The oncogenic role of treacle ribosome biogenesis factor 1 (TCOF1) in human tumors: a pan-cancer analysis

Abstract

Treacle ribosome biogenesis factor 1 (TCOF1) plays a crucial role in multiple processes, including ribosome biogenesis, DNA damage response (DDR), mitotic regulation, and telomere integrity. However, its role in cancers remains unclear. We aimed to visualize the expression, prognostic, and mutational landscapes of TCOF1 across cancers and to explore its association with immune infiltration. In this work, we integrated information from TCGA and GEO to explore the differential expression and prognostic value of TCOF1. Then, the mutational profiles of TCOF1 in cancers were investigated. We further determined the correlation between TCOF1 and immune cell infiltration levels. Additionally, we determined correlations among certain immune checkpoints, microsatellite instability, tumor mutational burden (TMB), and TCOF1. Potential pathways of TCOF1 in tumorigenesis were analyzed as well. In general, tumor tissue had a higher expression level of TCOF1 than normal tissue. The prognostic value of TCOF1 was multifaceted, depending on type of cancer. TCOF1 was correlated with tumor purity, CD8+ T cells, CD4+ T cells, B cells, neutrophils, macrophages, and dendritic cells (DCs) in 6, 14, 16, 12, 20, 13, and 17 cancer types, respectively. TCOF1 might act on ATPase activity, microtubule binding, tubulin binding, and catalytic activity (on DNA), and participate in tumorigenesis through "cell cycle" and "cellular-senescence" pathways. TCOF1 could affect pan-cancer prognosis and was correlated with immune cell infiltration. "Cell cycle" and "cellular-senescence" pathways were involved in the functional mechanisms of TCOF1, a finding that awaits further experimental validation.

Treacle is Upregulated in Cancer and Correlates With Poor Prognosis

“…In summary, they suggest that upregulation of Treacle expression promotes carcinogenesis, stimulates proliferation, survival, and possibly contributes to radio-resistance, albeit with variation across different cancer types ( Figure 2 ). We observe significant upregulation of Treacle expression in 11 out of 14 different cancer types by analysis of paired normal and tumor data in agreement with other recently published studies ( Wu et al, 2021 ; Gu et al, 2022 ; Hu et al, 2022 ). Interestingly, in uterine corpus endometrial carcinoma, where Treacle expression was not increased, the highest frequency of TCOF1 mutations were identified by Gu et al, 2022 , possibly altering the properties of the expressed protein.…”

“…We observe significant upregulation of Treacle expression in 11 out of 14 different cancer types by analysis of paired normal and tumor data in agreement with other recently published studies ( Wu et al, 2021 ; Gu et al, 2022 ; Hu et al, 2022 ). Interestingly, in uterine corpus endometrial carcinoma, where Treacle expression was not increased, the highest frequency of TCOF1 mutations were identified by Gu et al, 2022 , possibly altering the properties of the expressed protein. Follow-up studies are needed to clarify if expression data accurately reflects protein levels and if Treacle is subjected to posttranslational modifications in cancer.…”

“…Wu et al demonstrated an inverse correlation between Treacle expression and CD8 + T cells, NK cells, and dendritic cells in HCC. A similar correlation between Treacle and immune infiltration by CD8 + T cells, CD4 + T cells, B cells, neutrophils, macrophages, and dendritic cells was also reported ( Gu et al, 2022 ). Both studies point to a possible cancer-promoting role of Treacle through inhibition of immune infiltration, supporting a broader role of Treacle in cancer progression than previously anticipated ( Figure 2 ).…”

“…An additional pan-cancer study by Gu et al analyzed expression levels from un-paired normal and tumor samples and prognostic value of Treacle. In this study, the authors found Treacle expression levels to be significantly upregulated in a broad range of cancers ( Gu et al, 2022 ). This study also correlated Treacle expression levels with patient outcome and found an overall correlation between high Treacle expression levels and poor survival in five cancer types.…”

Treacle Sticks the Nucleolar Responses to DNA Damage Together

“…Treacle upregulation is however emerging as a tumor promoting factor. Elevated Treacle levels correlated with poor prognosis, and shorter survival in different cancer types ( Gu et al, 2022 ; Hu et al, 2022 ; Wu et al, 2022 ). This could be attributed to Treacle’s function in facilitating rRNA transcription.…”