A-kinase-interacting protein 1 overexpression correlates with deteriorative tumor features and worse survival profiles, and promotes cell proliferation but represses apoptosis in non-small-cell lung cancer.

BACKGROUND: This study aimed to explore the correlation of A-kinase-interacting protein 1 (AKIP1) expression with clinical characteristics as well as survival profiles in non-small-cell lung cancer (NSCLC) patients, and further investigate its underlying effect on regulating NSCLC cell functions. METHODS: 319 NSCLC patients who underwent resection were consecutively reviewed, and AKIP1 expression (in 319 tumor tissues and 145 adjacent tissues) was determined by immunohistochemistry. Disease-free survival (DFS) and overall survival (OS) were calculated. In vitro, control overexpression, AKIP1 overexpression, control shRNA and AKIP1 shRNA plasmids were transfected into A549 cells to evaluate the effect of AKIP1 on cell proliferation and apoptosis. RESULTS: A-kinase-interacting protein 1 expression was increased in tumor tissues compared to adjacent tissues, and it positively correlated with tumor size, lymph node metastasis and TNM stage in NSCLC patients. Kaplan-Meier curves displayed that AKIP1 high expression correlated with worse DFS and OS, and multivariate Cox's regression revealed that it was an independent predictive factor for poor survival profiles. In vitro experiments displayed that AKIP1 expression was elevated in PC9 and A549 cells compared to normal lung epithelial cells; moreover, cell proliferation was increased by AKIP1 upregulation but reduced by AKIP1 downregulation, and cell apoptosis was decreased by AKIP1 upregulation but increased by AKIP downregulation in A549 cells. Interestingly, AKIP1 promoted fibronectin and zinc finger E-box binding homeobox 1 expressions while reduced E-cadherin expression in A549 cells. CONCLUSION: A-kinase-interacting protein 1 overexpression correlates with deteriorative tumor features and worse survival profiles and promotes cell proliferation but represses apoptosis in NSCLC.

Correlation Between RASSF1A Gene Promoter Hypermethylation in Serum or Sputum and Non-Small Cell Lung Cancer (NSCLC): A Meta-Analysis.

BACKGROUND The aim of this study was to evaluate the efficacy of RASSF1A promoter hypermethylation of serum or sputum in diagnosis of non-small cell lung cancer (NSCLC) by pooling open published data. MATERIAL AND METHODS Open-published studies relevant to RASSF1A promoter hypermethylation and NSCLC diagnosis were screened through Medline, EMBASE, the Cochrane Library, Web of Science, Google Scholar, and CBM. Number of cases of true positive (tp), false positive (fp), false negative (fn), and true negative (tn) by RASSF1A gene promoter hypermethylation was extracted from each of the include original studies. The combined diagnostic sensitivity, specificity, and symmetric receiver operating characteristic curve (SROC) were calculated, as was the effect size. RESULTS Twelve studies with 826 NSCLC and 598 controls were included in the present work. The combined sensitivity and specificity were 0.45 (95%CI: 0.41-0.48) (random effects) and 0.99(95%CI: 0.98-1.00) (fixed effects) respectively. The pooled positive likelihood ratio (+LR) and negative likelihood ratio (-LR) were 20.27 (9.64-42.61) and 0.53 (0.42-0.66), respectively, through the random effects model. The combined DOR was 46.63 (95%CI: 17.30-125.65) through the fixed effects model. The AUC of the SROC was 0.9989, calculated through Moses's model for RASSF1A promoter hypermethylation as a biomarker in diagnosis of NSCLC. CONCLUSIONS The low diagnostic sensitivity for RASSF1A gene promoter hypermethylation indicated that it is not suitable for NSCLC screening. However, the high specificity made it effective for NSCLC confirmation diagnosis, which could be used instead of pathological diagnosis.