Patel Ankit, Oshi Masanori, Yan Li, Matsuyama Ryusei, Endo Itaru, Takabe Kazuaki
Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan.
Cancers (Basel). 2021 Sep 3;13(17):4443. doi: 10.3390/cancers13174443.
Hepatocellular carcinoma is a leading cause of cancer death worldwide. The unfolded protein response (UPR) has been revealed to confer tumorigenic capacity in cancer cells. We hypothesized that a quantifiable score representative of the UPR could be used as a biomarker for cancer progression in HCC. In this study, a total of 655 HCC patients from 4 independent HCC cohorts were studied to examine the relationships between enhancement of the UPR and cancer biology and patient survival in HCC utilizing an UPR score. The UPR correlated with carcinogenic sequence and progression of HCC consistently in two cohorts. Enhanced UPR was associated with the clinical parameters of HCC progression, such as cancer stage and multiple parameters of cell proliferation, including histological grade, mKI67 gene expression, and enrichment of cell proliferation-related gene sets. The UPR was significantly associated with increased mutational load, but not with immune cell infiltration or angiogeneis across independent cohorts. The UPR was consistently associated with worse survival across independent cohorts of HCC. In conclusion, the UPR score may be useful as a biomarker to predict prognosis and to better understand HCC.
肝细胞癌是全球癌症死亡的主要原因。未折叠蛋白反应（UPR）已被揭示赋予癌细胞致瘤能力。我们假设，一个代表UPR的可量化评分可以用作肝细胞癌（HCC）癌症进展的生物标志物。在本研究中，我们利用一个UPR评分，对来自4个独立HCC队列的总共655例HCC患者进行了研究，以检验UPR增强与HCC癌症生物学及患者生存之间的关系。在两个队列中，UPR均与HCC的致癌序列和进展一致相关。UPR增强与HCC进展的临床参数相关，如癌症分期以及细胞增殖的多个参数，包括组织学分级、mKI67基因表达和细胞增殖相关基因集的富集。在独立队列中，UPR与突变负荷增加显著相关，但与免疫细胞浸润或血管生成无关。在独立的HCC队列中，UPR始终与较差的生存率相关。总之，UPR评分可能作为一种生物标志物，有助于预测预后并更好地理解HCC。
