Clinicopathologic features and prognostic implications of NOK/STYK1 protein expression in non-small cell lung cancer

Chen, Peng; Li, Weimiao; Lü, Qiang; Wang, Jian; Yan, Xiaolong; Zhang, Zhipei; Li, Xiaofei

doi:10.1186/1471-2407-14-402

Cited by 23 publications

(29 citation statements)

References 26 publications

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“…Our own previous studies have demonstrated that the overexpression of NOK is significantly associated with lymphatic metastasis in NSCLC. 12 However, the relationship between NOK and EMT has not yet been elucidated and fully defined mechanistically. In this study, we verify that NOK has a tumorigenic activity and may correlate with tumor metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…The K-M survival analysis revealed that patients with high NOK expression (median survival time: 12.0 months) showed a trend of shorter OS than those of low NOK expression (median survival time: 19.5 months, P=0.0790; Supplementary Figure 1), which was consistent with our previous study. 12 The association between NOK expression and the clinicopathological variables was analyzed (…”

Section: The Upregulated Expression Of Nok In Human Nsclc Tissues Is mentioning

confidence: 99%

“…Aberrant expression of NOK has been found in a wide range of cancers, including lung, ovarian, breast, colorectal, prostate, and renal cell cancers. [11][12][13][14][15][16] Recently, NOK was found to be capable of promoting the malignant transformation of tumors in some cancers by activating the PI3K/AKT pathway. 17,18 All these studies indicate that NOK overexpression is associated with cancer progression, and NOK can induce EMT by activating the Akt pathway.…”

Section: Introductionmentioning

confidence: 99%

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<p>Aberrantly High Expression Of NOK/STYK1 Is Tightly Associated With The Activation Of The AKT/GSK3β/N-Cadherin Pathway In Non-Small Cell Lung Cancer</p>

Huang

Xiong

et al. 2019

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High metastasis is a leading risk factor for the survival of non-small cell lung cancer (NSCLC) and epithelial-mesenchymal transition (EMT) is a vital step of metastasis. The expression of novel oncogene with kinase domain (NOK) has been observed in some human malignancies, including non-small cell lung cancer (NSCLC); however, the biological function of NOK in NSCLC remains unclear. In the study, we explored the function of NOK in NSCLC, with an aim to elucidate the relevant underlying mechanisms. Patients and methods: We investigate the expression of NOK, p-Akt, p-GSK-3β, E-cadherin and N-cadherin expression by immunohistochemical analysis using tissue microarrays of 72 paired NSCLC samples of cancerous and adjacent normal tissues. The associations between NOK expression and clinicopathological factors, overall survival, other proteins were assessed. Immunofluorescence analysis of NSCLC tissues was performed to study the location of NOK, Akt and GSK-3β. Up or down-regulated of NOK were conducted in two NSCLC cell lines to analyze its impact on AKT/GSK3β pathway. Results: Statistical analysis revealed NOK expression increased in NSCLC tissues compared with normal tissues (P<0.05). It also showed that low NOK expression were associated with a higher possibility of non-lymphatic metastasis, an early pN stage and clinical stage (P<0.05). Moreover, NOK expression was positively correlated with the expression of oncogene p-Akt (Thr308), p-GSK-3β (Ser9) and N-cadherin (P<0.05). Immunofluorescence analysis of NSCLC tissues revealed that NOK is co-located with Akt and GSK-3β. Further study in NSCLC cell lines revealed that NOK overexpression can activate the AKT/GSK3β pathway. Conversely, knockdown of NOK can suppress the AKT/GSK3β pathway. Conclusion: Our results suggest that NOK overexpression correlated significantly with lymphatic metastasis, advanced pN and clinical stage in NSCLC. And NOK may promote EMT by activating the AKT/GSK3β/N-cadherin pathway in NSCLC.

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Section: Discussionmentioning

confidence: 99%

Section: The Upregulated Expression Of Nok In Human Nsclc Tissues Is mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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<p>Aberrantly High Expression Of NOK/STYK1 Is Tightly Associated With The Activation Of The AKT/GSK3β/N-Cadherin Pathway In Non-Small Cell Lung Cancer</p>

Huang

Xiong

et al. 2019

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“…In addition, the prognostic and therapeutic significance of STYK1 overexpression in human malignant diseases has also been revealed. Chen P et al recently demonstrated that increased expression of STYK1 protein correlates with poor prognosis of patients with non-small cell lung cancer [ 17 ]. Nirasawa S et al provided evidence that STYK1 is a novel drug resistance factor and could be a potential predictor of the therapeutic response in acute leukemia [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Serine threonine tyrosine kinase 1 is a potential prognostic marker in colorectal cancer

Chen

Cai

et al. 2015

BMC Cancer

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BackgroundAberrant expression of serine threonine tyrosine kinase 1 (STYK1) has been reported in several human malignancies including colorectal cancer (CRC). However, the prognostic significance of STYK1 expression in CRC remains unknown.MethodsSTYK1 protein expression in paraffin-embedded CRC specimens was determined immunohistochemically. The correlation of STYK1 expression with clinicopathologic features was assessed in a cohort containing 353 patients with primary CRC. Kaplan-Meier and Cox proportional regression analyses were used to evaluate the association between STYK1 expression and patients’ survival.ResultsSTYK1 expression was frequently up-regulated in CRC clinical samples at the protein levels and was significantly associated with tumor differentiation grade (p = 0.030), lymph node metastasis (p = 0.004), TNM stage (p = 0.007) and patient death (p < 0.001). Kaplan-Meier analysis indicated that patients with high intratumoral STYK1 expression had a significantly shorter disease-specific survival (DSS) than those with low expression (p < 0.001). Importantly, high levels of STYK1 protein predicted poor DSS for both stage II (p < 0.001) and stage III (p = 0.004) patients. Furthermore, multivariate analyses revealed that STYK1 protein expression was an independent prognostic indicator for both stage II (hazard ratio [HR], 2.472; p = 0.001) and stage III (HR, 2.001; p = 0.004) patients.ConclusionsOur results suggest that increased STYK1 protein expression correlates with disease progression and metastasis and may serve as a predictor of poor survival in CRC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1285-y) contains supplementary material, which is available to authorized users.

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“…All stained sections were examined by two independent investigators who were blinded to the clinical features and outcomes. The immunohistochemical (IHC) staining scores were based on the following criteria: (i) the percentage of positive cells (0, ≤5%; 1, 6%‐25%; 2, 26%‐50%; 3, 51%‐75%; and 4, >75%); (ii) the staining intensity (0, no color; 1, yellow; 2, brown; and 3, tan); and (iii) the two grades were multiplied together and specimens were assigned to one of four levels: 0, negative (−); 1‐4, weakly positive (+); 5‐8, moderately positive (++); and 9‐12, strongly positive (+++) . To investigate the correlation of protein expression, (−) and (+) were considered as low expression, and (++) and (+++) were considered as high expression.…”

Section: Methodsmentioning

confidence: 99%

Cell cycle‐related and expression‐elevated protein in tumor overexpression is associated with proliferation behaviors and poor prognosis in non‐small‐cell lung cancer

Zheng

Xia

et al. 2018

Cancer Science

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The cell cycle‐related and expression‐elevated protein in tumor (CREPT) is overexpressed in several human malignancies. However, the clinical relevance of CREPT expression and its biological role in non‐small‐cell lung cancer (NSCLC) remains unclear. In this study, we detected the expression of CREPT in both NSCLC tissues and cell lines by immunohistochemistry, Western blot analysis, and RT‐PCR. The correlation between CREPT expression and clinicopathologic features was analyzed in 271 NSCLC patients. The prognostic value of CREPT expression was evaluated by Kaplan–Meier analysis and Cox regression analysis. CREPT was overexpressed in Calu‐1 cell lines by using plasmid vector and its biological function was explored both in vitro and in vivo. We found that CREPT was significantly overexpressed in NSCLC compared with paired adjacent non‐tumor tissues, and the expression level of CREPT was correlated with tumor differentiation, lymph node metastasis, and clinical stage. Kaplan–Meier analysis showed that the recurrence‐free survival and overall survival of high CREPT expression groups were significantly shorter than those of the low CREPT expression group. Multivariate analysis identified that CREPT might be an independent biomarker for the prediction of NSCLC prognosis. Overexpression of CREPT increased cell proliferation and enhanced the migration and invasion ability of Calu‐1 cells (a human NSCLC cell line with relative low CRPET expression) in vitro. Moreover, CREPT overexpression promoted tumor growth in a nude mice model. These results suggest that CREPT is closely relevant to the proliferation of NSCLC cells and it might be a potential prognostic marker in NSCLC patients.

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Clinicopathologic features and prognostic implications of NOK/STYK1 protein expression in non-small cell lung cancer

Cited by 23 publications

References 26 publications

<p>Aberrantly High Expression Of NOK/STYK1 Is Tightly Associated With The Activation Of The AKT/GSK3β/N-Cadherin Pathway In Non-Small Cell Lung Cancer</p>

<p>Aberrantly High Expression Of NOK/STYK1 Is Tightly Associated With The Activation Of The AKT/GSK3β/N-Cadherin Pathway In Non-Small Cell Lung Cancer</p>

Serine threonine tyrosine kinase 1 is a potential prognostic marker in colorectal cancer

Cell cycle‐related and expression‐elevated protein in tumor overexpression is associated with proliferation behaviors and poor prognosis in non‐small‐cell lung cancer

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