Up‐regulation of LIMK1 expression in prostate cancer is correlated with poor pathological features, lymph node metastases and biochemical recurrence

Huang, Jiaofeng; Wu, Yupeng; Lin, Yunzhi; Cai, Hai; Chen, Shao‐Hao; Sun, Xiong‐Lin; Li, Xiaodong; Wei, Yong; Zheng, Qing‐Shui; Xu, Ning; Xue, Xue‐Yi

doi:10.1111/jcmm.15138

Cited by 18 publications

(16 citation statements)

References 47 publications

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“…Through integrative analysis, we found co-occurrence of BRCA2 mutation and LIMK1 alternation (Fig. 2b), and high expression of LIMK1 in prostate cancer indicates a poor outcome [23]. Germline DDR mutations, especially loss-of function BRCA2 mutations, are found primarily in prostate cancer presenting a more aggressive phenotype and a poor prognosis [24].…”

Section: Dna Damage Repair Pathwaymentioning

confidence: 94%

TP53 alterations of hormone-naïve prostate cancer in the Chinese population

Liu

Guo

Zhu

et al. 2020

Prostate Cancer Prostatic Dis

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Background Prostate cancer (PCa) shows racial disparity in clinical and genomic characteristics, and Asian patients with PCa often present with more aggressive phenotypes at diagnosis. The ability of TP53 to serve as a prognostic biomarker of PCa has been well studied in Western populations. However, no studies to date have examined the role of TP53 in the disparities of primary hormone-naïve prostate cancer (HNPC) between Chinese and Western populations. Methods We collected prostate tumors and matched normal tissues or blood samples to perform targeted next-generation sequencing of 94 Chinese primary localized HNPC samples, and correlated these genomic profiles with clinical outcomes. The OncoKB knowledge database was used to identify and classify actionable alterations. Results The aberrations of PTEN, CDK12, and SPOP in Chinese HNPC samples were similar to those in the Western samples. However, we demonstrated an association of a high frequency of TP53 alterations (21/94) with a relatively higher percentage of alterations in the Wnt signaling pathway (15/94) in Chinese HNPC. Additionally, we highlighted alterations of LRP1B as accounting for a high proportion of PCa and found more frequent alterations in CDH1 in Chinese PCa. Of these, only CDH1 alteration was associated with rapid biochemical recurrence (BCR). However, we verified that TP53 status was at the core of the genomic alteration landscape in Chinese HNPC with putative driver mutations because of the strong connections with other signaling pathways. The mutually exclusive relationship between alterations in TP53 and Wnt/ CTNNB1 further molecularly characterizes subsets of prostate cancers. Moreover, the alteration of KMT2C was more likely to co-occur with TP53 alteration, indicating a more aggressive phenotype of PCa, which was associated with sensitivity to treatment with poly ADT-ribose polymerase (PARP) inhibitors. Conclusions Detection of TP53 alterations has clinical utility for guiding precision cancer therapy for HNPC, especially in the Chinese population.

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Section: Dna Damage Repair Pathwaymentioning

confidence: 94%

TP53 alterations of hormone-naïve prostate cancer in the Chinese population

Liu

Guo

Zhu

et al. 2020

Prostate Cancer Prostatic Dis

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“…Many studies about the oncogenic role of LIMK1 in several human cancers have been emerged in recent years, including gastric cancer, pancreatic cancer, as well as lung cancer ( McConnell et al, 2011 ; Chen et al, 2013 ). Furthermore, it is reported that LIMK1 is upregulated in various cancers and associates with an unfavorable prognosis ( Huang et al, 2020 ). However, the expression of LIMK1 and its prognostic value has not been fully investigated in lung adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have characterized LIMK1 as an important biomarker for poor prognosis and associated upregulated mRNA expression of LIMK1 with poor overall survival in many cancers. In prostate cancer, it is reported that elevated LIMK1 is positively associated with higher Gleason Scores and incidence of metastasis, as well as poor clinical outcome and reduced survival ( Davila et al, 2007 ; Mardilovich et al, 2015 ; Huang et al, 2020 ). In ovarian cancer, Zhang et al (2012) demonstrated that overexpression of LIMK1 is significant correlated with severity and poor differentiation level of ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have confirmed that ectopic expression of LIMK1 was associated with the progression of several tumor types, such as colorectal cancer, gastric cancer, prostate cancer, and breast cancer ( Davila et al, 2003 ; McConnell et al, 2011 ; You et al, 2015 ; Liao et al, 2017 ). A paper from Huang et al (2020) indicated that the upregulation of LIMK1 is correlated with lymph node metastasis and poor biochemical-free survival in prostate cancer. In pancreatic cancer, Vlecken and Bagowski (2009) reported that knockdown of LIMK1 can lead to an inhibition of invasion and metastatic behavior, as well as suppression of pancreatic cancer cell-induced angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Upregulation of LIMK1 Is Correlated With Poor Prognosis and Immune Infiltrates in Lung Adenocarcinoma

Zhou

Zhang

et al. 2021

Front. Genet.

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BackgroundProtein-coding gene LIM Domain Kinase 1 (LIMK1) is upregulated in various tumors and reported to promote tumor invasion and metastasis. However, the prognostic values of LIMK1 and correlation with immune infiltrates in lung adenocarcinoma are still not understood. Therefore, we evaluated the prognostic role of LIMK1 and its correlation with immune infiltrates in lung adenocarcinoma.MethodsTranscriptional expression profiles of LIMK1 between lung adenocarcinoma tissues and normal tissues were downloaded from the Cancer Genome Atlas (TCGA). The LIMK1 protein expression was assessed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas. Receiver operating characteristic (ROC) curve was used to differentiate lung adenocarcinoma from adjacent normal tissues. Kaplan-Meier method was conducted to assess the effect of LIMK1 on survival. Protein-protein interaction (PPI) networks were constructed by the STRING. Functional enrichment analyses were performed using the “ClusterProfiler” package. The relationship between LIMK1 mRNA expression and immune infiltrates was determined by tumor immune estimation resource (TIMER) and tumor-immune system interaction database (TISIDB).ResultsThe expression of LIMK1 in lung adenocarcinoma tissues was significantly upregulated than those in adjacent normal tissues. Increased LIMK1 mRNA expression was associated with lymph node metastases and high TNM stage. The ROC curve analysis showed that with a cutoff level of 4.908, the accuracy, sensitivity, and specificity for LIMK1 differentiate lung adenocarcinoma from adjacent controls were 69.5, 93.2, and 71.9%, respectively. Kaplan-Meier survival analysis showed lung adenocarcinoma patients with high- LIMK1 had a worse prognosis than those with low- LIMK1 (43.1 vs. 55.1 months, P = 0.028). Correlation analysis indicated LIMK1 mRNA expression was correlated with tumor purity and immune infiltrates.ConclusionUpregulated LIMK1 is significantly correlated with poor survival and immune infiltrates in lung adenocarcinoma. Our study suggests that LIMK1 can be used as a biomarker of poor prognosis and potential immune therapy target in lung adenocarcinoma.

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“…Previous studies have shown that the expression of LIMK1 may affect tumor progression and is related to the peritoneal metastasis of colorectal cancer, gastric cancer and other tumors [8][9][10]. In addition, the up-regulation of LIMK1 is associated with prostate cancer metastasis and lower survival rate [11]. In addition, in pancreatic tumors, knockdown of LIMK1 can inhibit tumor invasion and metastasis, as well as inhibit angiogenesis [12,13].…”

Section: Introductionmentioning

confidence: 99%

The Expression of LIMK1 is Related to the Poor Prognosis and Immune Function of Hepatocellular Carcinoma

Peng

Fan

Zhu

et al. 2021

Preprint

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Background: According to reports, LIMK1 may have the effect of promoting tumor progression. However, the effect of the expression of LIMK1 on the healing of patients with hepatocellular carcinoma and its effect on the immune function are still not clear. Therefore, we analyzed the effect of LIMK1 on the healing of patients with hepatocellular carcinoma and its correlation with immunity through bioinformatics analysis.Methods: Download the transcriptional expression profile of LIMK1 in hepatocellular carcinoma tissues and normal tissues in TCGA, and study its expression in hepatocellular carcinoma. Study the expression of LIMK1 in hepatocellular carcinoma through CPTAC and HPA database. The Kaplan-Meier method was used to evaluate the effect of LIMK1 expression on the survival of patients with hepatocellular carcinoma. Use the STRING database to construct a protein-protein interaction (PPI) network. Use the "ClusterProfiler" package for feature-rich analysis. Use TISIDB database and Xiantao platform to study the relationship between LIMK1 mRNA expression and immune infiltration.Results: The expression of LIMK1 in hepatocellular carcinoma tissues was significantly up-regulated. Increased expression of LIMK1 mRNA is related to high TNM staging. In the ROC curve, when the cut-off level is 1.813, the sensitivity and specificity of LIMK1 to distinguish hepatocellular carcinoma from adjacent controls are 80.7% and 86%, respectively.The Kaplan-Meier curve shows that the higher the expression of LIMK1, the worse the survival of patients with hepatocellular carcinoma (42.2 months vs. 70 months, P = 0.001). Correlation analysis studies have shown that the expression of LIMK1 mRNA in hepatocellular carcinoma is related to immune cell infiltration.Conclusion: Up-regulation of LIMK1 may affect the survival rate and immune invasion of hepatocellular carcinoma. Studies have shown that LIMK1 may be related to the poor prognosis of hepatocellular carcinoma, and has a certain relationship with the immune infiltration of hepatocellular carcinoma.

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Up‐regulation of LIMK1 expression in prostate cancer is correlated with poor pathological features, lymph node metastases and biochemical recurrence

Cited by 18 publications

References 47 publications

TP53 alterations of hormone-naïve prostate cancer in the Chinese population

TP53 alterations of hormone-naïve prostate cancer in the Chinese population

Upregulation of LIMK1 Is Correlated With Poor Prognosis and Immune Infiltrates in Lung Adenocarcinoma

The Expression of LIMK1 is Related to the Poor Prognosis and Immune Function of Hepatocellular Carcinoma

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