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Comprehensive pan-cancer analysis reveals the prognostic value and immunological role of SPIB.

ABSTRACT: It is well-established that SPIB is essential for the survival of mature B cells, playing a key role in diffuse large B-cell lymphoma, colorectal cancer, and lung cancer. However, no study has hitherto conducted a systematic pan-cancer analysis on SPIB. Herein, we analyzed the differential expression of SPIB in pan-cancer using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases and found that SPIB was significantly upregulated in most cancers. In addition, SPIB was positively or negatively associated with prognosis in different cancers. We found that SPIB was significantly associated with tumor immune infiltration and immune checkpoint genes in more than 35 tumors by TIMER database analysis. In addition, SPIB was negatively correlated with Tumor mutational burden (TMB) and Microsatellite instability (MSI) in most tumors. Finally, GO/KEGG enrichment analysis revealed the possible involvement of SPIB in NF-kappa B and B-cell receptor signaling pathways. In conclusion, our comprehensive pan-cancer analysis of SPIB reveals its important role in tumor immunity, suggesting it has huge prospects for clinical application in cancer therapy.

SUBMITTER: Ding M

PROVIDER: S-EPMC9417235 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Comprehensive pan-cancer analysis reveals the prognostic value and immunological role of SPIB.

Ding Meng M Li Qiufang Q Tan Xiao X Zhang Liangyua L Tan Jun J Zheng Lan L

Aging 20220814 15

It is well-established that SPIB is essential for the survival of mature B cells, playing a key role in diffuse large B-cell lymphoma, colorectal cancer, and lung cancer. However, no study has hitherto conducted a systematic pan-cancer analysis on SPIB. Herein, we analyzed the differential expression of SPIB in pan-cancer using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases and found that SPIB was significantly upregulated in most cancers. In addition, SPIB was po ...[more]

PMID: 35969172

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Project description:Background The TYMP gene encodes an important nucleoside metabolism enzyme which is a rate-limiting enzyme for chemotherapeutic drug metabolism. Previous studies have shown that TYMP is highly expressed in many different tumors, promoting invasiveness and progression, and that it helps to predict the response to chemotherapeutic drugs. However, the role of TYMP in tumor immunity and prognosis remains largely unclear. The purpose of this pan-cancer analysis was to acquire more data on the function of TYMP function and its clinical significance. Methods To access the TYMP expression, we accessed datasets from The Cancer Genome Atlas (TCGA), Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Cancer Cell Line Encyclopedia (CCLE) databases, and analyzed its differential expression between paired tumor and normal samples. We employed PrognoScan and Kaplan-Meier plotter for survival analyses. TYMP mutations were analyzed using cBioPortal. Correlations of TYMP with tumor stage, tumor mutational burden (TMB), microsatellite instability (MSI), immune checkpoint genes (ICGs), and immune cell infiltration were estimated via bioinformatics tools and methods. The CellMiner database was used to predict drug response. Gene set enrichment analysis (GSEA) was applied to explore the biological functions of TYMP in different tumors. Results Our results indicated that TYMP was overexpressed and also significantly associated with a worse prognosis in several human cancers, such as kidney clear cell carcinoma (KIRC) and lower grade glioma (LGG). TYMP was also associated with TMB, MSI, and ICGs across a variety of malignancies. TYMP was most significantly correlated with immune cell infiltration in five tumors, namely, breast cancer (BRCA), cervical cancer (CESC), KIRC, skin cutaneous melanoma (SKCM), and stomach adenocarcinoma (STAD). Moreover, TYMP expression predicted sensitivity to chemotherapy drugs and also influenced relevant biological pathways, according to enrichment analysis. Conclusions According to the results of this comprehensive analysis, TYMP is associated with prognosis and tumor immunology, which might make it be a potential therapeutic target for cancer treatment.

Project description:BackgroundThe spindle and kinetochore associated (SKA) complex, which plays important roles in proper chromosome segregation during mitosis by maintaining the stabilization of kinetochore-spindle microtubule attachment during mitosis, has recently been reported to exert regulatory effects on the initiation and progression of various human cancer types. Nevertheless, the prognostic significance and immune infiltration of the SKA family across cancers have not been well elucidated.MethodsUsing data from three large public datasets, including The Cancer Genome Atlas, Genotype-Tissue Expression, and Gene Expression Omnibus databases, a novel scoring system (termed the SKA score) was developed to quantify the SKA family level across cancers. We then evaluated the prognostic impact of the SKA score on survival and assessed the effect of the SKA score on immunotherapy at the pan-cancer level using multiomics bioinformatic analyses. The correlation of the SKA score and the tumor microenvironment (TME) was also explored in depth. Potential small molecular compounds and chemotherapeutic agents were assessed by CTRP and GDSC analyses. Immunohistochemistry was performed to verify the expression of the SKA family genes.ResultsOur results demonstrated a close correlation between the SKA score and tumor development and prognosis in multiple cancers. The SKA score was positively related to cell cycle pathways and DNA replication across cancers, such as E2F targets, the G2M checkpoint, MYC targets V1/V2, mitotic spindles and DNA repair. Additionally, the SKA score was negatively related to the infiltration of various immune cells with antitumor effects in the TME. In addition, the potential value of the SKA score was identified to predict immunotherapy response for melanoma and bladder cancer. We also demonstrated a correlation between SKA1/2/3 and the response to drug treatment across cancers and the promising potential of the SKA complex and its genes as therapeutic targets in cancer. Immunohistochemistry demonstrated that the expression differences of SKA1/2/3 were significant between the breast cancer group and the paracancerous group.ConclusionThe SKA score plays a critical role in 33 cancer types and is highly related to tumor prognosis. Patients with elevated SKA scores have a clear immunosuppressive TME. The SKA score may serve as a predictor for patients receiving anti-PD-1/L1 therapy.

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Comprehensive pan-cancer analysis reveals the prognostic value and immunological role of SPIB.

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Comprehensive pan-cancer analysis reveals the prognostic value and immunological role of SPIB.

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