A pilot study identifying a potential plasma biomarker for determining EGFR mutations in exons 19 or 21 in lung cancer patients

Pamungkas, Aryo Dimas; Medriano, Carl Angelo; Sim, Eunjung; Lee, Sung Yong; Park, Youngja

doi:10.3892/mmr.2017.6530

Cited by 8 publications

(6 citation statements)

References 54 publications

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“…In addition to proteins and metabolites, RNA transcripts, DNA, or epigenetic modifications of DNA can be used as biomarkers . Metabolomics has been used for biomarker discovery in the life, plant/food, and environmental sciences. − Recently developed configurations such as quadrupole time-of-flight (Q-TOF) tandem mass spectrometry in combination with liquid chromatography have improved metabolite screening by enhancing both mass resolution and mass accuracy. , Metabolomics investigations have been used to diagnose PCa numerous times; however, data in the Korean population is limited. Cho et al performed metabolic profiling of urine samples from PCa of Korean patients and observed an endogenous profile of corticosteroids even though the population was small …”

Section: Introductionmentioning

confidence: 99%

Noninvasive Serum Metabolomic Profiling Reveals Elevated Kynurenine Pathway’s Metabolites in Humans with Prostate Cancer

Khan

Choi

et al. 2019

J. Proteome Res.

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This study aimed to apply high-resolution metabolomics to detect compounds that may contribute significantly to prostate cancer (PCa) development. The test population's sera for evaluating the metabolic differences consisted of healthy control (n = 96) and PCa (n = 50) groups. PCa patients were further divided into two groups based on whether their PSA level was >4 (n = 25) or <4 (n = 25). Univariate analysis was performed with the false discovery rate (FDR) at q = 0.05 to determine significantly different metabolites. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) clearly distinguished healthy subjects from PCa groups, while no significant difference was observed in PCa patients with PSA level < 4 or > 4. Mummichog, in combination with the KEGG and MetaboAnalyst, showed that tryptophan metabolism along the kynurenine pathway was most significantly enriched, with −log (p) < 0.05. L-Tryptophan, kynurenine, anthranilate, isophenoxazine, glutaryl-CoA, (S)-3-hydroxybutanoyl-CoA, acetoacetyl-CoA, and acetyl-CoA were upregulated in correlation with the PSA level of PCa patients; in contrast, indoxyl, indolelactate, and indole-3-ethanol, involved in the alternative pathway, were downregulated in the PCa patients. Validation and quantification of potential metabolites by MS/MS further confirmed the disruption of tryptophan, kynurenine, and anthranilate, suggesting that the metabolites of this pathway are potential biomarkers in patients with PCa.

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Section: Introductionmentioning

confidence: 99%

Noninvasive Serum Metabolomic Profiling Reveals Elevated Kynurenine Pathway’s Metabolites in Humans with Prostate Cancer

Khan

Choi

et al. 2019

J. Proteome Res.

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“…For example, linoleic acid can enhance severe asthma by causing airway epithelial damage. In addition, non-small-cell lung cancer is usually characterized by the mutation of the epidermal growth factor receptor (EGFR), and the level of linoleic acid tends to increase significantly in cancer patients with more EGFR [25,26]. Therefore, linoleic acid is highly correlated with intestinal and pulmonary diseases and could be a key biomarker for monitoring the occurrence of pulmonary and intestinal diseases.…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Analysis of Microflora and Metabolites in the Development of Ulcerative Colitis into Colorectal Cancer Based on the Lung–Gut Correlation Theory

Tang

Liu²,

Ge³

et al. 2022

Molecules

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The lungs and large intestine can co-regulate inflammation and immunity through the lung–gut axis, in which the transportation of the gut microbiota and metabolites is the most important communication channel. In our previous study, not only did the composition of the gut microbiota and metabolites related to inflammation change significantly during the transition from ulcerative colitis (UC) to colorectal cancer (CRC), but the lung tissues also showed corresponding inflammatory changes, which indicated that gastrointestinal diseases can lead to pulmonary diseases. In order to elucidate the mechanisms of this lung–gut axis, metabolites in bronchoalveolar lavage fluid (BALF) and lung tissues were detected using UHPLC–Q-TOF-MS/MS technology, while microbiome characterization was performed in BALF using 16S rDNA sequencing. The levels of pulmonary metabolites changed greatly during the development of UC to CRC. Among these changes, the concentrations of linoleic acid and 7-hydroxy-3-oxocholic acid gradually increased during the development of UC to CRC. In addition, the composition of the pulmonary microbiota also changed significantly, with an increase in the Proteobacteria and an obvious decrease in the Firmicutes. These changes were consistent with our previous studies of the gut. Collectively, the microbiota and metabolites identified above might be the key markers related to lung and gut diseases, which can be used as an indication of the transition of diseases from the gut to the lung and provide a scientific basis for clinical treatment.

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“…Compared with the model group, XHW plus anlotinib significantly reduced plasma levels of fatty acids such as linoleic acid, arachidonic acid, and hexadecenoic acid to levels similar to those in the normal group. A pilot study indicated that plasma levels of linoleic acid were significantly higher in lung cancer patients with EGFR mutations and identified linoleic acid as a potential biomarker for the early detection of lung cancer ( 21 ). Lung tumor cell survival can be inhibited by blocking arachidonic acid metabolism; thus, targeting arachidonic acid action may be beneficial for cancer therapy ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

An Integrative Metabolomic and Network Pharmacology Study Revealing the Regulating Properties of Xihuang Pill That Improves Anlotinib Effects in Lung Cancer

Wang²,

Chen³

et al. 2021

Front. Oncol.

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Lung cancer ranks as a leading cause of death. Although targeted therapies usually trigger profound initial patient responses, these effects are transient due to drug resistance and severe side effects. Xihuang Pill (XHW) is a popular Chinese medicine formula that might benefit cancer patients when used as a complementary therapy. However, its underlying mechanism when combined with anticancer drugs is not clearly understood. Here, we used an integrated strategy to reveal the regulatory properties of XHW in increasing the antitumor activity of anlotinib in lung cancer. We evaluated the anti-lung cancer effect of XHW combined with anlotinib in mice bearing Lewis lung carcinoma (LLC). We applied untargeted metabolomics to identify the differences metabolism and found that XHW improved the effects of anlotinib on lung cancer. The components and targets related to the effects of XHW treatment on lung cancer were obtained through network pharmacology. Then, by integrating the biologically active components of XHW and anlotinib as well as the treatment-responsive metabolites and their related targets, an interaction network was constructed to evaluate the combination therapy. Finally, important protein candidates for this response were verified by immunohistochemistry of tumor tissues. The results showed that XHW significantly improved the inhibitory effect of anlotinib on tumor growth in LLC-bearing mice. Additionally, 12 differentially-abundant metabolites were identified by untargeted metabolomics in the XHW/anlotinib group compared with the XHW or anlotinib groups, and they were mainly enriched in fatty acid metabolism, lipid metabolism and amino acid metabolism pathways. Anlotinib, 23 components in Shexiang, 2 components in Niuhuang, 30 components in Ruxiang and 60 components in Moyao work together to act on 30 targets to regulate hexadecanoic acid (also named palmitic acid), linoleic acid, lactosylceramide, adrenaline, arachidonic acid and lysoPC(18:1(9Z)). The results of immunohistochemistry showed that XHW combined with anlotinib reduced the expression of PDGFRA in tumors. Overall, the key metabolites of XHW that enhances the efficacy of anlotinib were regulated by a multicomponent and multitarget interaction network. Our results suggested that anlotinib combined with XHW may be a promising strategy for the treatment of lung cancer.

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A pilot study identifying a potential plasma biomarker for determining EGFR mutations in exons 19 or 21 in lung cancer patients

Cited by 8 publications

References 54 publications

Noninvasive Serum Metabolomic Profiling Reveals Elevated Kynurenine Pathway’s Metabolites in Humans with Prostate Cancer

Noninvasive Serum Metabolomic Profiling Reveals Elevated Kynurenine Pathway’s Metabolites in Humans with Prostate Cancer

A Comprehensive Analysis of Microflora and Metabolites in the Development of Ulcerative Colitis into Colorectal Cancer Based on the Lung–Gut Correlation Theory

An Integrative Metabolomic and Network Pharmacology Study Revealing the Regulating Properties of Xihuang Pill That Improves Anlotinib Effects in Lung Cancer

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