Metabolic network-based identification of plasma markers for non-small cell lung cancer

Abstract

Metabolic markers, offering sensitive information on biological dysfunction, play important roles in diagnosing and treating cancers. However, the discovery of effective markers is limited by the lack of well-established metabolite selection approaches. Here, we propose a network-based strategy to uncover the metabolic markers with potential clinical availability for non-small cell lung cancer (NSCLC). First, an integrated mass spectrometry-based untargeted metabolomics was used to profile the plasma samples from 43 NSCLC patients and 43 healthy controls. We found that a series of 39 metabolites were altered significantly. Relying on the human metabolic network assembled from Kyoto Encyclopedia of Genes and Genomes (KEGG) database, we mapped these differential metabolites to the network and constructed an NSCLC-related disease module containing 23 putative metabolic markers. By measuring the PageRank centrality of molecules in this module, we computationally evaluated the network-based importance of the 23 metabolites and demonstrated that the metabolism pathways of aromatic amino acids and long-chain fatty acids provided potential molecular targets of NSCLC (i.e., IL4l1 and ACOT2). Combining network-based ranking and support-vector machine modeling, we further found a panel of eight metabolites (i.e., pyruvate, tryptophan, and palmitic acid) that showed a high capability to differentiate patients from controls (accuracy > 97.7%). In summary, we present a meaningful network method for metabolic marker discovery and have identified eight strong candidate metabolites for NSCLC diagnosis.

Regulatory roles of ACSL5 in anti-tumor function of Palmitic acid (C16:0) via ERK signaling pathway

“…Similarly, ACSL5 has potential prognostic value in a variety of tumors. For instance, sporadic colorectal adenocarcinoma may have an independent prognostic marker for early recurrence called ACSL5 [17]. Patients with both ER-positive and ER-negative breast cancer may have a better prognosis if ACSL5 is highly expressed [18].…”

Progress of the acyl-Coenzyme A thioester hydrolase family in cancer

“…In addition to ACOT 7, ACOT 2 has also been implicated in NSCLC, and Guo et al. ( 35 ) demonstrated based on the human metabolic network that ACOT 2 can participate as a potential molecular target of NSCLC in the metabolic pathways of aromatic amino acids and long-chain fatty acids.…”

Metabolomic biomarkers in liquid biopsy: accurate cancer diagnosis and prognosis monitoring

“…In another study, by combining differential metabolites obtained by MS with a metabolic network based on Kyoto Encyclopedia of Genes and Genomes database, Guo et al. constructed a metabolite panel (including pyruvate) specifically for non-small cell lung cancer (NSCLC) with a diagnostic accuracy of almost 98% ( 19 ). Subsequently, by applying the NMR technique, Ye et al.…”

“…Abnormalities in tryptophan metabolism in tumor cells have been extensively studied and metabolites involved in tryptophan catabolism, such as kynurenine, have emerged as targets for anti-tumor therapy ( 102 ). Alterations in tryptophan levels in the biological fluids of lung cancer patients have been observed in three studies, two of which found that patients with NSCLC had elevated blood tryptophan levels compared to healthy controls ( 19 , 43 ). In contrast, a study based on sputum metabolomics observed the opposite trend in patients with lung cancer ( 46 ), and the difference in the distribution of tryptophan in blood and sputum may be the result of increased tryptophan consumption by tumor cells.…”