Evaluation of liver kinase B1 downstream signaling expression in various breast cancers and relapse free survival after systemic chemotherapy treatment
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Khoa Nguyen1,*, Andrew Rivera1,*, Madlin Alzoubi1, Henri Wathieu1, Shengli Dong2, Hassan Yousefi2, Margarite Matossian1, Suresh Alahari2, David Drewry3, Matthew Burow1 and Bridgette Collins-Burow1
1 Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA
2 Department of Biochemistry and Molecular Biology, LSUHSC School of Medicine, New Orleans, LA, USA
3 UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA
* These authors contributed equally to this work & are co-first authors
Keywords: LKB1; STK11; breast cancer; triple negative breast cancer; patient prognosis
Received: October 08, 2020 Accepted: March 15, 2021 Published: May 25, 2021
LKB1-signaling has prominent roles in cancer development and metastasis. This report evaluates LKB1-signaling pathway gene expression associations with patient survival in overall breast cancer, specific subtypes, as well as pre- and post-chemotherapy. Subtypes analyzed were based on intrinsic molecular subtyping and traditional biomarker classifications. Intrinsic molecular subtypes included were Luminal-A, Luminal-B, HER2-enriched, and Basal-like. The biomarker subtypes assessed were Estrogen-Receptor Positive (ER+) and Negative (ER-), Wild-Type TP53 (WT-TP53) & Mutant-TP53, and Triple-Negative Breast Cancer (TNBC). Additionally, comparisons were made between these subtypes and breast cancer overall, and analyses between LKB1 signaling to patient survival before and after chemotherapy were made. We used the Kaplan-Meier Online Tool (KM Plotter) to correlate the relationship between mRNA expression of known LKB1 scaffolding proteins (CAB39 and LYK5), and downstream signaling targets (AMPK, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, PAK1, SIK1, SIK2, BRSK1, BRSK2, SNRK, and QSK), and patient survival across each subtype and treatment group. Our findings provide evidence that LKB1-signaling is associated with improved survival in overall breast cancer. Stratification into breast cancer subtypes show a more complicated relationship; NUAK2, for example, is correlated with improved survival in ER- but is worse in ER+ breast cancer. In evaluating the association of LKB1-signaling pathway expression with relapse free survival of varying breast cancer tumors exposed to chemotherapy or treatment-naive tumors, our data provides baseline knowledge for understanding the pathway dynamics that affect survival and therefore are linked to pathology. This establishes a foundation for studying LKB1 targets with the goal of identifying druggable targets.
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