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To explore the expression of thrombospondin-1 (THBS1) in pan-cancer and its relevance to tumor microenvironment (TME).
The discrepancies in the expression and prognostic significance of THBS1 were examined in 33 different types of tumors using TCGA and GTEx data. The correlation between THBS1 and the TME index, various factors like immune cell infiltration, tumor mutagenesis burden (TMB) and microsatellite instability(MSI) was evaluated using computational methods. The potential mechanism was also dissected by constructing interaction networks of THBS1 with other genes by GEPIA; this was validated using multiplex immunohistochemistry(mIHC) in pancreatic cancer (PAAD) tissues.
Pan-cancer analysis revealed THBS1 mRNA was differentially expressed in 17 common cancer types (all P<0.05) and differential expression of the THBS1 protein was observed in 9 cancer types (all P<0.001). Survival analysis indicated that higher THBS1 expression was significantly associated with poorer patient prognosis in various malignant tumors (P<0.05). THBS1 expression was statistically significantly correlated with cancer-associated fibroblast (CAFs) infiltration across all cancer types (P<0.05), and positively associated with the expression of multiple immune checkpoint genes, including CD274(P<0.001)、HAVCR2(P<0.001)、PDCD1LG2(P<0.001)、LAG3(P<0.001)、PDCD1(P<0.001)、CTLA4(P<0.001) and TIGIT(P<0.001). These findings suggested that THBS1 may contribute to reduced responsiveness to immunotherapy by shaping an immunosuppressive tumor microenvironment. Co-expression and enrichment analyses demonstrated that the integrin genes strongly correlated with THBS1 in pancreatic adenocarcinoma (PAAD) were ITGAV (r=0.60, P<0.001)、ITGB3 (r=0.54, P<0.001) and ITGB1 (r=0.69, P<0.001). These findings were validated in pancreatic cancer tissues: immunofluorescence co-localization analysis demonstrated a strong positive correlation between THBS1 expression and integrin ITGAV (r=0.75, P<0.001).
This study identifies THBS1 as a crucial pan-cancer prognostic biomarker and a key regulator of the TME, providing a compelling rationale for its potential as a therapeutic target in oncology.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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