commercial kits [glucose, lactate, and adenosine triphosphate (ATP)], and a Seahorse XF extracellular flux analyzer. Moreover, the potential microRNAs (miRNAs) of circ_0003028 were predicted and identified, and the target gene of miRNA (miR)-1322 and miR-1305 were also screened using DIANA-microT and TargetScan. Results We first determined the head-to-tail junction sequences of circ_0003028 and its stability. Circ_0003028 was also confirmed to be upregulated in NSCLC tissues. Meanwhile, circ_0003028 had poor overall survival and high diagnostic potential in NSCLC patients. Furthermore, we found that overexpression of circ_0003028 could increase the proliferation and glycolytic capacity and restrain the apoptosis of NSCLC cells, and circ_0003028 silencing played the opposite role to circ_0003028 overexpression. Moreover, circ_0003028 might regulate miR-1305 and miR-1322, which might further regulate solute carrier family 5 member 1 (SLC5A1). Conclusions Circ_0003028 could accelerate the malignant behaviors and glycolytic capacity of NSCLC cells via a mechanism that may be related to miR-1305 or the miR-1322/SLC5A1 axis. Therefore, the findings of the current study provide a preliminary theoretical basis for NSCLC therapy and diagnosis.

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Section: Discussionmentioning

confidence: 99%

“…After surgery, these intermediate and advanced patients may also have local recurrence or general metastasis ( 4 ). In recent years, new therapeutic approaches, such as immunotherapy and targeted therapy, have also increased the 5-year survival rate ( 5 , 6 ). However, these current therapeutic approaches are far from sufficient.…”

Section: Introductionmentioning

confidence: 99%

Circ_0003028 enhances the proliferation and glycolytic capacity and suppresses apoptosis in non-small cell lung cancer cells via the miR-1305/miR-1322-SLC5A1 axis

Shi¹,

Huang²,

Chen³

et al. 2023

Ann Transl Med

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“…A prospective study showed that the supernatant of cerebrospinal fluid (CSF) in patients with EGFR-mutant NSCLC and leptomeningeal metastasis (LM) is a valuable specimen for EGFR mutation testing, demonstrating that the detection rates of EGFR mutations and T790M in cell-free DNA (cfDNA) of CSF were 68.8%, and 14.6%, respectively. [65] The best way to use CSF for diagnosis, tracking tumor heterogeneity, or treatment guidance requires further investigation [66]. CSF diversion, including ventricular peritoneal shunt, and lumbar peritoneal shunt has been reported to be a useful and safe management for LM and hydrocephalus [67].…”

Section: Egfrmentioning

confidence: 99%

State-of-the-Art Molecular Oncology of Lung Cancer in Taiwan

Luo

Liang²,

Huang³

et al. 2022

IJMS

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Lung cancers are life-threatening malignancies that cause great healthcare burdens in Taiwan and worldwide. The 5-year survival rate for Taiwanese patients with lung cancer is approximately 29%, an unsatisfactorily low number that remains to be improved. We first reviewed the molecular epidemiology derived from a deep proteogenomic resource in Taiwan. The nuclear factor erythroid 2-related factor 2 (NRF2)antioxidant mechanism was discovered to mediate the oncogenesis and tumor progression of lung adenocarcinoma. Additionally, DNA replication, glycolysis and stress response are positively associated with tumor stages, while cell-to-cell communication, signaling, integrin, G protein coupled receptors, ion channels and adaptive immunity are negatively associated with tumor stages. Three patient subgroups were discovered based on the clustering analysis of protein abundance in tumors. The first subgroup is associated with more advanced cancer stages and visceral pleural invasion, as well as higher mutation burdens. The second subgroup is associated with EGFR L858R mutations. The third subgroup is associated with PI3K/AKT pathways and cell cycles. Both EGFR and PI3K/AKT signaling pathways have been shown to induce NRF2 activation and tumor cell proliferation. We also reviewed the clinical evidence of patient outcomes in Taiwan given various approved targeted therapies, such as EGFR-tyrosine kinase inhibitors and anaplastic lymphoma kinase (ALK)inhibitors, in accordance with the patients’ characteristics. Somatic mutations occurred in EGFR, KRAS, HER2 and BRAF genes, and these mutations have been detected in 55.7%, 5.2%, 2.0% and 0.7% patients, respectively. The EGFR mutation is the most prevalent targetable mutation in Taiwan. EML4-ALK translocations have been found in 9.8% of patients with wild-type EGFR. The molecular profiling of advanced NSCLC is critical to optimal therapeutic decision-making. The patient characteristics, such as mutation profiles, protein expression profiles, drug-resistance profiles, molecular oncogenic mechanisms and patient subgroup systems together offer new strategies for personalized treatments and patient care.

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“…Broadly, lung cancer cases are separated into relatively rare small-cell lung cancers and the more common non-small cell lung cancers (NSCLCs), which account for 85–90% of the total caseload ( 2 , 3 ). Although many advances in the treatment and diagnosis of this condition have been made in recent years, NSCLC patients still face relatively poor 5-year overall survival (OS) outcomes ( 4 , 5 ). Platinum-based dual chemotherapy remains the standard approach to treating patients with advanced-stage disease ( 6 , 7 ).…”

Section: Introductionmentioning

confidence: 99%

LncRNA SNHG7 promotes non-small cell lung cancer progression and cisplatin resistance by inducing autophagic activity

She¹,

He²,

Xiao³

et al. 2023

J Thorac Dis

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Background Cisplatin (DDP) is among the most widely used chemotherapeutic drugs for non-small cell lung cancer (NSCLC), yet the frequent emergence of chemoresistance serves as a major barrier to the treatment of this tumor type. Long non-coding RNAs (lncRNAs) have recently been shown to influence the ability of cells to resist particular chemotherapy drugs. The present study was developed to explore the role of the lncRNA SNHG7 as a regulator of NSCLC cell chemosensitivity. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to measure SNHG7 expression in NSCLC tissues from patients that were sensitive/resistant to DDP, correlations between SNHG7 expression levels and the patients’ clinicopathological characteristics were assessed, and the prognostic relevance of SNHG7 expression was examined via the Kaplan-Meier approach. In addition, SNHG7 expression was assessed in NSCLC cell lines that were DDP-sensitive or -resistant, while western blotting and immunofluorescence staining were employed to detect autophagy-associated protein expression in A549, A549/DDP, HCC827, and HCC827/DDP cells. NSCLC cell chemoresistance was quantified via the Cell Counting Kit-8 (CCK-8) assay approach, and flow cytometry was used to detect the apoptotic death of these tumor cells. The chemosensitivity of xenograft tumors in vivo was further assessed to validate the functional importance of SNHG7 as a regulator of NSCLC DDP resistance. Results Relative to paracancerous tissues, NSCLC tumors exhibited SNHG7 upregulation, and this lncRNA was further upregulated in DDP-resistant patients compared to chemosensitive patients. Consistently, higher SNHG7 expression levels were correlated with worse patient survival outcomes. DDP-resistant NSCLC cells were also found to exhibit higher levels of SNHG7 expression than chemosensitive cells, and knocking down this lncRNA enhanced the sensitivity of these cells to DDP treatment, resulting in impaired proliferation and higher rates of apoptotic death. Knocking down SNHG7 was also sufficient to suppress microtubule associated protein 1 light chain 3 beta (LC3B) and Beclin1 protein levels and promote p62 upregulation in vitro . The silencing of this lncRNA additionally inhibited the resistance of NSCLC xenograft tumors to DDP treatment in vivo. Conclusions SNHG7 can promote malignant behaviors and DDP resistance in NSCLC cells at least partly via the induction of autophagic activity.

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Cerebrospinal fluid as a medium of liquid biopsy in the management of patients with non-small-cell lung cancer having central nervous system metastasis

Cited by 7 publications

References 71 publications

Circ_0003028 enhances the proliferation and glycolytic capacity and suppresses apoptosis in non-small cell lung cancer cells via the miR-1305/miR-1322-SLC5A1 axis

Circ_0003028 enhances the proliferation and glycolytic capacity and suppresses apoptosis in non-small cell lung cancer cells via the miR-1305/miR-1322-SLC5A1 axis

State-of-the-Art Molecular Oncology of Lung Cancer in Taiwan

LncRNA SNHG7 promotes non-small cell lung cancer progression and cisplatin resistance by inducing autophagic activity

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