Systematic analysis of lncRNA gene characteristics based on PD-1 immune related pathway for the prediction of non-small cell lung cancer prognosis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is heterogeneous. Molecular subtyping based on the gene expression profiles is an effective technique for diagnosing and determining the prognosis of NSCLC patients. METHODS: Here, we downloaded the NSCLC expression profiles from The Cancer Genome Atlas and the Gene Expression Omnibus databases. ConsensusClusterPlus was used to derive the molecular subtypes based on long-chain noncoding RNA (lncRNA) associated with the PD-1-related pathway. The LIMMA package and least absolute shrinkage and selection operator (LASSO)-Cox analysis were used to construct the prognostic risk model. The nomogram was constructed to predict the clinical outcomes, followed by decision curve analysis (DCA) to validate the reliability of this nomogram. RESULTS: We discovered that PD-1 was strongly and positively linked to the T-cell receptor signaling pathway. Furthermore, we identified two NSCLC molecular subtypes yielding a significantly distinctive prognosis. Subsequently, we developed and validated the 13-lncRNA-based prognostic risk model in the four datasets with high AUC values. Patients with low-risk showed a better survival rate and were more sensitive to PD-1 treatment. Nomogram construction combined with DCA revealed that the risk score model could accurately predict the prognosis of NSCLC patients. CONCLUSIONS: This study demonstrated that lncRNAs engaged in the T-cell receptor signaling pathway played a significant role in the onset and development of NSCLC, and that they could influence the sensitivity to PD-1 treatment. In addition, the 13 lncRNA model was effective in assisting clinical treatment decision-making and prognosis evaluation.

Clinical implication of aquaporin 9 in non-small cell lung cancer patients: its expression and relationship with clinical features and prognosis.

BACKGROUND: Aquaporin 9 (AQP9) is recognized as a key regulator in several cancers, whereas little is known about its clinical implication in non-small cell lung cancer (NSCLC). Thus, we aimed to explore AQP9 expression and its relationship with clinical features, prognosis in NSCLC patients. METHODS: One hundred ninety-eight NSCLC patients who received resection were retrospectively enrolled. This study contained two cohorts: in cohort A, AQP9 protein expression (from formalin fixed paraffin embedded tumor and paired adjacent tissue specimens) in 198 patients was detected by immunohistochemistry (IHC). In cohort B, AQP9 mRNA expression (from fresh-frozen tumor and paired adjacent tissues) in 108 patients (out of 198 patients) was detected by RT-qPCR. RESULTS: In cohort A, increased AQP9 IHC score and greater proportion of AQP9 protein high expression cases were shown in tumor tissue than adjacent tissue (both P < 0.001). Tumor AQP9 protein high expression correlated with lymph node (LYN) metastasis (P = 0.002) and raised TNM stage (P = 0.012). Interestingly, tumor AQP9 protein high expression related to worse disease-free survival (DFS) (P = 0.002) and overall survival (OS) (P = 0.026). In cohort B, AQP9 mRNA expression in tumor tissue was increased than adjacent tissue (P < 0.001), and tumor AQP9 mRNA high expression linked to LYN metastasis (P = 0.024) and increased TNM stage (P = 0.032) as well; tumor AQP9 mRNA high expression was related to shorter DFS (P = 0.009), and it presented with a trend to be correlated with worse OS (P = 0.054), but without statistical significance. CONCLUSION: AQP9 serves as a potential indicator for monitoring disease progression and prognostication in NSCLC patients.