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Abstract：
BACKGROUND: The growing understanding of cancer biology and the establishment of new treatment modalities has not yielded the expected results in terms of survival for Laryngeal Squamous Cell Cancer (LSCC). Early diagnosis, as well as prompt identification of patients with high risk of relapse would ensure greater chance of therapeutic success. However, this goal remains a challenge due to the absence of specific biomarkers for this neoplasm.
METHODS: Serum samples from 45 LSCC patients and 23 healthy donors were collected for miRNA expression profiling by TaqMan Array analysis. Additional 20 patients and 42 healthy volunteers were included for the validation set, reaching an equal number of clinical samples for each group. The potential diagnostic ability of the such identified three-miRNA signature was confirmed by ROC analysis. Moreover, each miRNA was analyzed for the possible correlation with HNSCC patients\' survival and TNM status by online databases Kaplan-Meier (KM) plotter and OncomiR. In silico analysis of common candidate targets and their network relevance to predict shared biological functions was finally performed by PANTHER and GeneMANIA software.
RESULTS: We characterized serum miRNA profile of LSCC patients identifying a novel molecular signature, including miR-223, miR-93 and miR-532, as circulating marker endowed with high selectivity and specificity. The oncogenic effect and the prognostic significance of each miRNA was investigated by bioinformatic analysis, denoting significant correlation with OS. To analyse the molecular basis underlying the pro-tumorigenic role of the signature, we focused on the simultaneously regulated gene targets-IL6ST, GTDC1, MAP1B, CPEB3, PRKACB, NFIB, PURB, ATP2B1, ZNF148, PSD3, TBC1D15, PURA, KLF12-found by prediction tools and deepened for their functional role by pathway enrichment analysis. The results showed the involvement of 7 different biological processes, among which inflammation, proliferation, migration, apoptosis and angiogenesis.
CONCLUSIONS: In conclusion, we have identified a possible miRNA signature for early LSCC diagnosis and we assumed that miR-93, miR-223 and miR-532 could orchestrate the regulation of multiple cancer-related processes. These findings encourage the possibility to deepen the molecular mechanisms underlying their oncogenic role, for the desirable development of novel therapeutic opportunities based on the use of short single-stranded oligonucleotides acting as non-coding RNA antagonists in cancer.
METHODS: Serum samples from 45 LSCC patients and 23 healthy donors were collected for miRNA expression profiling by TaqMan Array analysis. Additional 20 patients and 42 healthy volunteers were included for the validation set, reaching an equal number of clinical samples for each group. The potential diagnostic ability of the such identified three-miRNA signature was confirmed by ROC analysis. Moreover, each miRNA was analyzed for the possible correlation with HNSCC patients\' survival and TNM status by online databases Kaplan-Meier (KM) plotter and OncomiR. In silico analysis of common candidate targets and their network relevance to predict shared biological functions was finally performed by PANTHER and GeneMANIA software.
RESULTS: We characterized serum miRNA profile of LSCC patients identifying a novel molecular signature, including miR-223, miR-93 and miR-532, as circulating marker endowed with high selectivity and specificity. The oncogenic effect and the prognostic significance of each miRNA was investigated by bioinformatic analysis, denoting significant correlation with OS. To analyse the molecular basis underlying the pro-tumorigenic role of the signature, we focused on the simultaneously regulated gene targets-IL6ST, GTDC1, MAP1B, CPEB3, PRKACB, NFIB, PURB, ATP2B1, ZNF148, PSD3, TBC1D15, PURA, KLF12-found by prediction tools and deepened for their functional role by pathway enrichment analysis. The results showed the involvement of 7 different biological processes, among which inflammation, proliferation, migration, apoptosis and angiogenesis.
CONCLUSIONS: In conclusion, we have identified a possible miRNA signature for early LSCC diagnosis and we assumed that miR-93, miR-223 and miR-532 could orchestrate the regulation of multiple cancer-related processes. These findings encourage the possibility to deepen the molecular mechanisms underlying their oncogenic role, for the desirable development of novel therapeutic opportunities based on the use of short single-stranded oligonucleotides acting as non-coding RNA antagonists in cancer.
摘要：
背景：在喉鳞状细胞癌（LSCC）的生存方面，对癌症生物学的理解和新治疗方式的建立并没有产生预期的结果。早期诊断,以及迅速识别具有高复发风险的患者将确保更大的治疗成功机会。然而,由于缺乏针对该肿瘤的特异性生物标志物,这一目标仍然是一个挑战.
方法:收集来自45名LSCC患者和23名健康供体的血清样品用于通过TaqMan阵列分析的miRNA表达谱分析。另外20名患者和42名健康志愿者被纳入验证集，达到每组相同数量的临床样本。通过ROC分析证实了这种鉴定的三-miRNA特征的潜在诊断能力。此外，通过在线数据库Kaplan-Meier(KM)绘图仪和OncomiR分析了每种miRNA与HNSCC患者生存和TNM状态的可能相关性.最终通过PANTHER和GeneMANIA软件对常见候选靶标及其预测共享生物学功能的网络相关性进行了计算机模拟分析。
结果：我们表征了LSCC患者的血清miRNA谱，鉴定了一种新的分子特征，miR-223、miR-93和miR-532作为循环标记物具有高选择性和特异性。通过生物信息学分析研究了每种miRNA的致癌作用和预后意义，表示与OS显著相关。为了分析签名的促肿瘤作用的分子基础，我们专注于同时调节的基因靶标-IL6ST，GTDC1,MAP1B,CPEB3,PRKACB,NFIB,PURB,ATP2B1,ZNF148,PSD3,TBC1D15,PURA,KLF12-通过预测工具发现，并通过途径富集分析加深了它们的功能作用。结果显示参与了7种不同的生物过程，其中炎症，扩散,迁移,细胞凋亡和血管生成。
结论：结论：我们已经确定了用于早期LSCC诊断的可能的miRNA特征,并且我们假设miR-93,miR-223和miR-532可以协调多种癌症相关过程的调节.这些发现鼓励加深其致癌作用的分子机制的可能性，基于在癌症中用作非编码RNA拮抗剂的短单链寡核苷酸的使用，用于开发新的治疗机会。
方法:收集来自45名LSCC患者和23名健康供体的血清样品用于通过TaqMan阵列分析的miRNA表达谱分析。另外20名患者和42名健康志愿者被纳入验证集，达到每组相同数量的临床样本。通过ROC分析证实了这种鉴定的三-miRNA特征的潜在诊断能力。此外，通过在线数据库Kaplan-Meier(KM)绘图仪和OncomiR分析了每种miRNA与HNSCC患者生存和TNM状态的可能相关性.最终通过PANTHER和GeneMANIA软件对常见候选靶标及其预测共享生物学功能的网络相关性进行了计算机模拟分析。
结果：我们表征了LSCC患者的血清miRNA谱，鉴定了一种新的分子特征，miR-223、miR-93和miR-532作为循环标记物具有高选择性和特异性。通过生物信息学分析研究了每种miRNA的致癌作用和预后意义，表示与OS显著相关。为了分析签名的促肿瘤作用的分子基础，我们专注于同时调节的基因靶标-IL6ST，GTDC1,MAP1B,CPEB3,PRKACB,NFIB,PURB,ATP2B1,ZNF148,PSD3,TBC1D15,PURA,KLF12-通过预测工具发现，并通过途径富集分析加深了它们的功能作用。结果显示参与了7种不同的生物过程，其中炎症，扩散,迁移,细胞凋亡和血管生成。
结论：结论：我们已经确定了用于早期LSCC诊断的可能的miRNA特征,并且我们假设miR-93,miR-223和miR-532可以协调多种癌症相关过程的调节.这些发现鼓励加深其致癌作用的分子机制的可能性，基于在癌症中用作非编码RNA拮抗剂的短单链寡核苷酸的使用，用于开发新的治疗机会。
