Identification of a TGF-ß signaling-related gene signature for prediction of immunotherapy and targeted therapy for lung adenocarcinoma.

BACKGROUND: Transforming growth factor (TGF)-ß signaling functions importantly in regulating tumor microenvironment (TME). This study developed a prognostic gene signature based on TGF-ß signaling-related genes for predicting clinical outcome of patients with lung adenocarcinoma (LUAD). METHODS: TGF-ß signaling-related genes came from The Molecular Signature Database (MSigDB). LUAD prognosis-related genes were screened from all the genes involved in TGF-ß signaling using least absolute shrinkage and selection operator (LASSO) Cox regression analysis and then used to establish a risk score model for LUAD. ESTIMATE and CIBERSORT analyzed infiltration of immune cells in TME. Immunotherapy response was analyzed by the TIDE algorithm. RESULTS: A LUAD prognostic 5-gene signature was developed based on 54 TGF-ß signaling-related genes. Prognosis of high-risk patients was significantly worse than low-risk patients. Both internal validation and external dataset validation confirmed a high precision of the risk model in predicting the clinical outcomes of LUAD patients. Multivariate Cox analysis demonstrated the model independence in OS prediction of LUAD. The risk model was significantly related to the infiltration of 9 kinds of immune cells, matrix, and immune components in TME. Low-risk patients tended to respond more actively to anti-PD-1 treatment, while high-risk patients were more sensitive to chemotherapy and targeted therapy. CONCLUSIONS: The 5-gene signature based on TGF-ß signaling-related genes showed potential for LUAD management.

High expression of RBM8A predicts poor patient prognosis and promotes tumor progression in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a huge threat for human health worldwide. As a complicated tumor, the molecular basis for HCC development especially metastasis requires exploration. Although RNA binding motif (RBM) proteins are closely related to various cancers, the clinical importance and underlying mechanisms of RBM8A in HCC remain elusive. In this study, we found that RBM8A was highly expressed in HCC tumor tissues compared to normal liver tissues. Overexpression of RBM8A was associated with HbsAg and Edmondson pathological grading. Moreover, Kaplan-Meier survival analysis showed that high expression of RBM8A was related to the poor overall survival and progression-free survival of patients with HCC. Gain- and loss-of-function experiments further demonstrated that RBM8A promoted tumor cell migration and invasion in HCC via activation of epithelial-mesenchymal transition signaling pathway. It is also noteworthy that RBM8A is required for tumor cell proliferation and anti-apoptosis in HCC. Altogether, our results revealed a close relationship between RBM8A and HCC prognosis as well as a critical tumor-promoting function of RBM8A in HCC progression, suggesting that RBM8A might be a potential bio-marker and drug target in HCC therapy.