Phosphorylated-Akt overexpression is associated with a higher risk of brain metastasis in patients with non-small cell lung cancer

Jin, Yu; Yuan, Ye; Yi, Minxiao; Hu, Han; Liu, Bo; Li, Qianxia

doi:10.1016/j.bbrep.2019.100625

Cited by 9 publications

(10 citation statements)

References 28 publications

(31 reference statements)

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“…Akt signaling plays an important role in cancer survival, proliferation and metastasis [ 11 ]. Akt signaling is commonly deregulated in cancers; in particular, Akt is overactivated in human lung cancer [ 45 ]. Akt, a serine/threonine kinase, is phosphorylated and activated by several external stimuli through transmembrane proteins, including receptor tyrosine kinases, integrins and cytokine receptors [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

Antitumor activities of Aspiletrein A, a steroidal saponin from Aspidistra letreae, on non-small cell lung cancer cells

Nguyen

Seephan

et al. 2021

BMC Complement Med Ther

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Background Lung cancer is one of the leading causes of death worldwide due to its strong proliferative and metastatic capabilities. The suppression of these aggressive behaviors is of interest in anticancer drug research and discovery. In recent years, many plants have been explored in order to discover new bioactive secondary metabolites to treat cancers or enhance treatment efficiency. Aspiletrein A (AA) is a steroidal saponin isolated from the whole endemic species Aspidistra letreae in Vietnam. Previously, elucidation of the structure of AA and screening of its cytotoxic activity against several cancer cell lines were reported. However, the antitumor activities and mechanisms of action have not yet been elucidated. In this study, we demonstrated the anti-proliferative, anti-migrative and anti-invasive effects of AA on H460, H23 and A549 human lung cancer cells. Methods MTT, wound healing and Transwell invasion assays were used to evaluate the anti-proliferation, anti-migration and anti-invasion effects of AA, respectively. Moreover, the inhibitory effect of AA on the activity of protein kinase B (Akt), a central mediator of cancer properties, and apoptotic regulators in the Bcl-2 family proteins were investigated by Western blotting. Results AA exhibits antimetastatic effects in human lung cancer cells through the inhibition of the pAkt/Akt signaling pathway, which in turn resulted in a significant inhibitory effect of AA on the migration and invasion of the examined lung cancer cells. Conclusions Aspiletrein A may be a potent inhibitor of protein kinase B (Akt). Hence, AA could be further explored as a potential antimetastatic lead compound.

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Section: Discussionmentioning

confidence: 99%

Antitumor activities of Aspiletrein A, a steroidal saponin from Aspidistra letreae, on non-small cell lung cancer cells

Nguyen

Seephan

et al. 2021

BMC Complement Med Ther

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“…For the hub gene PPL, the corresponding protein was reported to interact with AKT1 protein (van den Heuvel et al, 2002;Wang et al, 2008), suggesting its possible role as a localization signal in AKT1-mediated signaling. Notably, many studies have shown that aberrant Akt activation is associated with the development of many tumors (Steelman et al, 2008;Jin et al, 2019). Both David et al (2004) and Lim et al (2007) reported that p-Akt overexpression can be used as an indicator of poor prognosis in NSCLC.…”

Section: Gene Module Analysismentioning

confidence: 99%

“…EPS8 is a crucial molecule that mediates EGFR-induced activation of Akt (Innocenti, 2003) and PPL proteins as a localization signal in AKT1-mediated signaling by interacting with AKT1 (van den Heuvel et al, 2002;Wang et al, 2008). Akt activation is well known to be associated with the development of many tumors (Steelman et al, 2008;Jin et al, 2019), and it can also prevent FoxO3a, a tumor suppressor, from binding to EPS8. Moreover, it was reported that EGFR, via a U0126-sensitive ERK1/2 pathway, controls the transcriptional upregulation of SCN9A to promote cellular invasion in NSCLC cell lines (Campbell et al, 2013).…”

Section: Survival Analysismentioning

confidence: 99%

A Novel Method to Efficiently Highlight Nonlinearly Expressed Genes

et al. 2020

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For precision medicine, there is a need to identify genes that accurately distinguish the physiological state or response to a particular therapy, but this can be challenging. Many methods of analyzing differential expression have been established and applied to this problem, such as t-test, edgeR, and DEseq2. A common feature of these methods is their focus on a linear relationship (differential expression) between gene expression and phenotype. However, they may overlook nonlinear relationships due to various factors, such as the degree of disease progression, sex, age, ethnicity, and environmental factors. Maximal information coefficient (MIC) was proposed to capture a wide range of associations of two variables in both linear and nonlinear relationships. However, with MIC it is difficult to highlight genes with nonlinear expression patterns as the genes giving the most strongly supported hits are linearly expressed, especially for noisy data. It is thus important to also efficiently identify nonlinearly expressed genes in order to unravel the molecular basis of disease and to reveal new therapeutic targets. We propose a novel nonlinearity measure called normalized differential correlation (NDC) to efficiently highlight nonlinearly expressed genes in transcriptome datasets. Validation using six real-world cancer datasets revealed that the NDC method could highlight nonlinearly expressed genes that could not be highlighted by t-test, MIC, edgeR, and DEseq2, although MIC could capture nonlinear correlations. The classification accuracy indicated that analysis of these genes could adequately distinguish cancer and paracarcinoma tissue samples. Furthermore, the results of biological interpretation of the identified genes suggested that some of them were involved in key functional pathways associated with cancer progression and metastasis. All of this evidence suggests that these nonlinearly expressed genes may play a central role in regulating cancer progression.

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“…Therefore, treatment of patients with NSCLC and BMs is a major concern for patients and clinicians 23 . BM is one of the most challenging aspects of the clinical treatment of NSCLC patients 24 . In the examined trials, 7–13,15‐21 BM incidence was lower in the PCI than in the control group (0–20.3% vs 11–54%).…”

Section: Discussionmentioning

confidence: 96%

“…23 BM is one of the most challenging aspects of the clinical treatment of NSCLC patients. 24 In the examined trials, [7][8][9][10][11][12][13][15][16][17][18][19][20][21] BM incidence was lower in the PCI than in the control group (0-20.3% vs 11-54%). The study, RTOG 0214, 9 Eight studies on OS were included in this meta-analysis, and all found that PCI did not affect the survival rate of NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Treatment and toxic effects of prophylactic cranial irradiation in stage II–III non–small cell lung cancer: A meta‐analysis

Wang

Wen

et al. 2020

Asia-Pac J Clncl Oncology

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Objective: To determine the role of prophylactic cranial irradiation (PCI) in non-small cell lung cancer (NSCLC) patients using meta-analysis. Methods: PubMed, Embase, the Cochrane Database of Systematic Review and the China National Knowledge Infrastructure databases were systematically searched for studies published between 1 January 1980 and 31 March 2019. Search terms included "non-small cell lung cancer," "prophylactic cranial irradiation" and "clinical trials." The research data extracted from above studies was analyzed by Review Manager 5.3 and Stata12.0 software. The outcomes included development of brain metastases (BMs), overall survival (OS), disease-free survival (DFS), BMs for different diagnoses, toxicity, quality of life (QoL). Results: Fifteen trials (nine RCTs and six non-RCTs) involving 2418 NSCLC patients met the inclusion criteria. There was a significant reduction in the risk of developing BM in patients who received PCI compared with those who did not (95% CI, 0.20-0.37; P < 0.00001). PCI significantly reduced the BM of squamous cell carcinoma (P = 0.02), but not for adenocarcinoma (P = 0.07) and other pathological types (P = 0.29). There was a significant increase in DFS for the PCI compared to the non-PCI group (P = 0.006); however, OS did not significantly differ (P = 0.15). In addition, fatigue significantly increased in the PCI group (P = 0.0002). Cognitive disturbance showed no significant difference between PCI and non-PCI groups (P = 0.06). Conclusion: This study showed that, compared with non-PCI, PCI significantly decreased the incidence of NSCLC BM and improved the DFS of patients, and reduced the BM rate from squamous cell carcinoma. However, it showed no effect on OS and the BM rate of adenocarcinoma and other pathological types of tumors. There were limited data concerning PCI-related toxicity and QoL.

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Phosphorylated-Akt overexpression is associated with a higher risk of brain metastasis in patients with non-small cell lung cancer

Cited by 9 publications

References 28 publications

Antitumor activities of Aspiletrein A, a steroidal saponin from Aspidistra letreae, on non-small cell lung cancer cells

Antitumor activities of Aspiletrein A, a steroidal saponin from Aspidistra letreae, on non-small cell lung cancer cells

A Novel Method to Efficiently Highlight Nonlinearly Expressed Genes

Treatment and toxic effects of prophylactic cranial irradiation in stage II–III non–small cell lung cancer: A meta‐analysis

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