Construction of the optimization prognostic model based on differentially expressed immune genes of lung adenocarcinoma

Abstract

Background Lung adenocarcinoma (LUAD) is the most common pathology subtype of lung cancer. In recent years, immunotherapy, targeted therapy and chemotherapeutics conferred a certain curative effects. However, the effect and prognosis of LUAD patients are different, and the efficacy of existing LUAD risk prediction models is unsatisfactory. Methods The Cancer Genome Atlas (TCGA) LUAD dataset was downloaded. The differentially expressed immune genes (DEIGs) were analyzed with edgeR and DESeq2. The prognostic DEIGs were identified by COX regression. Protein-protein interaction (PPI) network was inferred by STRING using prognostic DEIGs with p value< 0.05. The prognostic model based on DEIGs was established using Lasso regression. Immunohistochemistry was used to assess the expression of FERMT2, FKBP3, SMAD9, GATA2, and ITIH4 in 30 cases of LUAD tissues. Results In total,1654 DEIGs were identified, of which 436 genes were prognostic. Gene functional enrichment analysis indicated that the DEIGs were involved in inflammatory pathways. We constructed 4 models using DEIGs. Finally, model 4, which was constructed using the 436 DEIGs performed the best in prognostic predictions, the receiver operating characteristic curve (ROC) was 0.824 for 3 years, 0.838 for 5 years, 0.834 for 10 years. High levels of FERMT2, FKBP3 and low levels of SMAD9, GATA2, ITIH4 expression are related to the poor overall survival in LUAD (p < 0.05). The prognostic model based on DEIGs reflected infiltration by immune cells. Conclusions In our study, we built an optimal prognostic signature for LUAD using DEIGs and verified the expression of selected genes in LUAD. Our result suggests immune signature can be harnessed to obtain prognostic insights.

Penetrating Exploration of Prognostic Correlations of the FKBP Gene Family with Lung Adenocarcinoma

“…The combination of FKBP3 and HDAC2 was related to oxaliplatin resistance in colorectal cancer via the PTEN/AKT pathway [ 18 ]. Downregulation of FKBP3 suppressed breast cancer [ 81 ], and FKBP3 expression was associated with poor survival in LUAD [ 82 , 83 , 84 ]. Furthermore, FKBP4 was reported to be related to breast cancer [ 20 , 85 ], colorectal cancer [ 22 ], prostate cancer [ 86 ], and lung cancer [ 21 , 87 ].…”

Identification of a 6-RBP gene signature for a comprehensive analysis of glioma and ischemic stroke: Cognitive impairment and aging-related hypoxic stress

“…SMAD9 mutations have been reported in the progression of gastrointestinal ganglioma. In addition, a low expression of SMAD9 is related to a poor OS in lung adenocarcinoma (Ngeow et al, 2015 ; Zhai et al, 2021 ). The microtubule motor protein encoded by DYNC1H1 is involved in many cellular processes, such as mitosis and intracellular transport.…”

Proteomic alterations associated with residual disease in neoadjuvant chemotherapy treated ovarian cancer tissues

“…FERMT2 was upregulated in R1 versus R0 chemotherapy naïve tissues as well as in an independent cohort of HGSOC patients with (> 0.1 cm) versus without (no macroscopic) residual disease (n = 154), and that correlated with an increased risk of disease progression independent of patient age at diagnosis, residual disease status as well as disease stage. FERMT2, also known as Kindlin-2, has been associated with poor survival in lung adenocarcinoma [ 29 ] and hepatocellular carcinoma [ 30 ] and FERMT2 as well as other fermitin family members have been shown to promote EMT and metastasis through the ß catenin pathway [ 31 – 33 ]. In contrast, we observed increased abundance of MRI1 in pre-NACT tissue samples from R1 vs R0 patients and this protein was also correlated with a lower risk of disease progression.…”