膠質母細胞瘤早期復發和假性進展的癌癥免疫差異表達基因分析及活性化合物預測

【摘要】 目的 對早期復發和假性進展膠質母細胞瘤的癌癥免疫差異基因進行研究分析并預測活性化合物。方法 在高通量基因表達（GEO）數據庫中選擇GSE231994數據集作為主要分析對象，篩選二次手術后早期復發和假性進展病例樣本之間的免疫相關差異基因，進行基因本體論（GO）生物過程（BP）和京都基因與基因組百科全書（KEGG）分析，構建蛋白質-蛋白質相互作用（PPI）網絡，獲得樞紐基因。應用TCMSP計算系統生物學實驗室平臺數據庫預測可能有效的活性化合物，并在CB-Dock2服務器進行分子對接實驗。結果GSE231994數據集篩選得到140差異表達基因，其中上調基因50個，下調基因90個，其中核心基因有IL1B、IL10、CXCL8、EGFR、TLR2、CD68、CXCR4、ITGB2、CD163和CSF1R，主要參與炎癥反應、信號轉導和免疫反應生物過程，以及富集于癌癥途徑、細胞因子-細胞因子受體相互作用和PI3K/Akt信號通路。根據度值選取前三個基因，通過TCMSP平臺預測得到槲皮素可能為有效化合物。對接結果顯示槲皮素與IL1B具有更好的結合能力。結論 通過生物信息手段分析揭示免疫表達基因IL1B、IL10和CXCL8與膠質母細胞瘤早期復發和假性進展有著密切的關系，而槲皮素可作為干預的有效活性化合物。

【關鍵詞】 早期復發；假性進展；膠質母細胞瘤；生物信息學；差異基因

【中圖分類號】 R739.41" 【文獻標志碼】 A" 【文章編號】 1672-7770（2025）01-0039-08

Analysis of cancer-immune differentially expressed genes and prediction of active compounds in progression and pseudo-progression of glioblastoma

Abstract： Objective To study and analyze cancer-immune differentially expressed genes in progression and pseudo-progression glioblastoma， and predict active compounds. Methods The GSE231994 dataset was selected as the main analysis dataset in the Gene Expression Omnibus（GEO） database， and immune related differentially expressed genes were screened between samples of progression and pseudo-progression cases after secondary surgery. Biological Process（BP） of Gene Ontology（GO）， and Kyoto Encyclopedia of Genes and Genomes（KEGG） analyses were performed to construct a protein-protein interaction（PPI） network and obtain hub genes. The TCMSP platform was applied to predict potentially active compounds， and molecular docking was accomplished on the CB Dock2 server. Results One hundred and forty differentially expressed genes were screened from the GSE231994 dataset， including 50 up-regulated genes and 90 down-regulated genes. The core genes included IL1B， IL10， CXCL8， EGFR， TLR， CD68， CXCR4， ITGB， CD16， and CSF1R， which mainly participated in inflammatory response， signal transduction， and immune response biological processes， as well as were enriched in the cancer pathway， cytokine-cytokine receptor interaction， and PI3K/Akt signaling pathways. The top three genes based on degree values were selected to predict， and quercetin may be an bio-active compound. The molecular docking results showed that quercetin had better binding ability with"IL1B. Conclusions It is revealed that immune expression genes IL1B， IL10， and CXCL8 are closely related to progression and pseudo-progression of glioblastoma， and quercetin can serve as an effective active compound for intervention via bioinformatics analysis.

Key words： progression; pseudo-progression; glioblastoma; bioinformatic; differentially expressed gene

膠質瘤是最常見的顱內腫瘤之一，其中膠質母細胞瘤（glioblastoma，GBM）是最為常見的惡性腦膠質瘤類型，預后極差，綜合治療后中位生存期也只有12～15個月［1］。GBM最常見的治療方法是手術治療，但手術切除后很容易復發。……