【佳學(xué)基因檢測(cè)】基于深度學(xué)習(xí)的肺癌鐵死亡相關(guān)基因特征的臨床和生物學(xué)意義

腫瘤基因檢測(cè)龍頭企業(yè)國(guó)產(chǎn)

在高峰論壇中體會(huì)到《Comput Math Methods Med》在.?2022 Aug 25;2022:6495301.發(fā)表了一篇題目為《基于深度學(xué)習(xí)的肺癌鐵死亡相關(guān)基因特征的臨床和生物學(xué)意義》腫瘤靶向藥物治療基因檢測(cè)臨床研究文章。該研究由Xiaosong Yang,?Xuanjian Hu,?Na Guo等完成。促進(jìn)了腫瘤的正確治療與個(gè)性化用藥的發(fā)展，進(jìn)一步強(qiáng)調(diào)了基因信息檢測(cè)與分析的重要性。

腫瘤靶向藥物及正確治療臨床研究?jī)?nèi)容關(guān)鍵詞：

腫瘤靶向治療基因檢測(cè)臨床應(yīng)用結(jié)果

?；o酶A合成酶長(zhǎng)鏈家族成員4（ACSL4）與腫瘤的發(fā)生有關(guān)，并與鐵死亡過(guò)程有關(guān)。深度學(xué)習(xí)已應(yīng)用于醫(yī)療保健的許多領(lǐng)域，包括影像診斷、數(shù)字病理學(xué)、癌癥分類(lèi)和轉(zhuǎn)移預(yù)測(cè)。盡管如此，ACSL4 的表達(dá)水平及其在非小細(xì)胞肺癌 (NSCLC) 中的預(yù)測(cè)意義目前尚不清楚。在 Oncomine 和 TCGA 數(shù)據(jù)庫(kù)的幫助下，預(yù)測(cè)了 NSCLC 中的 ACSL4 mRNA 表達(dá)及其與 NSCLC 預(yù)后的聯(lián)系。通過(guò)進(jìn)行實(shí)時(shí) PCR，我們檢測(cè)了人類(lèi) NSCLC 樣本中存在的 ACSL4 表達(dá)水平。使用 Kaplan-Meier 曲線(xiàn)分析了 ACSL4 在 NSCLC 中的診斷以及預(yù)后意義。為了評(píng)估 ACSL4 對(duì) NSCLC 細(xì)胞系中鐵死亡的影響，本研究中使用了一種鐵死亡誘導(dǎo)劑，即erastin。在 NSCLC 組織中，ACSL4 表達(dá)水平顯著降低（p < 0.001），這與對(duì) Oncomine 和 TCGA 數(shù)據(jù)庫(kù)的調(diào)查結(jié)果一致。之后，免疫組織化學(xué)分析的結(jié)果顯示，與正常樣本相比，NSCLC樣本中的ACSL4染色減弱。結(jié)果表明，ACSL4 的差異表達(dá)與癌癥的分期、吸煙行為和淋巴結(jié)轉(zhuǎn)移的狀態(tài)有很大關(guān)系（所有 p < 0.001）。根據(jù)生存分析結(jié)果，在 ACSL4 表達(dá)升高的 NSCLC 患者中，無(wú)反復(fù)生存期 和 總生存期 均有利。通過(guò)基因轉(zhuǎn)染上調(diào) ACSL4 可以重新建立癌細(xì)胞中的鐵死亡敏感性。從機(jī)制上講，蛋白質(zhì)泛素化可以在 ACSL4 誘導(dǎo)的鐵死亡中發(fā)揮顯著的作用。 ACSL4 在鐵死亡中具有作為貢獻(xiàn)者和監(jiān)測(cè)者的功能，在 NSCLC 中顯示下調(diào)。這一發(fā)現(xiàn)表明 ACSL4 可能作為一種有用的診斷和預(yù)后生物學(xué)標(biāo)志物發(fā)揮作用，也可能被認(rèn)為是 NSCLC 的一種新的可能治療靶點(diǎn)。

腫瘤發(fā)生與反復(fù)轉(zhuǎn)移國(guó)際數(shù)據(jù)庫(kù)描述：

Acyl-CoA synthetase long-chain family member 4 (ACSL4) has been linked to the occurrence of tumors and is implicated in the ferroptosis process. Deep learning has been applied to many areas in health care, including imaging diagnosis, digital pathology, classification of cancer, and prediction of metastasis. Nonetheless, neither the level of ACSL4 expression nor its predictive significance in non-small-cell lung cancer (NSCLC) is well understood at this time. Predictions of the ACSL4 mRNA expressions in NSCLC and its link to NSCLC prognosis were made with the aid of the Oncomine and TCGA databases. By performing real-time PCR, we detected the levels of ACSL4 expression that were present in human NSCLC samples. Analyses of the diagnostic, as well as the prognostic significance of ACSL4 in NSCLC, were performed with the use of Kaplan-Meier curves. To assess the influence of ACSL4 on ferroptosis in NSCLC cell lines, an inducer of ferroptosis, namely, erastin, was utilized in this study. In NSCLC tissues, there was a substantial decrease in the level of ACSL4 expression (p?< 0.001), and this was in line with the findings of the inquiry into the Oncomine and TCGA databases. After that, the findings of the immunohistochemistry analysis revealed that the ACSL4 staining was weakened in NSCLC samples in contrast with the normal samples. It was shown that the differential expression of ACSL4 was substantially linked to the stages of cancer, smoking behaviors, and the status of nodal metastases (all?p?< 0.001). According to the findings of the survival analysis, both RFS and OS were favorable among NSCLC patients who had elevated expression of ACSL4. The ferroptosis sensitization in cancer cells may be reestablished with upregulation of ACSL4 through gene transfection. Mechanistically, protein ubiquitination could perform a remarkable function in ACSL4-induced ferroptosis. ACSL4, which has a function in ferroptosis as both a contributor and monitor, was shown to be downregulated in NSCLC. This finding suggests that ACSL4 might function as a helpful diagnostic and prognostic biological marker and might also be considered a novel possible treatment target for NSCLC.

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