Lung cancer in young patients appears to have distinct clinicopathological features. The present study focused on the role of the serine/threonine kinase liver kinase B1 (LKB1), a known tumor suppressor gene, and its miRNA regulation in lung adenocarcinoma, particularly in young versus elderly patients. A total of 88 patients with lung adenocarcinoma were retrospectively analysed. A simultaneous quantification was performed of the expression of LKB1 mRNA and 15 microRNAs (miRNA/miRs; miRs -93, -96, -34a, -34c, -214, -33a, -30b, -145, -182, -30c, -183, -29b, -29c, -153 and -138) involved in the LKB1 pathway, as well as of 5 identified target mRNAs [cyclin D1 (CCND1), catenin β-1 (CTNNB1), lysyl oxidase (LOX), yes-associated protein 1 (YAP1) and survivin], using NanoString technology. KRAS mutations were investigated by pyrosequencing analysis. Patients ≤50 years were defined as a younger group, while patients >50 years old as an older group (n=44/group). No difference between the two groups was identified in terms of survival times analysed using the Kaplan-Meier method or KRAS mutations. Subsequently, the LKB1 signalling pathway was focused on, as a target for therapy in lung adenocarcinoma, and assessed with regards to clinicopathological features; we found that LOX levels in adenocarcinoma patients were significantly associated with histological subtype (P=0.03), stage (P<0.0001) and prognosis (P=0.02 for disease-free interval and P=0.005 for overall survival), but not with age. Furthermore, the miRNA target prediction model indicated that miR-93 and miR-30b appeared to have functional binding sites and downregulate the gene expression of LKB1 and LOX, respectively. In conclusion, young patients appeared have similar survival rates to elderly patients. The assessment of LKB1, its downstream genes and its regulation by miRNAs may have an impact on future research on lung adenocarcinoma in young and elderly patients. Further investigations will be necessary to elucidate the potential of this pathway as a novel target for therapy.

Expression profiling and microRNA regulation of the LKB1 pathway in young and aged lung adenocarcinoma patients.

Boldrini L
Primo
;
Giordano M
Secondo
;
Lucchi M;Melfi F
Penultimo
;
Fontanini G.
Ultimo
2018

Abstract

Lung cancer in young patients appears to have distinct clinicopathological features. The present study focused on the role of the serine/threonine kinase liver kinase B1 (LKB1), a known tumor suppressor gene, and its miRNA regulation in lung adenocarcinoma, particularly in young versus elderly patients. A total of 88 patients with lung adenocarcinoma were retrospectively analysed. A simultaneous quantification was performed of the expression of LKB1 mRNA and 15 microRNAs (miRNA/miRs; miRs -93, -96, -34a, -34c, -214, -33a, -30b, -145, -182, -30c, -183, -29b, -29c, -153 and -138) involved in the LKB1 pathway, as well as of 5 identified target mRNAs [cyclin D1 (CCND1), catenin β-1 (CTNNB1), lysyl oxidase (LOX), yes-associated protein 1 (YAP1) and survivin], using NanoString technology. KRAS mutations were investigated by pyrosequencing analysis. Patients ≤50 years were defined as a younger group, while patients >50 years old as an older group (n=44/group). No difference between the two groups was identified in terms of survival times analysed using the Kaplan-Meier method or KRAS mutations. Subsequently, the LKB1 signalling pathway was focused on, as a target for therapy in lung adenocarcinoma, and assessed with regards to clinicopathological features; we found that LOX levels in adenocarcinoma patients were significantly associated with histological subtype (P=0.03), stage (P<0.0001) and prognosis (P=0.02 for disease-free interval and P=0.005 for overall survival), but not with age. Furthermore, the miRNA target prediction model indicated that miR-93 and miR-30b appeared to have functional binding sites and downregulate the gene expression of LKB1 and LOX, respectively. In conclusion, young patients appeared have similar survival rates to elderly patients. The assessment of LKB1, its downstream genes and its regulation by miRNAs may have an impact on future research on lung adenocarcinoma in young and elderly patients. Further investigations will be necessary to elucidate the potential of this pathway as a novel target for therapy.
Boldrini, L; Giordano, M; Lucchi, M; Melfi, F; Fontanini, G.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/932203
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