Dataset Information

Label Free proteomics on NSCLC isogenic cell lines

ABSTRACT: Since both KRAS mutations and LKB1 inactivating alterations affect cellular metabolism, it seems propitious to discern metabolic effects induced by the single oncogenic events from those elicited by their co-occurrence, with the ultimate aim to potentially exploit metabolic dependencies for novel therapeutic modalities. With these considerations in mind, we knocked-out the LKB1 gene in well-characterized NSCLC cell clones harboring KRAS WT or mutant G12C proteins (13,30). We obtained an isogenic system in which KRAS mutation and LKB1 inactivation were individually or concomitantly present. The effects of the genetic lesions individually or together on cell metabolism were investigated in these isogenic NSCLC cells by means of an integrated survey of proteomics, stable and dynamic metabolomics and functional in-vitro strategies.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Cell Culture

DISEASE(S): Non-small Cell Lung Carcinoma

SUBMITTER: Laura Brunelli

LAB HEAD: Roberta Pastorelli

PROVIDER: PXD007838 | Pride | 2019-11-14

REPOSITORIES: Pride

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Publications

Co-occurring KRAS mutation/LKB1 loss in non-small cell lung cancer cells results in enhanced metabolic activity susceptible to caloric restriction: an in vitro integrated multilevel approach.

Caiola Elisa E Falcetta Francesca F Giordano Silvia S Marabese Mirko M Garassino Marina C MC Broggini Massimo M Pastorelli Roberta R Brunelli Laura L

Journal of experimental & clinical cancer research : CR 20181204 1

<h4>Background</h4>Non-small-cell lung cancer (NSCLC) is a heterogeneous disease, with multiple different oncogenic mutations. Approximately 25-30% of NSCLC patients present KRAS mutations, which confer poor prognosis and high risk of tumor recurrence. About half of NSCLCs with activating KRAS lesions also have deletions or inactivating mutations in the serine/threonine kinase 11 (LKB1) gene. Loss of LKB1 on a KRAS-mutant background may represent a significant source of heterogeneity contributin ...[more]

PMID: 30514331

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Project description:The success of targeted therapies creates a need to discriminate tumors accurately by their histological and genetic characteristics. Here, we used cDNA microarray analysis to identify gene expression profiles and single markers that recapitulate the pathological and genetic background (i.e., BRAF, EGFR, KRAS, LKB1, PIK3CA, and TP53 gene alterations) of non-small cell lung cancer (NSCLC). Gene expression profiles were determined for 6 normal lung tissues and 69 lung tumors from patients diagnosed with NSCLC. We performed an unsupervised hierarchical clustering with the most variably expressed transcript to investigate whether there was evidence for natural grouping samples based on similarity in gene expression profiles. We examined the relationship between the clusters of tumors and patient and tumor characteristics such as gender, smoking status, histological type, degree of differentiation, tumor size, lymph node involvement and genetic background. We used a supervised analysis to identify the genes that are important for distinguishing subgroups of tumors defined by histological type. Moreover, we used this supervised approach to search for markers that characterize those tumors carrying EGFR, KRAS, PIK3CA and TP53 alterations. We identify several genes with characteristic patterns of expression in each tumor histological type (adenocarcinoma and squamous cell carcinoma) and we found that the presence of EGFR mutations result in a particular expression profile. Keywords: Transciption profiling of tumors with different histological and genetic background. We analyzed 69 NSCLC tumors. All the samples were characterized by histological type and by the presence of alterations at genes that are known to be involved in lung carcinogenesis. Mutational analysis of BRAF, EGFR, KRAS, and LKB1 is provided only for adenocarcinomas and analysis of alterations at PIK3CA gene (mutational analysis or gene amplification by FISH analysis) is provided only for 47 of the tumors. We analyzed gene expression profiles to identify those genes that are differentially expressed between two subgroups by t-test: 1) adenocarcinomas vs. squamous cell carcinomas; 2) tumors with mutation at EGFR gene vs. wild type tumors; 3) tumors with mutation at KRAS gene vs. wild type tumors; 4) tumors with mutation at TP53 gene vs. wild type tumors; 5) tumors with alterations (mutation or gene amplification) at PIK3CA gene vs. wild type tumors.

Dataset Information

Label Free proteomics on NSCLC isogenic cell lines

Publications

Co-occurring KRAS mutation/LKB1 loss in non-small cell lung cancer cells results in enhanced metabolic activity susceptible to caloric restriction: an in vitro integrated multilevel approach.

Similar Datasets

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