發(fā)布者：抗性基因網(wǎng) 時(shí)間：2023-06-12 瀏覽量：382
摘要
出身背景
腫瘤微環(huán)境以血管生成為特征。腫瘤的微環(huán)境（TME）及其與免疫療法的相互作用影響免疫療法的有效性。在肺腺癌（LUAD）的研究中，目前多種血管生成基因與臨床結(jié)果、免疫細(xì)胞浸潤和免疫治療之間沒有明確的聯(lián)系。
方法
從GEO和TCGA下載臨床信息和相應(yīng)的基因表達(dá)。對(duì)36個(gè)血管生成相關(guān)基因（ARGs）進(jìn)行了綜合評(píng)估，以及血管生成與轉(zhuǎn)錄模式和預(yù)后之間的相關(guān)性。免疫差異在亞群中表現(xiàn)出不同的功能和浸潤。KEGG通路和GO富集分析是基于不同的聚類進(jìn)行的。建立ARG_score以量化每個(gè)患者的血管生成亞型。最后，我們?cè)u(píng)估了它們?cè)陬A(yù)測(cè)不同風(fēng)險(xiǎn)組的預(yù)后和治療反應(yīng)方面的價(jià)值。
后果
在遺傳水平上討論了LUAD標(biāo)本中ARGs的突變。我們確定了兩種不同的分子亞型，并觀察到ARG突變與患者的臨床特征、預(yù)后和TME有關(guān)。接下來建立預(yù)測(cè)總生存期（OS）的ARG_，
證實(shí)了其對(duì)LUAD患者的強(qiáng)大預(yù)測(cè)能力。此外，還創(chuàng)建了一個(gè)高度可靠的諾模圖。低風(fēng)險(xiǎn)評(píng)分表明操作系統(tǒng)更好。此外，ARG核心與癌癥干細(xì)胞指數(shù)和藥物敏感性顯著相關(guān)。FSTL3被認(rèn)為是潛在的靶基因。
結(jié)論
總的來說，我們是第一個(gè)描述LUAD患者ARGs預(yù)后的人。血管生成可能在LUAD的發(fā)展中發(fā)揮重要作用。這一特征可能有助于闡明TME中血管生成的特征，并有助于探索更具成本效益的免疫治療策略。
Abstract
Background
Tumor microenvironment is characterized by angiogenesis. A tumor's microenvironment (TME) and its interactions with immunotherapy influence
immunotherapy's effectiveness. In the study of Lung adenocarcinoma (LUAD), there is currently no clear link between multiple angiogenesis genes and clinical
results, immune cell infiltration, and immunotherapy.
Methods
Clinical information and corresponding Gene expression were downloaded from the GEO and TCGA. Thirty-six angiogenesis-related genes (ARGs) were
comprehensively evaluated, and correlations between angiogenesis and patterns of transcription and prognosis. The immune difference shows different
functions and Infiltration in the sub-cluster. KEGG pathway and GO enrichment analyses were conducted based on distinct clusters. ARG_score was
established to quantify the angiogenic subtype of each patient. Finally, we assessed their value in predicting prognosis and treatment response in the different
risk groups.
Results
The mutations of ARGs in LUAD specimens were discussed at the genetic level. We identified two distinct molecular subtypes and observed that ARG
mutations were associated with clinical characteristics, prognosis, and TME of patients. Next, an ARG_score predicting overall survival (OS) was established,
confirming its robust predictive power for patients with LUAD. Moreover, a highly reliable Nomogram was created. Low risk score demonstrated better OS. In
addition, the ARG_score was shown to be significantly correlated with cancer stem cell index and drug sensitivity. FSTL3 is considered potential target gene.
Conclusion
In general, we were the first to characterize the prognosis of ARGs in patients with LUAD. Angiogenesis may play an essential role in the development of LUAD.
This characterization may assist in clarifying the features of angiogenesis in TME and enable the exploration of more cost-effective immunotherapy
strategies.
https://assets.researchsquare.com/files/rs-2417491/v1/e46c64c7-e54f-42cc-a5a5-c3579c7887e7.pdf?c=1673036461