Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji, Tokyo, Japan.
Oncotarget. 2022 May 25;13:747-754. doi: 10.18632/oncotarget.28235. eCollection 2022.
Although HOXB9 induces tumor proliferation and chemoresistance in several cancer cells, little is known in pancreatic ductal adenocarcinoma (PDAC). In the present study, increased expression of HOXB9 in PDAC was associated with the induction of angiogenic factors and poor overall survival through the TGFβ pathway. Taken together, these results suggested that HOXB9 expression in PDAC could be a surrogate marker in clinical treatment.
, angiogenic factors, TGFβ signature, Epithelial Mesenchymal Transition (EMT) marker, and chemoresistance were examined in PDAC cell lines by HOXB9 knockdown system. And the reverse effect was confirmed by using TGFβ1 recombinant. Furthermore, in clinical specimens, the correlation between HOXB9 expression and TGFβ signature was analyzed, and the relationship with clinical outcomes were investigated.
HOXB9 expression regulated the expression of TGFβ1 signature, angiogenic factors, and EMT markers , and TGFβ1 recombinant made the reverse effect of these results. And HOXB9 expression regulated the resistance to chemotherapy (Gemcitabine and nab-Paclitaxel) and stem cell population. Moreover, increased HOXB9 expression was significantly associated with poor disease-free survival the prognosis for overall survival. And, a significant positive correlation was observed between HOXB9 expression and several TGFβ signatures in clinical specimens.
In conclusion, HOXB9 expression could mediate angiogenesis, EMT, and cancer stemness through the TGFβ pathway, thereby resulting in chemoresistance and poor overall outcomes in patients with pancreatic cancer. Our results suggested that HOXB9 may clinically serve as a novel surrogate biomarker.
虽然 HOXB9 在几种癌细胞中诱导肿瘤增殖和化疗耐药，但在胰腺导管腺癌 (PDAC) 中知之甚少。在本研究中，PDAC 中 HOXB9 的表达增加与通过 TGFβ 途径诱导血管生成因子和总体生存不良有关。总之，这些结果表明 PDAC 中 HOXB9 的表达可能是临床治疗的替代标志物。
通过 HOXB9 敲低系统在 PDAC 细胞系中检查血管生成因子、TGFβ 特征、上皮间质转化 (EMT) 标志物和化疗耐药性。并通过使用 TGFβ1 重组来确认相反的效果。此外，在临床标本中，分析了 HOXB9 表达与 TGFβ 特征之间的相关性，并研究了与临床结果的关系。
HOXB9 表达调节 TGFβ1 特征、血管生成因子和 EMT 标志物的表达，TGFβ1 重组产生了这些结果的相反效果。HOXB9 表达调节对化疗（吉西他滨和 nab-紫杉醇）和干细胞群体的耐药性。此外，HOXB9 表达增加与无病生存期不良以及总体生存期预后显著相关。并且，在临床标本中观察到 HOXB9 表达与几个 TGFβ 特征之间存在显著的正相关。
总之，HOXB9 表达可通过 TGFβ 途径介导血管生成、EMT 和癌症干性，从而导致胰腺癌患者的化疗耐药和总体预后不良。我们的结果表明，HOXB9 可能在临床上作为一种新的替代生物标志物。
