Objective To evaluate the correlation between cyclin B1 (CCNB1) gene expression and the prognosis of lung adenocarcinoma. Methods Oncomine, STRING, Human Protein Atlas, The Cancer Genome Atlas and other databases as well as Kaplan-Meier method, Cox regression, receiver operating characteristic (ROC) curve and Spearman correlation analysis were used to verify the effect of CCNB1 on patients with lung adenocarcinoma. Results CCNB1 was highly expressed in lung adenocarcinoma, and the high expression was correlated with T stage (P=0.001), N stage (P<0.001), pathological stage (P<0.001) and gender (P=0.008). Univariate Cox regression analysis showed that the expression of CCNB1, T stage, N stage, M stage and pathological stage were the factors affecting the overall survival rate of patients with lung adenocarcinoma (P<0.05); multivariate Cox regression analysis showed that the expression of CCNB1 and T stage were independent risk factors for overall survival of patients with lung adenocarcinoma (P<0.05). Kaplan-Meier analysis showed that high expression of CCNB1 was associated with shorter overall survival [hazard ratio (HR)=1.60, 95% confidence interval (CI) (1.20, 2.14), P=0.002], disease-specific survival [HR=1.68, 95%CI (1.16, 2.44), P=0.006] and progression-free interval [HR=1.42, 95%CI (1.09, 1.85), P=0.009]. The ROC curve showed that CCNB1 might be a potential diagnostic molecule for lung adenocarcinoma [area under the curve=0.980, 95%CI (0.967, 0.993)]. Spearman correlation analysis showed that CCNB1 expression was positively correlated with the infiltration of T helper cells 2 (rs=0.805, P<0.001) and T helper cells (rs=0.103, P=0.017), and negatively correlated with the infiltration of natural killer cells (rs=?0.195, P<0.001), macrophages (rs=?0.134, P=0.002), and T cells (rs=?0.092, P=0.033). Conclusion CCNB1 is highly expressed in lung adenocarcinoma compared with normal tissues, which is related to poor prognosis and may provide a potential therapeutic target for patients with lung adenocarcinoma.
ObjectiveTo explore the interaction between immune cell infiltration and extracellular matrix (ECM) in diffuse gastric cancer (DGC), and to identify novel diagnostic biomarkers and therapeutic targets. MethodsTranscriptomic data of DGC patients from The Cancer Genome Atlas (TCGA) database were analyzed to screen potential regulator factor of immune-related and ECM receptor-related signaling pathways. Differential expression of the identified regulator was assessed between the DGC tissues and the adjacent gastric tissues. Bioinformatics analysis was utilized to evaluate the relation between the regulator factor and immune cell infiltration and ECM, as well as prognosis. The clinical validation was performed using 90 paraffin-embedded DGC tissues and adjacent gastric tissues from the patients treated at The Lanzhou University Second Hospital (hereafter “our hospital”) from January 2017 to December 2019. The immunohistochemical staining was employed to examine the expression of regulator factor, followed by analysis of its association with immune cell infiltration, clinicopathologic features, and prognosis. Additionally, 10 paired DGC tissues and adjacent gastric tissues from the patients treated in our hospital in 2024 were collected for validation using real-time quantitative PCR to assess mRNA expression. The significance level was set at α=0.05. ResultsThe collagen type I alpha 1 chain (COL1A1), a potential regulator factor linked to immune and ECM receptor signaling pathways, was identified from the TCGA database. The COL1A1 was significantly overexpressed in the DGC tissues compared to the adjacent gastric tissues (P<0.001), and its high expression correlated with poorer prognosis [HR(95%CI)=2.98(1.21, 7.30), P=0.017]. The COL1A1 gene expression negatively correlated with CD8+ T cell enrichment score (CIBERSORT: r=?0.17, P<0.001; xCELL: r=?0.32, P<0.001) but positively correlated with M2 tumor-associated macrophage enrichment score (CIBERSORT: r=0.32, P<0.001; xCELL: r=0.24, P<0.001). The clinical validation confirmed that the COL1A1 protein and mRNA were both overexpressed in the DGC tissues (P<0.001). The patients with high COL1A1 protein expression had worse overall survival (P<0.001), and high expression (vs. low) was an independent risk factor for postoperative overall survival [HR(95%CI)=6.607(3.374, 12.940), P<0.001]. The COL1A1 protein expression positively correlated with CD163 (an M2 macrophage marker; r=0.76, P<0.001) and negatively with CD8+ (T cell marker, r=?0.84, P<0.001). ConclusionThis study demonstrates that COL1A1 is a potential therapeutic target for immune suppression and ECM interaction in DGC and a critical prognostic factor for long-term survival in patients with DGC.
Objective To investigate the expression of TNFAIP8L2 gene in lung adenocarcinoma (LUAD), its correlation with clinical characteristics, and its functional role as a potential tumor suppressor using a combination of bioinformatics approaches and in vitro experiments. MethodsThe differential expression of TNFAIP8L2 between LUAD tissues and normal lung tissues were analyzed using UALCAN and TIMER databases, followed by further association analyses to elucidate the relationship between TNFAIP8L2 expression and clinical features in LUAD patients. Forty-eight pairs of LUAD and adjacent normal lung tissue samples were collected and subjected to quantitative real-time polymerase chain reaction (qRT-PCR) to validate the expression level of TNFAIP8L2. In vitro, the effects of TNFAIP8L2 overexpression on proliferation and metastasis were assessed using CCK8 and transwell assays in A549 cells. The GEPIA and TIMER databases were utilized to explore the correlation between TNFAIP8L2 expression and patient prognosis. Moreover, STRING, cBioportal, and TISIDB databases were consulted to delve into potential protein-protein interactions involving TNFAIP8L2, its mutational status, and its relevance to immune cell infiltration within the tumor microenvironment of LUAD. ResultsTNFAIP8L2 expression was significantly lower in LUAD tissues compared to normal lung tissues, and low TNFAIP8L2 expression was strongly associated with poorer prognosis in LUAD patients. In vitro experiments definitively demonstrated that increased expression of TNFAIP8L2 could effectively inhibit proliferation and migration of A549 cells. TNFAIP8L2 was found to potentially interact with specific proteins including TLR1, CASP8, RAC1, SASH3, ARHGAP9, GIMAP8, S1PR4, LST1, TES, and RGS18. Additionally, TNFAIP8L2 expression was correlated with the infiltration levels of immune cells, such as NK cells, CD4+ and CD8+ T lymphocytes and others. ConclusionTNFAIP8L2 displays a trend of low expression in LUAD, where its downregulation is indicative of an adverse prognosis. Overexpression of TNFAIP8L2 effectively suppresses the growth and metastasis of LUAD cells. TNFAIP8L2 emerges as a promising biomarker with potential applications in LUAD diagnosis, prognosis evaluation, and guiding the development of immunotherapeutic strategies.