Identification of a chemotherapy-associated gene signature for a risk model of prognosis in gastric adenocarcinoma through bioinformatics analysis.

Background: Over the past few years, the overall survival rate of patients with gastric adenocarcinoma who have received different chemotherapy regimens has increased. However, not all gastric cancer patients who receive chemotherapy have a longer survival. We need better predictive biomarkers. This study is to construct a new risk model of chemotherapy-associated genes in gastric adenocarcinoma (GA) for prognostication. Methods: RNA-seq data and clinical information of GSE26901 (containing 44 chemotherapy samples and 65 patients without chemotherapy) in Gene Expression Omnibus (GEO) and stomach adenocarcinoma (STAD, containing 360 cancer tissue samples and 50 paired normal tissue samples) in The Cancer Genome Atlas (TCGA) were selected for screening differentially expressed genes (DEGs). Multivariate Cox regression was conducted to screen prognosis-associated genes and its link to patients' prognosis were screened by least absolute shrinkage and selection operator (LASSO) regression analysis. Based on the key genes, a risk scoring equation for the prognosis model was established, and constructed survival prognosis model. The model was tested for predictive ability through training set (TCGA datasets) and validation set (GSE84437). The correlations of the risk score with clinical pathological features, immune score and drug sensitivity score were evaluated. Results: In total, 179 overlapping genes were obtained by screening DEGs. Univariate Cox analysis revealed 36 prognosis-related genes, and LASSO regression analysis revealed 8 key genes (KCNJ2, GATA5, CLDN1, SERPINE1, FCER2, PMEPA1, TMEM37 and CRTAC1). Kaplan-Meier (K-M) analysis uncovered a relatively short overall survival time in the high-risk group. The model was verified to possess favourable predictive ability. In addition, the nomogram model were demonstrated good predictability with area under the curve (AUC) for 1-5 years in training set were 0.78, 0.78, 0.76, 0.79 and 0.81. The high-risk group was less likely to get benefits from immunotherapy and less sensitive to cisplatin. Conclusions: According to the results of our training set and validation set, the risk model based on the eight chemotherapy-related gene signatures predicting prognosis has certain predictive accuracy in predicting the survival of GA patients which can be a promising prognostic parameter for GA. However, its efficacy remains to be proved in clinical practice.

Tumor suppressor role of hsa_circ_0035445 in gastric cancer.

Circular RNAs (circRNAs) are closely related to the occurrence and development of cancers. However, the roles of circRNAs in gastric cancer are largely unknown. Total 104 pairs of gastric cancer tissues and non-cancer tissues, fasting plasma of 42 healthy people and 42 gastric cancer patients' one day before operation and 10 days after operation were collected. Quantitative reverse transcription-polymerase chain reaction was used to detect the expression level of hsa_circ_0035445. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to analyze its diagnostic value. Small interfering RNA and overexpression vector were used to downregulate and upregulate the expression of hsa_circ_0035445, respectively. Cell Counting Kit-8 and colony formation assays were used to detect the proliferation ability. Trans-well assay and scratch assay were used to detect the migration ability. Finally, flow cytometry was used to detect the changes of cell cycle distribution and apoptosis. Hsa_circ_0035445 was lowly expressed in gastric cancer tissues, plasma of gastric cancer patients, and gastric cancer cells. The expression level of hsa_circ_0035445 in gastric cancer tissues was relationship with tumor size and distant metastasis. The AUC of hsa_circ_0035445 in tissues and plasma was 0.68 and 0.86, respectively. Upregulation of hsa_circ_0035445 suppressed the proliferation and migration, promoted apoptosis, and blocked cells at G0/G1 phase. Downregulation of hsa_circ_0035445 promoted the proliferation and migration, suppressed apoptosis, and blocked cells at S phase. In conclusion, hsa_circ_0035445 may become a new target for the treatment of gastric cancer.

Upregulation of miR-324-5p Inhibits Proliferation and Invasion of Colorectal Cancer Cells by Targeting ELAVL1.

Colorectal cancer (CRC) is a common clinical cancer that remains incurable in most cases. miRNAs are reported to play a part in the development of various tumors. In the present study, we found that miR-324-5p was downregulated in CRC cells, while ELAV (embryonic lethal, abnormal vision, Drosophila)-like protein 1 (ELAVL1) showed a higher expression. miR-324-5p transfection significantly inhibited the proliferation as well as invasion in both SW620 and SW480 cells. miR-324-5p mimic transfection markedly decreased the expression of ELAVL1. Luciferase reporter gene assay confirmed that ELAVL1 is a direct target of miR-324-5p. Furthermore, cancer invasion factors uPA, uPAR, and MMP-9 were found to drop significantly in miR-324-5p-transfected groups. To conclude, our findings indicate that miR-324-5p may play a suppressive role in colorectal cell viability and invasion, at least in part, through directly targeting ELAVL1. Therefore, miR-234-5p might function as a promising candidate for CRC treatment and deserves deeper research.

Significance of estrogen receptor subtypes in breast tumorigenesis and progression.

The aim of the study was to investigate the effects of estrogen receptor (ER) subtypes (ERα and ERß) on breast cancer development and progression. The expression level of ERα and ERß in breast cancer tissues and paired normal breast tissues were detected by Western blot analysis and immunohistochemistry (IHC) staining. The features of ERα and ERß status in cancer tissues or normal breast tissues and the correlations between clinicopathological characteristics and prognosis were analyzed. The expression levels of ERα and ERß in breast cancer tissues are significantly lower than those in the paired normal tissues. The expression of ERß is decreased more than that of ERα. ERα expression levels in cancer tissues are associated with tumor diameter, tumor-node-metastasis (TNM) stage, and progesterone receptor (PR) status. However, ERß expression levels in cancer tissues are not correlated with clinicopathological factors of patients with breast cancer. In conclusion, ER subtypes might play different roles in the development of breast cancer.