Clinical Relevance of Liver Kinase B1(LKB1) Protein and Gene Expression in Breast Cancer

Chen, I‐Chun; Chang, Yuan‐Ching; Lu, Yen‐Shen; Chung, Kuei-Pin; Huang, Chiun‐Sheng; Lu, Tzu‐Pin; Kuo, Wen‐Hung; Wang, Mingyang; Kuo, Kuan‐Ting; Wu, Pei-Fang; Hsueh, Tsu-Hsin; Shen, Chen‐Yang; Lin, Ching‐Hung; Cheng, Ann‐Lii

doi:10.1038/srep21374

Cited by 20 publications

(20 citation statements)

References 27 publications

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“…The expression of LKB1 in tumours cells was previously reported as 71%, which is slightly lower than the expression reported in our population (78%) [24]. This could be explained by the age of the population, as our study included patients 70 years or older, while the previously reported data included four groups with median ages of 48, 54, 61 and 62 years [24]. In our study, the association between LKB1 positivity and the factors mentioned above suggests its role as a possible poor prognostic indicator.…”

Section: Discussioncontrasting

confidence: 78%

“…In our study, the association between LKB1 positivity and the factors mentioned above suggests its role as a possible poor prognostic indicator. The association of LKB1 expression with high histological grade suggests a poor prognostic indication as reported previously, where IHC was used for the detection of LKB1 protein expression [24]. While in vitro studies reported a negative correlation between both LKB1 mutation and grade and VEGF and a positive correlation with hormone receptor expression [1,3,12,25], these studies analysed LKB1 using Western blot and RT-PCR [1,3,11].…”

Section: Discussionmentioning

confidence: 98%

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Liver Kinase B1—A Potential Therapeutic Target in Hormone-Sensitive Breast Cancer in Older Women

Syed

Green

Morgan

et al. 2019

Cancers

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Background: The role of liver kinase B1 (LKB1), a serine/threonine kinase, has been described in the development of PeutzJagher’s syndrome, where a proportion (~45%) of patients have developed breast cancer in their lifetime. Cell line studies have linked LKB1 with oestrogen receptors (ER) and with the Adenosine monophosphate-activated protein kinase (AMPK) pathway for energy metabolism. However, limited studies have investigated protein expression of LKB1 in tumour tissues and its intracellular relationships. This study aimed to investigate the intracellular molecular relationships of LKB1 in older women with early operable primary breast cancer and its correlation with long-term clinical outcome. Methods: Between 1973 and 2010, a consecutive series of 1758 older (≥70 years) women with T0-2N0-1M0 breast carcinoma were managed in a dedicated facility. Of these, 813 patients underwent primary surgery, and 575 had good quality tumour samples available for tissue microarray construction. LKB1 was assessed in 407 cases by indirect immunohistochemistry (IHC). Tumours with 30% or more of cells with cytoplasmic LKB1 expression were considered positive. LKB1 expression was compared with tumour size, histological grade, axillary lymph node stage, ER, PgR, EGFR, HER2, HER3, HER4, BRCA1&2, p53, Ki67, Bcl2, Muc1, E-Cadherin, CD44, basal (CK5, CK5/6, CK14 and CK17) and luminal (CK7/8, CK18 and CK19) cytokeratins, MDM2 and MDM4, and correlated with long-term clinical outcome. Results: Positive LKB1 expression was seen in 318 (78.1%) patients, and was significantly associated with high tumour grade, high Ki67, over-expression of HER2, VEGF, HER4, BRCA2, MDM2 and negative expression of CD44 (p < 0.05). There was no significant correlation with tumour size, axillary lymph node status, ER, PgR, p53, basal or luminal cytokeratins, Bcl2, Muc1, EGFR, HER3, MDM4, E-cadherin and BRCA1. LKB1 did not show any significant influence on survival in the overall population; however, in those patients receiving adjuvant endocrine therapy for ER positive tumours, those with positive LKB1 had significantly better 5-year breast cancer specific survival when compared to those without such expression (93% versus 74%, p = 0.03). Conclusion: LKB1 expression has shown association with poor prognostic factors in older women with breast cancer. However, LKB1 expression appears to be associated with better survival outcome among those patients receiving adjuvant endocrine therapy. Further research is required to explore its potential role as a therapeutic target.

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Section: Discussioncontrasting

confidence: 78%

Section: Discussionmentioning

confidence: 98%

Liver Kinase B1—A Potential Therapeutic Target in Hormone-Sensitive Breast Cancer in Older Women

Syed

Green

Morgan

et al. 2019

Cancers

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“… 66 Importantly, LKB1 is a tumour suppressor kinase and its loss promotes breast cancer metastasis and invasion. 67 , 68 …”

Section: Discussionmentioning

confidence: 99%

miR-622 is a novel potential biomarker of breast carcinoma and impairs motility of breast cancer cells through targeting NUAK1 kinase

et al. 2020

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Background Aberrant expression of microRNAs (miR) has been proposed as non-invasive biomarkers for breast cancers. The aim of this study was to analyse the miR-622 level in the plasma and in tissues of breast cancer patients and to explore the role of miR-622 and its target, the NUAK1 kinase, in this context. Methods miR-622 expression was analysed in plasma and in tissues samples of breast cancer patients by q-RT-PCR. Bioinformatics programs, luciferase assay, public dataset analysis and functional experiments were used to uncover the role of miR-622 and its target in breast cancer cells. Results miR-622 is downregulated in plasma and in tissues of breast cancer patients respect to healthy controls and its downregulation is significantly associated with advanced grade and high Ki67 level. Modulation of miR-622 affects the motility phenotype of breast cancer cells. NUAK1 kinase is a functional target of miR-622, it is associated with poor clinical outcomes of breast cancer patients and is inversely correlated with miR-622 level. Conclusions miR-622/NUAK1 axis is deregulated in breast cancer patients and affects the motility phenotype of breast cancer cells. Importantly, miR-622 and NUAK1 hold promises as biomarkers and as targets for breast cancers.

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“…Of note, it is hard to associate the expression profile of LKB1 with a specific BC subtype, since the cohorts studied give rise to contradictory results. This could be due to the difference in the cohorts' size, the methods used to detect LKB1 (western blot, immunohistochemistry, RT-PCR…) and the fact that LKB1 localization is not always taken into account [14] [72] [78].…”

Section: Lkb1 a Potentiallymentioning

confidence: 99%

LKB1, A New Biomarker in Breast Cancer

Lattouf¹,

Poulard²,

Treilleux³

et al. 2016

JCT

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Breast cancer is the most common cancer in women worldwide. Estrogen signaling pathways have been identified as efficient targets of breast cancer therapy, given their key role in promoting breast tumor growth. Agents blocking estrogen-mediated pathways are routinely used in clinical applications in patients displaying estrogen-sensitive breast cancer subtypes; however intrinsic or acquired resistance to treatment often occurs or develops, thus limiting their efficacy. This limitation has highlighted an imperative need to identify new predictive biomarkers. Recent findings have highlighted a role for the Liver Kinase B1 (LKB1) in breast cancer tumorigenesis. LKB1 is a serine/threonine kinase mutated in Peutz-Jeghers syndrome (PJS), implicated in many cellular processes including energy metabolism, cell polarization and cell cycle arrest and has also been shown to play an essential role as a tumor suppressor gene by negatively regulating the mTOR pathway. This review provides an overview of previous findings and ongoing research on LKB1, and substantiates the use of this kinase as a potential prognostic and predictive biomarker of breast cancer.

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Clinical Relevance of Liver Kinase B1(LKB1) Protein and Gene Expression in Breast Cancer

Cited by 20 publications

References 27 publications

Liver Kinase B1—A Potential Therapeutic Target in Hormone-Sensitive Breast Cancer in Older Women

Liver Kinase B1—A Potential Therapeutic Target in Hormone-Sensitive Breast Cancer in Older Women

miR-622 is a novel potential biomarker of breast carcinoma and impairs motility of breast cancer cells through targeting NUAK1 kinase

LKB1, A New Biomarker in Breast Cancer

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