Low LKB1 Expression Results in Unfavorable Prognosis in Prostate Cancer Patients

Lu, Jiajia; Sun, Peng; Sun, Beibei; Wang, Chao

doi:10.12659/msm.894847

Cited by 7 publications

(5 citation statements)

References 39 publications

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“…There is only one study in the literature investigating LKB1 mRNA expression in human prostate tumor tissues (Lu et al, 2015). In contrast to our results, this study reports a significant decrease in the LKB1 mRNA expression in PCa tissues.…”

Section: Lkb1 In Prostate Pathogenesiscontrasting

confidence: 99%

“…Although investigating expression of the LKB1 protein to confirm mRNA expression levels would corroborate our results, unfortunately most of the samples made available for this study were not sufficient to analyze LKB1 protein expression by Western blotting in matched pairs of tissue specimens. However, for LKB1, a high degree of agreement between the mRNA and protein expression has been shown in PCa (Lu et al, 2015) as well as in cervical (Lao et al, 2014), pancreatic (Yang et al, 2015), and breast (Chen et al, 2016) cancers. A relevant study compared LKB1 protein expression in six benign prostatic tissue samples from cystoprostatectomy surgical specimens and 22 PCa tissue samples from radical retropubic prostatectomy surgical specimens (Grossi et al, 2015).…”

Section: Lkb1 In Prostate Pathogenesismentioning

confidence: 99%

“…Although mutations of LKB1 have been investigated in different tumors, they have not been analyzed in human PCa. On the other hand, LKB1 expression in human prostate tumors has been investigated only in a single study (Lu et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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No Tumor Suppressor Role for LKB1 in Prostate Cancer

Köseoğlu

Çelebi

Galamiyeva

et al. 2021

DNA and Cell Biology

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To elucidate the pathogenesis of prostate diseases, following in silico analysis, the LKB1 gene was selected for further investigation. The LKB1 gene has been associated with poor prognosis and is frequently mutated in different types of cancers. In this study, 50 benign prostatic hyperplasia (BPH) and 57 prostate cancer (PCa) tissues, including matched normal tissue for the patients, were analyzed by qRT-PCR and DNA sequencing for LKB1 expression and the mutation profile, respectively. Expression of LKB1 was increased in 60.7% of the PCa tissues compared with noncancerous tissue samples ( p £ 0.001). However, LKB1 expression was lower when compared with normal tissues in BPH ( p = 0.920). Four coding sequence alterations were detected in BPH. Three silent mutations were located in codons 9, 32, and 275 and a missense mutation was observed in codon 384. Six alterations were identified in the intronic regions of the LKB1 gene in both PCa and BPH. Five mutations were observed in both patient groups. A new alteration in intron 6 was observed in a patient with PCa. The LKB1 gene may be associated with benign transformations rather than the tumors in prostate pathogenesis when its expression and mutation status are considered. However, the mechanism of LKB1 in PCa needs further studies.

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Section: Lkb1 In Prostate Pathogenesiscontrasting

confidence: 99%

Section: Lkb1 In Prostate Pathogenesismentioning

confidence: 99%

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No Tumor Suppressor Role for LKB1 in Prostate Cancer

Köseoğlu

Çelebi

Galamiyeva

et al. 2021

DNA and Cell Biology

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“…A total of 4858 potentially relevant studies were identified in literature searches, of which 3374 were excluded as duplicate publications. After screening titles and abstracts, 50 studies were read in full, leading to 25 that were included in the meta-analysis12–36 (figure 1). Data from all 25 studies were meta-analysed to examine the potential correlation of LKB1 expression with clinicopathological characteristics.…”

Section: Resultsmentioning

confidence: 99%

Association between LKB1 expression and prognosis of patients with solid tumours: an updated systematic review and meta-analysis

Ren

Zhao

et al. 2019

BMJ Open

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ObjectivesLiver kinase B1 (LKB1) is considered a tumour suppressor that can control cell growth and metabolism. Whether LKB1 expression levels are related to clinicopathology and prognosis is controversial. This review aimed to quantitatively examine the latest evidence on this question.DesignAn updated systematic review and meta-analysis on the association between LKB1 expression and prognosis of patients with solid tumours were performed.Data sourcesEligible studies were identified through literature searches from database establishment until 15 June 2018 in the following databases: Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure and Wan Fang databases.Eligibility criteriaThe association between LKB1 expression and clinicopathological characteristics, overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) of patients with solid tumours were reported. Sufficient data were available to calculate the OR or HR and 95% CI.Data extraction and synthesisRelevant data were meta-analysed for OS, DFS, RFS and various clinical parameters.ResultsThe systematic review included 25 studies containing 6012 patients with solid tumours. Compared with patients with high LKB1 expression, patients with low expression showed significantly shorter OS in univariate analysis (HR=1.63, 95% CI 1.35 to 1.97, p<0.01) and multivariate analysis (HR=1.61, 95% CI 1.26 to 2.06, p<0.01). In contrast, the two groups showed similar DFS in univariate analysis (HR=1.49, 95% CI 0.73 to 3.01, p=0.27) as well as similar RFS in univariate analysis (HR=1.44, 95% CI 0.65 to 3.17, p=0.37) and multivariate analysis (HR=1.02, 95% CI 0.42 to 2.47, p=0.97). Patients with low LKB1 expression showed significantly worse tumour differentiation (OR=1.71, 95% CI 1.14 to 2.55, p<0.01), larger tumours (OR=1.68, 95% CI 1.24 to 2.27, p<0.01), earlier lymph node metastasis (OR=1.43, 95% CI 1.26 to 1.62, p<0.01) and more advanced tumour, node, metastases (TNM) stage (OR=1.80, 95% CI 1.56 to 2.07, p<0.01).ConclusionLow LKB1 expression predicts shorter OS, worse tumour differentiation, larger tumours, earlier lymph node metastasis and more advanced TNM stage. Low LKB1 expression may be a useful biomarker of poor clinicopathology and prognosis.

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“…LKB1, a serine/threonine kinase, has been indicated to function as a tumor suppressor in various human cancers via regulating cancer cell growth, metabolism, survival and polarity ( 17 ). Mutations of LKB1 protein, such as K78I, D17GN, W308C and L67P, result in the loss of its kinase activity, and have been identified in different cancers, including malignant melanoma, head and neck squamous cell carcinoma, breast cancer, lung cancer, hepatocellular carcinoma, pancreatic and biliary carcinoma, colorectal cancer, cervical adenocarcinoma and testicular cancer ( 18 – 22 ).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of LKB1 promotes tumor progression and predicts unfavorable prognosis in patients with glioma

et al. 2017

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The liver kinase B1 (LKB1)/5′-adenosine monophosphate-activated protein kinase pathway has been reported to facilitate glioma cell growth by improving growth conditions. To investigate the clinical significance of LKB1 in human gliomas western blot analysis and quantitative polymerase chain reaction experiments were performed. The present study demonstrated that LKB1 expression was markedly decreased at the messenger RNA and protein levels in 30 freshly prepared glioma tissues, compared with non-neoplastic brain tissues (P<0.001). Subsequently, immunohistochemical analysis demonstrated that LKB1 immunostaining in 180 glioma tissues was significantly decreased compared with that in the corresponding non-neoplastic brain tissues (P<0.001). Notably, this downregulation frequently occurred in high-grade gliomas, and statistical analysis revealed that low LKB1 expression was significantly associated with large tumor size (P=0.02), advanced World Health Organization grade (P=0.006) and low Karnofsky performance scale (P=0.01). The prognostic value of LKB1 expression in patients with glioma was additionally evaluated using Kaplan-Meier survival curves and Cox proportional hazards regression models. As a result, the overall survival time of patients with glioma with low LKB1 expression was shorter compared with that of patients with high LKB1 expression (P<0.001), and low LKB1 expression also indicated decreased survival time in patients with high-grade glioma (P<0.001). Collectively, the present data indicated that the downregulation of LKB1 was closely associated with the malignant degree of human gliomas, exhibiting lower expression at a higher grade. Notably, LKB1 may serve as a potential prognostic biomarker for patients with glioma following surgery.

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Low LKB1 Expression Results in Unfavorable Prognosis in Prostate Cancer Patients

Cited by 7 publications

References 39 publications

No Tumor Suppressor Role for LKB1 in Prostate Cancer

No Tumor Suppressor Role for LKB1 in Prostate Cancer

Association between LKB1 expression and prognosis of patients with solid tumours: an updated systematic review and meta-analysis

Downregulation of LKB1 promotes tumor progression and predicts unfavorable prognosis in patients with glioma

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