High-resolution metabolomic biomarkers for lung cancer diagnosis and prognosis

Qi, Shi-ang; Wu, Qian; Chen, Zhenpu; Zhang, Wei; Zhou, Yunyun; Mao, Kaining; Li, Jia; Li, Yuanyuan; Chen, Jie; Huang, Yang H.; Huang, Yunchao

doi:10.1038/s41598-021-91276-2

Cited by 58 publications

(39 citation statements)

References 44 publications

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“…Lung tumor cell survival can be inhibited by blocking arachidonic acid metabolism; thus, targeting arachidonic acid action may be beneficial for cancer therapy (22). High plasma levels of palmitic acid were associated with life expectancy for lung cancer patients, which could be used for early lung cancer diagnosis (23)(24)(25). Our results suggest that XHW improves the efficacy of anlotinib by restoring endogenous fatty acid homeostasis.…”

Section: Discussionmentioning

confidence: 72%

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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Section: Discussionmentioning

confidence: 72%

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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“…Fatty acids have a key role as structural components of the membrane matrix but can also act as secondary messengers and serve as fuel sources for energy production, and these features are also very relevant under cancer development [59]. Regarding this, very recently Qi, Wu, Chen, Zhang, Zhou, Mao, Li, Li, Chen, Huang, and Huang [18] reported that plasma levels of saturated fatty acids (SFAs), such as dodecanoic acid, were significantly decreased in cancer groups. In turn, altered plasma levels of decanoic acid were reported as a putative new diagnostic biomarker in colorectal cancer [60] and the serum level of octanoic acid were found to predict the efficacy of chemotherapy against the same type of cancer [61].…”

Section: Metabolic Pathwaysmentioning

confidence: 99%

“…Different studies have shown the potential of such metabolic strategies using human biofluids-including plasma [10], serum [11,12], sweat [13], sputum [14], or urine [10,15,16]. Such metabolic studies incorporating data information from all metabolites found in human biofluids involve fewer variables than genomics and transcriptomics studies [17] but are still complex and hard to analyse [18,19]. To overcome this challenge, researchers focus their attention on subsets of the human metabolites produced by the cells as the volatile organic metabolites (VOMs).…”

Section: Introductionmentioning

confidence: 99%

Urinary Volatomic Expression Pattern: Paving the Way for Identification of Potential Candidate Biosignatures for Lung Cancer

et al. 2022

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The urinary volatomic profiling of Indian cohorts composed of 28 lung cancer (LC) patients and 27 healthy subjects (control group, CTRL) was established using headspace solid phase microextraction technique combined with gas chromatography mass spectrometry methodology as a powerful approach to identify urinary volatile organic metabolites (uVOMs) to discriminate among LC patients from CTRL. Overall, 147 VOMs of several chemistries were identified in the intervention groups—including naphthalene derivatives, phenols, and organosulphurs—augmented in the LC group. In contrast, benzene and terpenic derivatives were found to be more prevalent in the CTRL group. The volatomic data obtained were processed using advanced statistical analysis, namely partial least square discriminative analysis (PLS-DA), support vector machine (SVM), random forest (RF), and multilayer perceptron (MLP) methods. This resulted in the identification of nine uVOMs with a higher potential to discriminate LC patients from CTRL subjects. These were furan, o-cymene, furfural, linalool oxide, viridiflorene, 2-bromo-phenol, tricyclazole, 4-methyl-phenol, and 1-(4-hydroxy-3,5-di-tert-butylphenyl)-2-methyl-3-morpholinopropan-1-one. The metabolic pathway analysis of the data obtained identified several altered biochemical pathways in LC mainly affecting glycolysis/gluconeogenesis, pyruvate metabolism, and fatty acid biosynthesis. Moreover, acetate and octanoic, decanoic, and dodecanoic fatty acids were identified as the key metabolites responsible for such deregulation. Furthermore, studies involving larger cohorts of LC patients would allow us to consolidate the data obtained and challenge the potential of the uVOMs as candidate biomarkers for LC.

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“…Metabolomics in a clinical setting supports the identif cation of metabolic biomarkers for cancer detection and surveillance [24]. For exampl high-resolution metabolomics was used to identify the top 5, 10, and 20 metabolites from plasma using HPLC coupled with a Q-Exactive high-resolution mass spectrometer [51 The identification and analysis of high-frequency metabolomic biomarkers with tyrosin on top were reported in a review for breast cancer [51] and a recent study by a Frenc cohort utilized untargeted metabolomics in breast cancer to predict disease outcome [52 Figure 2 depicts the hierarchical interrelationships among the omics.…”

Section: Metabolomics: the "Supra-omic"mentioning

confidence: 99%

The Integration of Metabolomics with Other Omics: Insights into Understanding Prostate Cancer

Resurreccion

Fong

2022

Metabolites

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Our understanding of prostate cancer (PCa) has shifted from solely caused by a few genetic aberrations to a combination of complex biochemical dysregulations with the prostate metabolome at its core. The role of metabolomics in analyzing the pathophysiology of PCa is indispensable. However, to fully elucidate real-time complex dysregulation in prostate cells, an integrated approach based on metabolomics and other omics is warranted. Individually, genomics, transcriptomics, and proteomics are robust, but they are not enough to achieve a holistic view of PCa tumorigenesis. This review is the first of its kind to focus solely on the integration of metabolomics with multi-omic platforms in PCa research, including a detailed emphasis on the metabolomic profile of PCa. The authors intend to provide researchers in the field with a comprehensive knowledge base in PCa metabolomics and offer perspectives on overcoming limitations of the tool to guide future point-of-care applications.

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High-resolution metabolomic biomarkers for lung cancer diagnosis and prognosis

Cited by 58 publications

References 44 publications

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

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

Urinary Volatomic Expression Pattern: Paving the Way for Identification of Potential Candidate Biosignatures for Lung Cancer

The Integration of Metabolomics with Other Omics: Insights into Understanding Prostate Cancer

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