Prognostic biomarker TUBA1C is correlated to immune cell infiltration in the tumor microenvironment of lung adenocarcinoma

Abstract

Background TUBA1C is a microtubule component that is involved in a variety of cancers. Our main objective was to investigate TUBA1C expression, its prognostic value, its potential biological functions, and its impact on the immune system of patients with lung adenocarcinoma (LUAD). Methods The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA) and Immunohistochemistry Analysis were used to analyze TUBA1C expression, its clinicopathology, overall survival (OS), and disease-free survival (DFS) in LUAD patients. We also determined the correlation between TUBA1C and tumor-infiltrating immune cells (TIICs) by using CIBERSORT and GEPIA databases. To determine the expression of TUBA1C in LUAD, we analyzed a collection of immune infiltration levels and cumulative survival of LUAD tissues in TIMER database. By using UALCAN, STRING, and GeneMANIA databases, we investigated the protein-coding genes related to TUBA1C and its co-expression genes in LUAD tissues. Gene set enrichment analysis (GSEA) was performed by using the TCGA dataset. Results The mRNA and the protein expression of TUBA1C were found to be up-regulated in LUAD tissues. The univariate analysis indicated that an increased expression of TUBA1C was significantly correlated to the following parameters: age, stage, and lymph node metastasis. An over-expression of TUBA1C was associated with a poor prognosis of LUAD. In TIMER and CIBERSORT databases, we found that TUBA1C is correlated with 13 types of TIICs: activated B cell, activated CD4 T cell, central memory CD4 T cell, effector memory CD8 T cell, eosinophils, immature B cell, gamma-delta T cell, immature dendritic cell, mast cell, memory B cell, natural killer T cell, regulatory T cell, and type 2T helper cell. By performing GSEA, we found that TUBA1C is closely correlated to cell cycle, p53 signaling pathway, glycolysis, and gluconeogenesis. Conclusions Our findings indicate that TUBA1C is associated with TIICs in tumor microenvironment. Therefore, it serves as a novel prognostic biomarker and a target for future treatment methods of LUAD.

TUBA1C is a Prognostic Marker in Low-grade Glioma and Correlates with Immune Cell Infiltration in the Tumor Microenvironment

“…Moreover, TUBA1C had different correlations with different immune cell subtypes, such as macrophages M0, M1, M2 (Figures 4J-L). Similarly, a previous study has illustrated that TUBA1C relates to the tumorinfiltrating cells of lung adenocarcinoma (Bian et al, 2021). We also demonstrated that TUBA1C was co-expressed with multiple immune-related genes, such as particular MHC genes, immune activation genes, immunosuppresive genes, chemokine receptor related genes, and chemokine related genes (Figures 5A-E).…”

“…It has been reported that TUBA1C, a multifunctional cytoskeleton protein, is a kind of α-tubulin subtype and that it is correlated with microtubules, participating in the progress of cellular mitosis and division ( Jordan and Wilson, 2004 ; Albahde et al, 2020 ). It has been revealed that high the expression of TUBA1C predicts a poor prognosis of hepatocellular carcinoma ( Wang et al, 2017 ), lung adenocarcinoma ( Bian et al, 2021 ), breast cancer ( Wang et al, 2019 ), and osteosarcomas ( Li et al, 2010 ). However, the role of TUBA1C in LGG and whether TUBA1C has immune-related biological functions in LGG have not been reported.…”

“…Additionally, α-tubulin is involved in the occurrence of astrocytoma and chemoresistance in hepatocellular carcinoma (HCC) which greatly affects the prognosis of patients with liver cancer ( Tsai et al, 2014 ; Hu et al, 2021 ). Notably, overexpression of TUBA1C, which is one of the α-tubulin subtypes is involved in the poor prognosis of HCC ( Li et al, 2017 ), pancreatic ductal adenocarcinoma ( Albahde et al, 2020 ), and lung cancer ( Bian et al, 2021 ). However, whether TUBA1C can affect the prognosis of LGG has not been explored.…”

“…In addition, genes associated with immune components of the TME are of great value as prognostic biomarkers ( Le Rhun et al, 2019 ). Recently, several studies have proposed that TUBA1C is related to poor prognosis in HCC ( Wang et al, 2017 ), pancreatic ductal adenocarcinoma ( Albahde et al, 2020 ), and lung adenocarcinoma ( Bian et al, 2021 ). However, no studies have yet explored whether TUBA1C overexpression affects the tumor immune microenvironment of LGG.…”

Mutation of the EPHA2 Tyrosine-Kinase Domain Dysregulates Cell Pattern Formation and Cytoskeletal Gene Expression in the Lens

“…Among the most upregulated genes (>4-fold) in both Epha2-Q722 and Epha2-indel722 mutant lenses were those for tubulin alpha 1C (TUBA1C) and alkaline ceramidase-2 (ACER2). TUBA1C serves as a prognostic biomarker for a variety of cancers [64] and ACER2 is a Golgi enzyme involved in regulating B1 integrin maturation and cell adhesion [65]. In Epha2-Q722 and Epha2-null lenses, the gene for steroidogenic acute regulatory protein-related lipid transfer (START) domaincontaining protein 9 (STARD9) was strongly upregulated, whereas that for doublecortin domain-containing 2a (DCDC2a) was strongly upregulated in Epha2-indel722 and Epha2null lenses.…”