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Clinical significance of atypical protein kinase C (PKC? and PKC?) and its relationship with yes-associated protein in lung adenocarcinoma.

ABSTRACT: BACKGROUND:Protein kinase C iota (PKC?) and protein kinase C zeta (PKC?) are two atypical protein kinase (aPKC) enzymes that contribute to cell proliferation and cancer development. The Hippo/YAP pathway is commonly disrupted and upregulated in cancers. Herein, the expression patterns and clinical relevance of PKC? and PKC? are evaluated in relation to YAP, a downstream effector of Hippo, in lung adenocarcinoma (LAC). The protein and mRNA expression levels of PKC?, PKC?, YAP, and their phosphorylated forms, namely p-PKC?, p-PKC? and p-YAP, are evaluated in relation to clinicopathological factors, including patient survival. METHODS:A total of 200 primary LAC tissue samples were examined by immunohistochemistry for PKC?, p-PKC?, PKC?, p-PKC?, YAP, and p-YAP protein expression. Sixty pairs of LAC and non-neoplastic lung tissue samples were assessed for PRKCI, PRKCZ, and YAP mRNA levels. PKC?, p-PKC?, PKC?, and p-PKC? protein expression were evaluated by Western blot analysis in the PC9 and PC9/GR LAC cell lines with YAP modulation. RESULTS:LAC demonstrated cytoplasmic PKC?, p-PKC?, PKC?, and p-PKC? immunostaining patterns. Positive aPKC protein expressions were related with poor patient survival. Especially, increased p-PKC? protein expression was significantly correlated with higher pathological stage and shortened overall survival. YAP overexpression contributes phosphorylation of PKC? and PKC? protein expression in the LAC cell line. CONCLUSIONS:PKC? and PKC? are related to YAP in LAC. PKC? and PKC? play distinct roles in LAC; specifically, p-PKC? overexpression is suggested to underlie factors that indicate a poor prognosis.

SUBMITTER: Kim KH

PROVIDER: S-EPMC6693135 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Clinical significance of atypical protein kinase C (PKCι and PKCζ) and its relationship with yes-associated protein in lung adenocarcinoma.

Kim Kyung-Hee KH Chung Chaeuk C Kim Jin-Man JM Lee Dahye D Cho Sang Yeon SY Lee Tae Hee TH Cho Hyun Jin HJ Yeo Min-Kyung MK

BMC cancer 20190814 1

<h4>Background</h4>Protein kinase C iota (PKCι) and protein kinase C zeta (PKCζ) are two atypical protein kinase (aPKC) enzymes that contribute to cell proliferation and cancer development. The Hippo/YAP pathway is commonly disrupted and upregulated in cancers. Herein, the expression patterns and clinical relevance of PKCι and PKCζ are evaluated in relation to YAP, a downstream effector of Hippo, in lung adenocarcinoma (LAC). The protein and mRNA expression levels of PKCι, PKCζ, YAP, and their p ...[more]

PMID: 31412817

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Project description:Non-small cell lung cancer is a subtype of adenocarcinoma, which has previously shown positive responses to gefitinib. The aim of the current study was to determine a clinical profile of gefitinib-induced disease controls for patients with lung adenocarcinoma. Retrospective evaluation of the clinical characteristics of 52 lung adenocarcinoma patients, enrolled at the Zhejiang Cancer Hospital (Hangzhou, China) between October 2004 and August 2008, was undertaken. All patients received gefitinib (250 mg/day orally) until disease progression or until an unacceptable toxicity was observed. Of the 52 patients, complete response (CR) and partial response (PR) rates were 23.1% (12/52) and 57.7% (30/52), respectively. An additional 19.2% (10/52) of patients demonstrated stable disease (SD) after three months of treatment with gefitinib. Disease control was observed in the primary lesion, and tumor metastasis to the lungs, brain, adrenal glands, pleura, peritoneum, pericardium, bone and lymph nodes was identified. The one-year progression-free survival (PFS) and overall survival (OS) rates were 74.8 and 78.0%, respectively. Multivariate analysis revealed that female patients were associated with significantly longer survival times when compared with males (hazard ratio, 0.077; 95% confidence interval [CI], 0.007-0.083; P=0.035). One-year PFS and OS rates in CR, PR and SD patients were 77.8, 73.9 and 33.3%, and 89.2, 79.8 and 33.7%, respectively, although neither difference was identified to be statistically significant. In addition, the median OS of SD patients was 12 months (95% CI, 7.2-16.8 months). Brain metastasis was the major site of disease progression (23.1%). Gefitinib treatment for patients with lung adenocarcinoma showed a marked long-term survival benefit, even in SD patients. However, further studies are required to analyze the efficacy of gefitinib in penetrating the blood-brain barrier in order to prolong PFS in patients with lung adenocarcinoma.

Dataset Information

Clinical significance of atypical protein kinase C (PKC? and PKC?) and its relationship with yes-associated protein in lung adenocarcinoma.

Publications

Clinical significance of atypical protein kinase C (PKCι and PKCζ) and its relationship with yes-associated protein in lung adenocarcinoma.

Similar Datasets

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