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Altered lung tissue lipidomic profile in caspase-4 positive non-small cell lung cancer (NSCLC) patients.

ABSTRACT: Lung cancer is by far the leading cause of cancer death. Metabolomic studies have highlighted that both tumor progression and limited curative treatment options are partly due to dysregulated glucose metabolism and its associated signaling pathways. In our previous studies, we identified caspase-4 as a novel diagnostic tool for non-small cell lung cancer (NSCLC). Here, we analyzed the metabolomic profile of both plasma and tumor tissues of NSCLC patients stratified as caspase-4 positive or negative. We found that circulating caspase-4 was correlated to LDH. However, this effect was not observed in caspase-4 positive tumor tissues, where instead, fatty acid biosynthesis was favoured in that the malonic acid and the palmitic acid were higher than in non-cancerous and caspase-4 negative tissues. The glycolytic pathway in caspase-4 positive NSCLC tissues was bypassed by the malonic acid-dependent lipogenesis. On the other hand, the dysregulated glucose metabolism was regulated by a higher presence of succinate dehydrogenase (SDHA) and by the gluconeogenic valine which favoured Krebs' cycle. In conclusion, we found that the recently identified caspase-4 positive subpopulation of NSCLC patients is characterized by a lipidomic profile accompanied by alternative pathways to guarantee glucose metabolism in favour of tumor cell proliferation.

SUBMITTER: Terlizzi M

PROVIDER: S-EPMC7517963 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Altered lung tissue lipidomic profile in caspase-4 positive non-small cell lung cancer (NSCLC) patients.

Terlizzi Michela M Molino Antonio A Colarusso Chiara C Somma Pasquale P De Rosa Ilaria I Troisi Jacopo J Scala Giovanni G Salvi Rosario R Pinto Aldo A Sorrentino Rosalinda R

Oncotarget 20200922 38

Lung cancer is by far the leading cause of cancer death. Metabolomic studies have highlighted that both tumor progression and limited curative treatment options are partly due to dysregulated glucose metabolism and its associated signaling pathways. In our previous studies, we identified caspase-4 as a novel diagnostic tool for non-small cell lung cancer (NSCLC). Here, we analyzed the metabolomic profile of both plasma and tumor tissues of NSCLC patients stratified as caspase-4 positive or negat ...[more]

PMID: 33014287

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Project description:Lung cancers are a heterogeneous group of diseases with respect to biology and clinical behavior. Currently, diagnosis and classification are based on histological morphology and immunohistological methods for discrimination between two main histologic groups: small cell lung cancer (SCLC) and non-small cell lung cancer which account for 20% and 80% of lung carcinomas, respectively. NSCLCs, which are divided into the three major subtypes adenocarcinoma, squamous cell carcinoma and dedifferentiated large cell carcinoma, show different characteristics such as the expression of certain keratins or production of mucin and lack of neuroedocrine differentiation. The molecular pathogenesis of lung cancer involves the accumulation of genetic und epigenetic alterations including the activation of proto-oncogenes and inactivation of tumor suppressor genes which are different for lung cancer subgroups. The development of microarray technologies opened up the possibility to quantify the expression of a large number of genes simultaneously in a given sample. There are several recent reports on expression profiling on lung cancers but the analysis interpretation of the results might be difficult because of the heterogeneity of cellular components. The methods used for sample selection and processing can have a strong influence on the expression values obtained through microarray profiling. Laser capture microdissection (LCM) provides higher specificity in the selection of target cells compared to traditional bulk tissue selection methods, but at an increased processing cost. Here we describe the use of an expression microarray study on NSCLC samples and surrounding tissue, comparing macroscopic lung tumor and tissue samples (“grind and bind”), versus tumor and alveolar compartment cells laser capture microdissected (LCM) from the same macroscopic lung samples. In this study, a set of 31 pairs and one non-paired sample of macroscopic tumor and non-tumor samples (10 pairs and 1 non-paired sample squamous-cell carcinoma, 19 pairs and one non-paired samples adenocarcinoma, 2 pairs adeno-squamous-cell carcinoma) was selected for bulk/macro sampling. Of these 31 pairs and 2 non-paired samples, 16 pairs plus 15 non paired samples were reanalyzed using laser capture microdissection (LCM) for sampling the cells (7 pairs and 3 non-paired samples squamous-cell carcinoma, 8 pairs and 11 non-paired samples adeno carcinomas, 1 pair and 1 non paired sample Adeno-squamous-cell carcinoma). For macroscopic samples, 50 to 80 µg of tissue was used to isolate total RNA. Gene expression profile was determined using Affymetrix Human Genome Gene 1.0 ST genechip. For the LCM samples, from representative slides histologically confirmed and mapped by a pathologist, approximately 1000 cells/sample were collected by LCM;. cDNA was amplified using Nugen WT-Ovation One-Direct amplification system. Here we describe the use of an expression microarray study on NSCLC samples and surrounding tissue, comparing macroscopic lung tumor and tissue samples (“grind and bind”), versus tumor and alveolar compartment cells laser capture microdissected (LCM) from the same macroscopic lung samples.

Dataset Information

Altered lung tissue lipidomic profile in caspase-4 positive non-small cell lung cancer (NSCLC) patients.

Publications

Altered lung tissue lipidomic profile in caspase-4 positive non-small cell lung cancer (NSCLC) patients.

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