Lung cancer is the third most frequently diagnosed cancer in the world, with lung adenocarcinoma (LUAD) as the most common pathological type. But studies on the predictive effect of a single gene on LUAD are limited. We aimed to discover new predictive markers for LUAD.

Epithelial-mesenchymal transition (EMT) process, which is regulated by genes of inducible factors and transcription factor family of signaling pathways, transforms epithelial cells into mesenchymal cells and is involved in tumor invasion and progression and increases tumor tolerance to clinical interventions. This study constructed a multigene marker for lung predicting the prognosis of lung adenocarcinoma (LUAD) patients by bioinformatic analysis based on EMT-related genes. Gene sets associated with EMT were downloaded from the EMT-gene database, and RNA-seq of LUAD and clinical information of patients were downloaded from the TCGA database. Differentially expressed genes were screened by difference analysis. Survival analysis was performed to identify genes associated with LUAD prognosis, and overlapping genes were taken for all the three. Prognosis-related genes were further determined by combining LASSO regression analysis for establishing a prediction signature, and the risk score equation for the prognostic model was established using multifactorial COX regression analysis to construct a survival prognostic model. The model accuracy was evaluated using subject working characteristic curves. According to the median value of risk score, samples were divided into a high-risk group and low-risk group to observe the correlation with the clinicopathological characteristics of patients. Combined with the results of one-way COX regression analysis, HGF, PTX3, and S100P were considered as independent predictors of LUAD prognosis. In lung cancer tissues, HGF and PTX3 expression was downregulated and S100P expression was upregulated. Kaplan-Meier, COX regression analysis showed that HGF, PTX3, and S100P were prognostic independent predictors of LUAD, and high expressions of all the three were all significantly associated with immune cell infiltration. The present study provided potential prognostic predictive biological markers for LUAD patients, and confirmed EMT as a key mechanism in LUAD progression.

Cancer is one of the main causes of human death worldwide. Recently, many studies have firmly established the causal relationship between oxidative stress and cancer initiation and progression. As a key protein in PI3K/Akt signaling pathway, p-AKT (phosphorylated Akt) participates in the process of oxidative stress and plays a prognostic role in various hematologic tumors and solid tumors. We conducted a comprehensive search of the PubMed, Embase and Cochrane libraries to identify studies published in the past decade involving cancer patients expressing p-AKT that reported overall survival (OS) during follow-up. In this study, 6,128 patients in total were evaluated from 29 enrolled articles, and we concluded that overexpression of p-AKT was closely related to worse OS in cancer patients with a hazard ratio (HR) of 2.33 (95% CI: 1.67-4.00). Furthermore, we conducted a subgroup analysis, and the results indicated that overexpression of p-AKT was associated with worse OS in hematological tumor (HR: 1.64, 95% CI: 1.41-1.92), and solid tumor (HR: 2.44, 95% CI: 1.61-5.26). High expression of p-AKT is related to poor prognosis of various hematologic tumors and solid tumors.

Epithelial-mesenchymal transition (EMT) bestows cancer cells with motile and invasive properties. But for ovarian tissues, EMT plays a physiological role in the postovulatory repair of ovary surface epithelial (OSE) cells. Accumulating data indicated that 1α,25(OH)2D3 decreased both the migration and invasion of various cancer cells by suppressing EMT. However, it remains unclear whether 1α,25(OH)2D3 inhibits the process of EMT during different stages of oncogenic transformation in mouse OSE (MOSE) cells. In present study, a spontaneous malignant transformation model of MOSE cells at three sequential stages (early, intermediate and late) was established in vitro first and then subjected to 1α,25(OH)2D3 treatment to investigate the effect of 1α,25(OH)2D3 on the oncogenic transformation of MOSE cells. We found that 1α,25(OH)2D3 significantly reduced the proliferation and invasion of late malignant transformed MOSE (M-L cells) cells by inhibiting EMT both in vitro and in vivo, but not in intermediate transformed (M-I) cells. Importantly, we found that the levels of CYP24A1 in M-I cells were dramatically higher than that in M-L cells following treatment with 1α,25(OH)2D3. Furthermore, we demonstrated that, in both M-I and M-L cells with CYP24A1 knockdown, 1α,25(OH)2D3 suppressed the proliferation and invasion, and reduced the expression of N-cadherin, Vimentin, β-catenin and Snail. In addition, knockdown of CYP24A1 suppressed EMT by increasing E-cadherin while decreasing N-cadherin, Vimentin, β-catenin and Snail. These findings provide support for inhibiting CYP24A1 as a potential approach to activate the vitamin D pathway in the prevention and therapy of ovarian cancer.