Scholarlink

<p>The<i> α</i><sub>1A</sub>-adrenergic receptor, encoded by <i>ADRA1A</i>, couples to heterotrimeric G<sub>q/11</sub> proteins, promoting intracellular calcium mobilization and PKC activation. In human hepatocytes, it regulates acute metabolic responses and impacts gene expression. Although fundamental hepatic functions of <i>ADRA1A</i> have been described, its role in hepatocellular carcinoma remains elusive. We hypothesized that <i>ADRA1A</i> expressed in liver cancer tissue is part of a signaling repertoire potentially linked to patient outcomes. We analyzed The Cancer Genome Atlas liver cancer datasets and found <i>ADRA1A</i> gene deletion in 6% of patients and more prolonged survival of patients with high <i>ADRA1A</i> expression. Thus, we aimed to identify <i>ADRA1A</i>-signaling partners equally linked to more prolonged patient survival. Through a rational data mining strategy, based on the identification of the signaling repertoire linked to <i>ADRA1A</i> expression and statistical correlation with patient survival, we identified a transcriptional signature integrated by the adrenoceptor and five candidate signaling companions including two RhoGEFs: <i>FGD4</i> and <i>FARP2</i>, a phospholipid phosphatase: <i>PLPP6</i>, a RabGAP: <i>TBC1D2B</i>, and an RTK adaptor: <i>BAIAP2</i>. Additionally, highly co-expressed GPCRs such as <i>ACKR2</i>, <i>DRD1</i>, <i>ADRA1B</i>, <i>GPR17</i>, <i>S1PR1</i>, and <i>GPR182</i>, and RTKs like <i>KDR</i> and <i>TEK</i> similarly integrated transcriptional signatures with <i>ADRA1A</i> that correlated with more prolonged survival. Most <i>ADRA1A</i> candidate signaling partners were well-co-expressed with hepatocyte markers, suggesting that integrating <i>ADRA1A</i>-associated signaling networks could improve liver cancer patients’ prognosis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

α1A-Adrenergic receptor (ADRA1A) signaling signatures as prognostic biomarkers in liver hepatocellular carcinoma: a bioinformatic analysis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月31日

查看全文
  • Yarely Mabell Beltrán-Navarro,
  • José Vázquez-Prado,
  • Guadalupe Reyes-Cruz,
  • Jesús Adolfo García-Sáinz

摘要

The α1A-adrenergic receptor, encoded by ADRA1A, couples to heterotrimeric Gq/11 proteins, promoting intracellular calcium mobilization and PKC activation. In human hepatocytes, it regulates acute metabolic responses and impacts gene expression. Although fundamental hepatic functions of ADRA1A have been described, its role in hepatocellular carcinoma remains elusive. We hypothesized that ADRA1A expressed in liver cancer tissue is part of a signaling repertoire potentially linked to patient outcomes. We analyzed The Cancer Genome Atlas liver cancer datasets and found ADRA1A gene deletion in 6% of patients and more prolonged survival of patients with high ADRA1A expression. Thus, we aimed to identify ADRA1A-signaling partners equally linked to more prolonged patient survival. Through a rational data mining strategy, based on the identification of the signaling repertoire linked to ADRA1A expression and statistical correlation with patient survival, we identified a transcriptional signature integrated by the adrenoceptor and five candidate signaling companions including two RhoGEFs: FGD4 and FARP2, a phospholipid phosphatase: PLPP6, a RabGAP: TBC1D2B, and an RTK adaptor: BAIAP2. Additionally, highly co-expressed GPCRs such as ACKR2, DRD1, ADRA1B, GPR17, S1PR1, and GPR182, and RTKs like KDR and TEK similarly integrated transcriptional signatures with ADRA1A that correlated with more prolonged survival. Most ADRA1A candidate signaling partners were well-co-expressed with hepatocyte markers, suggesting that integrating ADRA1A-associated signaling networks could improve liver cancer patients’ prognosis.