{"doi":"10.1016/j.lungcan.2023.107361","title":"Comparative bioinformatic analysis of KRAS, STK11 and KEAP1 (co-)mutations in non-small cell lung cancer with a special focus on KRAS G12C","abstract":null,"journal":"Lung Cancer","year":2023,"id":638754,"datarank":0.47670807455219194,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.0,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1265071,"name":"Christina Katharina Kuhn","orcid":"0000-0001-6705-9048","position":1,"is_corresponding":false},{"id":1659274,"name":"Hubert Wirtz","orcid":null,"position":2,"is_corresponding":false},{"id":1659275,"name":"Hans-Jürgen Seyfarth","orcid":null,"position":3,"is_corresponding":false},{"id":1659276,"name":"Armin Frille","orcid":null,"position":4,"is_corresponding":false},{"id":1176469,"name":"Florian Lordick","orcid":"0000-0001-8591-9339","position":5,"is_corresponding":false},{"id":1659277,"name":"Ulrich T. Hacker","orcid":null,"position":6,"is_corresponding":false},{"id":1659278,"name":"Ulrike Obeck","orcid":null,"position":7,"is_corresponding":false},{"id":1659279,"name":"Mathias Stiller","orcid":null,"position":8,"is_corresponding":false},{"id":455353,"name":"Hendrik Bläker","orcid":"0000-0002-2497-8172","position":9,"is_corresponding":false},{"id":88033,"name":"Maximilian von Laffert","orcid":"0000-0002-8799-0427","position":10,"is_corresponding":false},{"id":1659273,"name":"Myriam Boeschen","orcid":"0000-0002-9277-1296","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Comparative bioinformatic analysis of KRAS, STK11 and KEAP1 (co-)mutations in non-small cell lung cancer with a special focus on KRAS G12C","abstract":"<h4>Objectives</h4>Mutations in STK11 (STK11<sup>MUT</sup>) and KEAP1 (KEAP1<sup>MUT</sup>) occur frequently in non-small cell lung cancer (NSCLC) and are often co-mutated with KRAS. Several studies linked the co-occurrence of KRAS<sup>MUT</sup> + STK11<sup>MUT</sup>, as well as KRAS<sup>MUT</sup> + KEAP1<sup>MUT</sup> to reduced response to immune checkpoint inhibitors (ICI) and even a negative impact on survival. Data focusing STK11 + KEAP1 co-mutations or the triple mutation (KRAS + STK11 + KEAP1) are scarce. The recent availability of KRAS-G12C inhibitors increases the clinical relevance of those co-mutations in KRAS-mutated NSCLC.<h4>Materials and methods</h4>We present a comprehensive bioinformatic analysis encompassing six datasets retrieved from cBioPortal.<h4>Results</h4>Independent of the treatment, triple mutations and STK11<sup>MUT</sup> + KEAP1<sup>MUT</sup> were significantly associated with a reduced overall survival (OS). Across treatments, OS of patients with a KRAS G12C triple mutation was significantly reduced compared to patients with KRAS G12C-only. Under ICI-therapy, there was no significant difference in OS between patients harboring the KRAS G12C-only and patients with the KRAS G12C triple mutation, but a significant difference between patients harboring KRAS non-G12C and KRAS non-G12C triple mutations. Triple mutated primary tumors showed a significantly increased frequency of distant metastases to bone and adrenal glands compared to KRAS-only mutated tumors. Additionally, our drug response analysis in cancer cell lines harboring the triple mutations revealed the WNT pathway inhibitor XAV-939 as a potential future drug candidate for this mutational situation.<h4>Conclusion</h4>The triple mutation status may serve as a negative prognostic and predictive factor across treatments compared to KRAS<sup>MUT</sup>-only. KRAS G12C generally seems to be a negative predictive marker for ICI-therapy.","is_dataset_classified":null,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37699269","pmcid":null,"openalex_id":"https://openalex.org/W4386573160","authors":[],"funders":[],"total_grants":0,"fwci":3.6499,"citation_percentile":0.94278928,"influential_citations":0,"citation_trend":[{"year":2024,"count":9},{"year":2025,"count":6},{"year":2026,"count":7}],"oa_status":"closed","license":"https://doi.org/10.15223/policy-004","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0169500223008991?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0169500223008991?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.lungcan.2023.107361","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37699269","host_type":"repository"}],"fields_of_study":["Lung Cancer Treatments and Mutations","Cancer Immunotherapy and Biomarkers","Melanoma and MAPK Pathways","Humans","Carcinoma, Non-Small-Cell Lung","Proto-Oncogene Proteins p21(ras)","Kelch-Like ECH-Associated Protein 1","Lung Neoplasms","NF-E2-Related Factor 2","Mutation","Computational Biology","Protein Serine-Threonine Kinases","AMP-Activated Protein Kinase Kinases"],"mesh_terms":["Kelch-Like ECH-Associated Protein 1","AMP-Activated Protein Kinase Kinases","Carcinoma, Non-Small-Cell Lung","Humans","Lung Neoplasms","Mutation","Proto-Oncogene Proteins p21(ras)","Protein Serine-Threonine Kinases","Computational Biology","NF-E2-Related Factor 2"],"keywords":["KRAS","STK11","Medicine","Mutation","Cancer research","Cancer","Oncology","Internal medicine","Biology","Gene","Colorectal cancer","Genetics"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T21:22:14.626089Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}