Traslational Investigation Unit, University General Hospital of Ciudad Real, SESCAM, Ciudad Real, Spain.
Research Institute of Castilla-La Mancha (IDISCAM), Ciudad Real, Spain.
World J Surg Oncol. 2023 Sep 12;21(1):287. doi: 10.1186/s12957-023-03168-6.
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the main causes of cancer mortality in the world. A characteristic feature of this cancer is that a large part of the tumor volume is composed of a stroma with different cells and factors. Among these, we can highlight the cytokines, which perform their function through binding to their receptors. Given the impact of the CXCR4 receptor in the interactions between tumor cells and their microenvironment and its involvement in important signaling pathways in cancer, it is proposed as a very promising prognostic biomarker and as a goal for new targeted therapies. Numerous studies analyze the expression of CXCR4 but we suggest focusing on the expression of CXCR4 in the stroma. METHODS: Expression of CXCR4 in specimens from 33 patients with PDAC was evaluated by immunohistochemistry techniques and matched with clinicopathological parameters, overall and disease-free survival rates. RESULTS: The percentage of stroma was lower in non-tumor tissue (32.4 ± 5.2) than in tumor pancreatic tissue (67.4 ± 4.8), P-value = 0.001. The level of CXCR4 expression in stromal cells was diminished in non-tumor tissue (8.7 ± 4.6) and higher in tumor pancreatic tissue (23.5 ± 6.1), P-value = 0.022. No significant differences were identified in total cell count and inflammatory cells between non-tumor tissue and pancreatic tumor tissue. No association was observed between CXCR4 expression and any of the clinical or pathological data, overall and disease-free survival rates. Analyzing exclusively the stroma of tumor samples, the CXCR4 expression was associated with tumor differentiation, P-value = 0.05. CONCLUSIONS: In this study, we reflect the importance of CXCR4 expression in the stroma of patients diagnosed with PDAC. Our results revealed a high CXCR4 expression in the tumor stroma, which is related to a poor tumor differentiation. On the contrary, we could not find an association between CXCR4 expression and survival and the rest of the clinicopathological variables. Focusing the study on the CXCR4 expression in the tumor stroma could generate more robust results. Therefore, we consider it key to develop more studies to enlighten the role of this receptor in PDAC and its implication as a possible biomarker.
背景：胰腺导管腺癌（PDAC）是世界上癌症死亡的主要原因之一。这种癌症的一个特征是，肿瘤体积的很大一部分由具有不同细胞和因子的基质组成。在这些因子中，我们可以突出细胞因子，它们通过与受体结合来发挥作用。鉴于 CXCR4 受体在肿瘤细胞与其微环境之间的相互作用中的重要作用及其在癌症中的重要信号通路中的参与，它被提出作为一种很有前途的预后生物标志物，并作为新的靶向治疗的目标。许多研究分析了 CXCR4 的表达，但我们建议重点研究 CXCR4 在基质中的表达。
方法：通过免疫组织化学技术评估 33 例 PDAC 患者标本中 CXCR4 的表达，并与临床病理参数、总生存率和无病生存率进行匹配。
结果：非肿瘤组织的基质百分比（32.4±5.2）低于肿瘤胰腺组织（67.4±4.8），P 值=0.001。非肿瘤组织中基质细胞 CXCR4 表达水平降低（8.7±4.6），肿瘤胰腺组织中升高（23.5±6.1），P 值=0.022。非肿瘤组织和胰腺肿瘤组织的总细胞计数和炎症细胞无显著差异。CXCR4 表达与任何临床或病理数据、总生存率和无病生存率均无相关性。仅分析肿瘤样本的基质，CXCR4 表达与肿瘤分化有关，P 值=0.05。
结论：在这项研究中，我们反映了 CXCR4 在诊断为 PDAC 的患者的肿瘤基质中的表达的重要性。我们的结果显示，肿瘤基质中 CXCR4 的高表达与肿瘤分化不良有关。相反，我们没有发现 CXCR4 表达与生存和其余临床病理变量之间的相关性。将研究重点放在肿瘤基质中的 CXCR4 表达上可以产生更可靠的结果。因此，我们认为关键是开展更多的研究，阐明该受体在 PDAC 中的作用及其作为潜在生物标志物的意义。
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