Human Equilibrative Nucleoside Transporter 1: Novel Biomarker and Prognostic Indicator for Patients with Gemcitabine-Treated Pancreatic Cancer.

IF 2.6 4区医学 Q3 ONCOLOGY Cancer Management and Research Pub Date : 2024-06-21 eCollection Date: 2024-01-01 DOI:10.2147/CMAR.S465098

Jianchun Xiao, Fangyu Zhao, Wenhao Luo, Gang Yang, Yicheng Wang, Jiangdong Qiu, Yueze Liu, Lei You, Lianfang Zheng, Taiping Zhang

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Abstract

Aim: This article aimed to find appropriate pancreatic cancer (PC) patients to treat with Gemcitabine with better survival outcomes by detecting hENT1 levels.

Methods: We collected surgical pathological tissues from PC patients who received radical surgery in our hospital from September 2004 to December 2014. A total of 375 PC tissues and paired adjacent nontumor tissues were employed for the construction of 4 tissue microarrays (TMAs). The quality of the 4 TMAs was examined by HE staining. We performed immunohistochemistry analysis to evaluate hENT1 expression in the TMAs. Moreover, we detected hENT1 expression level and proved the role of hENT1 in cell proliferation, drug resistance, migration and invasion in vivo and vitro.

Results: The results indicated that low hENT1 expression indicated a significantly poor outcome in PC patients, including shortened DFS (21.6±2.8 months versus 36.9±4.0 months, p<0.001) and OS (33.6±3.9 versus 39.6±3.9, p=0.004). Meanwhile, patients in stage I/II of TNM stage had a longer OS (40.2±3.4 versus 15.4±1.7, p=0.002) and DFS (31.0±3.1 versus 12.4±1.9, p=0.016) than patients in stage III/IV. Patients in M0 stage had a longer OS (39.7±3.4 versus 16.2±1.9, p=0.026) and DFS(30.7±3.0 versus 11.8±2.2, p=0.031) than patients in M1 stage, and patients with tumors not invading the capsule had a better DFS than those with tumor invasion into the capsule (30.8±3.0 versus 12.6±2.3, p=0.053). Patients with preoperative CA19-9 values ≤467 U/mL have longer DFS than that of patients who had preoperative CA19-9 values >467 U/mL (37.9±4.1 versus 22.9±4.0, p=0.04). In the subgroup analysis, a high hENT1 expression level was related to a longer OS(39.4±4.0 versus 31.5±3.9, p=0.001) and DFS(35.7±4.0 versus 20.6±2.7; p<0.0001) in the Gemcitabine subgroup.

Conclusion: PC patients with high hENT1 expression have a better survival outcomes when receiving Gemcitabine. hENT1 expression can be a great prognostic indicator for PC patients to receive Gemcitabine treatment.

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人类平衡核苷转运体 1：吉西他滨治疗的胰腺癌患者的新型生物标记物和预后指标

目的：本文旨在通过检测hENT1的水平，找到适合使用吉西他滨治疗的胰腺癌（PC）患者，以获得更好的生存结果：我们收集了2004年9月至2014年12月在我院接受根治术的PC患者的手术病理组织。方法：我们收集了本院 2004 年 9 月至 2014 年 12 月接受根治术的 PC 患者的手术病理组织，共 375 份 PC 组织和配对的相邻非肿瘤组织，用于构建 4 个组织芯片（TMA）。通过 HE 染色检查了 4 个 TMA 的质量。我们进行了免疫组化分析，以评估 hENT1 在 TMAs 中的表达。此外，我们还检测了 hENT1 的表达水平，并证明了 hENT1 在体内和体外细胞增殖、耐药性、迁移和侵袭中的作用：结果表明，hENT1低表达表明PC患者的预后明显较差，包括DFS缩短（21.6±2.8个月对36.9±4.0个月，p467 U/mL（37.9±4.1对22.9±4.0，p=0.04）。在亚组分析中，hENT1高表达水平与较长的OS（39.4±4.0对31.5±3.9，p=0.001）和DFS（35.7±4.0对20.6±2.7；p结论：hENT1高表达可作为PC患者接受吉西他滨治疗的重要预后指标。

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来源期刊

Cancer Management and Research Medicine-Oncology

CiteScore

7.40

自引率

0.00%

发文量

448

审稿时长

16 weeks

期刊介绍： Cancer Management and Research is an international, peer reviewed, open access journal focusing on cancer research and the optimal use of preventative and integrated treatment interventions to achieve improved outcomes, enhanced survival, and quality of life for cancer patients. Specific topics covered in the journal include: ◦Epidemiology, detection and screening ◦Cellular research and biomarkers ◦Identification of biotargets and agents with novel mechanisms of action ◦Optimal clinical use of existing anticancer agents, including combination therapies ◦Radiation and surgery ◦Palliative care ◦Patient adherence, quality of life, satisfaction The journal welcomes submitted papers covering original research, basic science, clinical & epidemiological studies, reviews & evaluations, guidelines, expert opinion and commentary, and case series that shed novel insights on a disease or disease subtype.