Expression and clinical significance of A-kinase anchor protein 4 in lung adenocarcinoma tissue.
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ABSTRACT:
SUBMITTER: Li HM
PROVIDER: S-EPMC4846614 | biostudies-other | 2016 Apr
REPOSITORIES: biostudies-other
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Project description: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.
| S-EPMC6693135 | biostudies-literature
Project description:OBJECTIVE:To explore the expression patterns of transcription factor SOX12 in lung adenocarcinoma and its significance in the diagnosis and prognosis of the malignancy. METHODS:Large cancer genome databases were used to analyze SOX12 expression level in lung adenocarcinoma. Immunohistochemistry (IHC) and semiquantitative PCR were used to detect the expression of SOX12 in 36 specimens of lung adenocarcinoma tissues, 15 adjacent tissues and 21 normal lung tissues. The prognostic value of SOX12 in lung adenocarcinoma and lung squamous cell carcinoma were analyzed using Kaplan-Meier Plotter database, and the relationship between SOX12 expression and the overall survival (OS) and progression free survival (PPS) of the patients were analyzed. RESULTS:Analysis of TCGA database and GEO (GSE40419) database showed that SOX12 expression levels were significantly higher in in lung adenocarcinoma than in normal lung tissues (P < 0.001). The results of IHC and semiquantitative PCR revealed that SOX12 was expressed at significantly higher levels in lung adenocarcinoma than in normal lung tissues (P < 0.001). Kaplan-Meier survival analysis showed that patients with lung adenocarcinoma positive for SOX12 had a significantly shorter OS and PPS time than those negative for SOX12 (P < 0.05), but SOX12 positivity did not significantly affect OS and PPS of patients with lung squamous cell carcinoma. CONCLUSIONS:High expression levels of SOX12 in lung adenocarcinoma are significantly associated with a poor OS of the patients, suggesting the value of SOX12 to assist in early diagnosis and prognostic evaluation of lung adenocarcinoma.
| S-EPMC6765647 | biostudies-literature
Project description:The role of stimulator of interferon genes [STING, also known as transmembrane protein 173 (TMEM173)] in various human cancers has begun to emerge. However, the clinical value of STING in lung adenocarcinoma (LUAD) remains elusive. This study aims to elucidate the clinical significance of STING expression and methylation in LUAD. Here, through analyzing data from public resources, we found that both the mRNA and protein expression of STING were reduced in lung cancer. Moreover, lower expression of STING was associated with a worse prognosis in LUAD, but not lung squamous cell carcinoma (LUSC). Of note, higher methylation of STING was found in LUAD and had the potential to distinguish LUAD tissues from adjacent non-tumor lung tissues and correlated with unfavorable outcomes. Furthermore, the methylation of STING could serve as an independent prognostic indicator for both the overall survival (OS) and disease-free survival (DFS) of LUAD patients. Additionally, the constructed nomogram exhibited a favorable predictive accuracy in predicting the probability of 1- and 2-year OS. Our findings suggest that the mRNA expression, and especially the DNA methylation of STING, have the potential to be prognostic indicators for LUAD patients.
| S-EPMC9385651 | biostudies-literature
Project description:ObjectiveTo explore the expression of secreted phosphoprotein 1 (SPP1) in lung adenocarcinoma (LUAD), and evaluate its relationship with clinicopathological characteristics and prognosis of LUAD, and analyze the advantages of SPP1 as a potential prognostic marker in LUAD.MethodsThe expression of SPP1 in normal lung tissue and LUAD was analyzed from the Cancer Cell Line Encyclopedia (CCLE), Gene Expression Omnibus (GEO), and Human Protein Atlas (HPA) databases. GSE68465 was used to explore the relationship between the SPP1 expression and clinicopathological characteristics and the prognosis of LUAD patients. The relationship between SPP1 and immune infiltration in LUAD was analyzed by the Tumor Immune Estimation Resource (TIMER) database. Gene enrichment analysis was performed in GSEA. The Cancer Genome Atlas (TCGA)-LUAD data was used to verify the results.ResultsIn the cell line level, non-small cell lung cancer ranked ninth among cancer cell lines based on SPP1 expression. In the messenger RNA (mRNA) and protein levels, SPP1 expression was higher in LUAD tissues than that in normal control. SPP1 expression was related to gender, N stage, histological grade, and progression or relapse. In men, SPP1 expression were higher compared to that in women. The higher the N stage, the higher the SPP1 expression level. As LUAD progresses or relapses, SPP1 expression could increase. In the pathological grade, the SPP1 expression was higher in LUAD samples with moderate differentiation. In addition, the overall 5-year survival rates of the SPP1 high and low expression groups were 50.574 and 59.181% [P = 0.008; hazard ratio (HR) = 0.7057; 95% CI, 0.5467-0.9109], indicating that SPP1 had an impact on overall survival for LUAD patients. The relationship between SPP1 expression and CD4+ T cell, macrophage, neutrophil, and dendritic cell infiltration was weak in LUAD. SPP1 could be considered as an independent prognostic marker in LUAD (P = 0.003; HR = 1.150; 95% CI, 1.048-1.261) by multivariate Cox regression analysis. The results of GSEA indicated that samples with high SPP1 expression were enriched in protein secretion, mTORC1 signaling, angiogenesis, and glycolysis pathway. The analysis results obtained by TCGA-LUAD data were basically consistent with the results obtained by GSE68465.ConclusionsSPP1 can not only affect the occurrence and development of LUAD but also may be an independent prognostic marker of LUAD. SPP1 is expected to be a new target for molecular targeted therapy.
| S-EPMC7303289 | biostudies-literature
Project description:BACKGROUND:Mitochondrial dysfunction contributes to many types of human disorders and cancer progression. Inner membrane mitochondrial protein (IMMT) plays an important role in the maintenance of mitochondrial structure and function. The aims of this study were to examine IMMT expression in lung adenocarcinoma and evaluate its correlation with clinicopathological parameters and patient prognosis. METHODS:IMMT expression was immunohistochemically studied in 176 consecutive lung adenocarcinoma resection tissues, and its correlations with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox-proportional hazards models were used to estimate the effect of IMMT expression on survival. RESULTS:High-IMMT expression was detected in 84 of 176 (47.7%) lung adenocarcinomas. Levels were significantly correlated with advanced disease stage (stage II and III; P = 0.024), larger tumor size (>3 cm; P = 0.002), intratumoral vascular invasion (P < 0.001), and poorer adenocarcinoma patient prognosis (P = 0.002). Based on 176 patients with adenocarcinoma, multivariate analysis revealed that IMMT expression was an independent predictor of poorer survival (HR, 1.99; 95% confidence interval [CI], 1.06-3.74; P = 0.031). Further, treating A549 cells derived from lung adenocarcinoma, with IMMT siRNA resulted in significantly decreased proliferation. CONCLUSION:Here, we first demonstrated that high-IMMT expression is related to some clinicopathological parameters, and that its expression is an independent prognostic predictor of poorer survival in patients with lung adenocarcinoma; further studies are required to clarify the biological function of IMMT in lung adenocarcinoma. However, results suggest that this protein could be a novel prognostic indicator and therapeutic target.
| S-EPMC6825906 | biostudies-other
Project description:The cytochrome P450s (CYP450s) include key oxidative enzymes involved in the metabolism of various carcinogens and anticancer drugs. Bioinformatic studies have demonstrated the association of CYP3A43 with liver cancer and ovarian cancer. However, the biological function of CYP3A43 in tumor progression remains unclear. To further reveal the role of CYP3A43 in tumor progression, we first analyzed the data from the UALCAN database and found that CYP3A43 was negatively correlated to the cancer staging and lymph node metastasis of lung adenocarcinoma (LUAD). We established stable CYP3A43-knockdown LUAD H1299 cell line and found that its knockdown enhanced cell proliferation, colony formation, and migration in vitro, and promoted the growth of tumor xenograft in vivo. Interestingly, when CYP3A43 was ectopically-expressed in the LUAD cell lines, decreased cell proliferation and ERK1/2 phosphorylation level were observed. Lastly, we also identified CYP3A43 co-expressed genes in LUAD from LinkedOmics database followed by GO and KEGG analyses. In conclusion, our results indicate the unprecedented role of CYP3A43 in the suppression of LUAD and provide new possibilities for targeted therapy of this life-threatening disease.
| S-EPMC9820144 | biostudies-literature
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.
| S-EPMC4246704 | biostudies-literature
Project description:Several prognostic indicators have shown inconsistencies in patients of different genders with lung adenocarcinoma, indicating that these variations may be due to the different genetic background of males and females with lung adenocarcinoma. In this study, we first used the Gene-Cloud of Biotechnology Information (GCBI) bioinformatics platform to identify differentially expressed genes (DEGs) that eliminated gender differences between lung adenocarcinoma and normal lung tissues. Then, we screened out that transcription factor 21 (TCF21) is a hub gene among these DEGs by creating a gene co-expression network on the GCBI platform. Furthermore, we used the comprehensive survival analysis platforms Kaplan-Meier plotter and PrognoScan to assess the prognostic value of TCF21 expression in lung adenocarcinoma patients. Finally, we concluded that decreased mRNA expression of TCF21 is a predictor for poor prognosis in patients with lung adenocarcinoma.
| S-EPMC5435710 | biostudies-literature
Project description:Background:Fibroblast activation protein (FAP) is a type II cell surface-bound integral serine protease, which is an important biomarker of cancer-associated fibroblasts. FAP-? performs several biological activities, including remolding extracellular matrix and acting as an immunosuppressor in the tumor microenvironment. However, the proliferation role of FAP-? in human lung adenocarcinoma has not been fully elucidated. Methods:The expression of FAP-? in 94-paired human lung adenocarcinoma tissues was identified by immunohistochemistry test. The effect of FAP on cell proliferation was examined by CCK-8 assay. RNA-sequencing and bioinformatics analysis were utilized to investigate the underlying mechanism. Western blot analysis, quantitative polymerase chain reaction (qPCR), and nude mice experiments, were also conducted for further validation. Results:The proliferation rates of human fibroblast strains FAP-HFF and FAP-BJ, and human lung adenocarcinoma cell line FAP-SPC-A-1 were higher than those of controls. The nude mice experiment also showed that FAP could promote the proliferation of SPC-A-1 cell line in vivo. qPCR and Western blot analysis indicated that CCNB1 was upregulated by the overexpression of FAP in the lung adenocarcinoma cell line. The expression of FAP-? was higher in both the cytoplasm and stroma of lung adenocarcinoma than in adjacent normal tissues. Survival analysis indicated that patients with higher expression of FAP-? in tumor stroma had a poor prognosis (P=0.019). The Cancer Genome Atlas Program (TCGA) data also showed that the expression of FAP within tumor tissues was higher (in both cytoplasm and stroma) compared with that in normal tissues (P<0.05). Conclusions:Our study indicates that FAP-? could facilitate the proliferation of lung adenocarcinoma cells and can be a prognostic marker in human lung adenocarcinoma.
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Project description:Lymph node metastasis (LNM) is one of the major causes of cancer‑associated morbidity and mortality in patients with lung cancer following radical pulmonary carcinoma resection. The present study aimed to investigate the relationship between the expression of collagen and calcium‑binding epidermal growth factor domain‑containing protein 1 (CCBE1) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) in tumor tissue with the clinical prognosis of lung cancer. The present study included 40 patients with lung cancer that underwent pulmonary carcinoma resection, including 10 patients with LNM, and 10 control patients who underwent pulmonary bullae resection. CCBE1 and LYVE1 expression was assessed in samples from normal and tumor tissue using polymerase chain reaction, western blot analysis and immunohistochemistry. CCBE1 expression appeared to be decreased in lung tumor tissue and further downregulated in samples from patients with LNM, and was revealed to be correlated with poor clinical outcome. Conversely, LYVE1 expression appeared to be upregulated in lung cancer tissue. In conclusion, the present results suggested that CCBE1 and LYVE1 may have potential as biomarkers for the identification of lung cancer patients at a high risk of LNM.
| S-EPMC5783450 | biostudies-literature