Oncogenic Alterations in Primary Human Lung-Tumors (Review)

Strebhardt, Klaus; Holtrich, Uwe; Bräuninger, Andreas; Karn, Thomas; Böhme, Beatrix; Doermer, A; Rübsamen‐Waigmann, Helga

doi:10.3892/or.1.1.195

Cited by 2 publications

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“…Ki-ras, c-fos, c-jun and c-erb B1) and tumor suppressor genes (p53, Rb), especially in primary tissues of NSCLC, are still limited (Rodenhuis et al, 1987(Rodenhuis et al, , 1988Slebos et al, 1990;Volm et al, 1993;Bongiorno et al, 1994;Takahashi et al, 1989;Harbour et al, 1988). Various members of the family of protein kinases are involved in the development of human neoplasms, but the knowledge of their role in primary NSCLC is also restricted (Bishop et al, 1991;Strebhardt et al, 1994). We have previously cloned cDNAs of novel protein kinases by PCR-mediated approaches to identify new genes which could be important for the development of lung cancer (Lake and Jelinek, 1993;Hamanaka et al, 1994;Holtrich et al, 1991Holtrich et al, , 1994BraÈ uninger et al, 1992;BoÈ hme et al, 1993;Karn et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of polo-like kinase (PLK) expression in non-small cell lung cancer

et al. 1997

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Our previous data indicate that the expression of the PLK gene which codes for a serine/threonine kinase is restricted to proliferating cells. In Northern blot experiments PLK mRNA expression was at the limit of detection in normal lung tissue but elevated in most samples of non-small cell lung cancer (NSCLC). A very low frequency of PLK transcripts was only found in bronchiolo-alveolar carcinomas. NSCLC patients whose tumors showed moderate PLK expression survived signi®cantly longer (5 year survival rate=51.8%) than those with high levels of PLK transcripts (24.2%, P=0.001). No statistically signi®cant correlation was found between PLK mRNA expression and age, sex, TNM status, histological type or degree of dierentiation. Interestingly, the prognosis of patients in postsurgical stages I and II was correlated with PLK expression (5 year survival rates in stage I: 69.1% (moderate PLK) ± 43.5% (high PLK), P=0.03 or in stage II: 51.9% (moderate PLK) ± 9.9% (high PLK), P=0.006). These results suggest that PLK mRNA expression provides a new independent prognostic indicator for patients with NSCLC.

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Section: Introductionmentioning

confidence: 99%

Prognostic significance of polo-like kinase (PLK) expression in non-small cell lung cancer

et al. 1997

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“…However, clinical efficacy of these targeted therapies in long-term treatments is often limited by the emergence of resistance mechanisms. Therefore, numerous new potential targets, including several cell cycle kinases, are under investigation in order to further improve patient survival 3 , 4 .…”

Section: Introductionmentioning

confidence: 99%

Towards Prognostic Profiling of Non-Small Cell Lung Cancer: New Perspectives on the Relevance of Polo-Like Kinase 1 Expression, the TP53 Mutation Status and Hypoxia

et al. 2017

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Background: Currently, prognosis of non-small cell lung cancer (NSCLC) patients is based on clinicopathological factors, including TNM stage. However, there are considerable differences in patient outcome within a similar staging group, even when patients received identical treatments. In order to improve prognostic predictions and to guide treatment options, additional parameters influencing outcome are required. Polo-like kinase 1 (Plk1), a master regulator of mitotic cell division and the DNA damage response, is considered as a new potential biomarker in this research area. While several studies reported Plk1 overexpression in a broad range of human malignancies, inconsistent results were published regarding the clinical significance hereof. A prognostic panel, consisting of Plk1 and additional biomarkers that are related to the Plk1 pathway, might further improve prediction of patient prognosis.Methods: In this study, we evaluated for the first time the prognostic value of Plk1 mRNA and protein expression in combination with the TP53 mutation status (next generation sequencing), induction of apoptotic cell death (immunohistochemistry for cleaved caspase 3) and hypoxia (immunohistochemistry for carbonic anhydrase IX (CA IX)) in 98 NSCLC adenocarcinoma patients.Results: Both Plk1 mRNA and protein expression and CA IX protein levels were upregulated in the majority of tumor samples. Plk1 mRNA and protein expression levels were higher in TP53 mutant samples, suggesting that Plk1 overexpression is, at least partially, the result of loss of functional p53 (<0.05). Interestingly, the outcome of patients with both Plk1 mRNA and CA IX protein overexpression, who also harbored a TP53 mutation, was much worse than that of patients with aberrant expression of only one of the three markers (p=0.001).Conclusion: The combined evaluation of Plk1 mRNA expression, CA IX protein expression and TP53 mutations shows promise as a prognostic panel in NSCLC patients. Moreover, these results pave the way for new combination strategies with Plk1 inhibitors.

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Oncogenic Alterations in Primary Human Lung-Tumors (Review)

Cited by 2 publications

References 0 publications

Prognostic significance of polo-like kinase (PLK) expression in non-small cell lung cancer

Prognostic significance of polo-like kinase (PLK) expression in non-small cell lung cancer

Towards Prognostic Profiling of Non-Small Cell Lung Cancer: New Perspectives on the Relevance of Polo-Like Kinase 1 Expression, the TP53 Mutation Status and Hypoxia

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