Stromal CXCR4 and CXCL12 Expression is Associated with Distant Recurrence and Poor Prognosis in Rectal Cancer After Chemoradiotherapy
Stromal CXCR4 and CXCL12 Expression is Associated with Distant Recurrence and Poor Prognosis in Rectal Cancer After Chemoradiotherapy
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DOI：
10.1245/s10434-010-0970-y
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发表时间：
2010-08-01
影响因子：
3.7
通讯作者：
Kusunoki, Masato
中科院分区：
文献类型：
--
作者：
Saigusa, Susumu;Toiyama, Yuji;Kusunoki, Masato
远处复发仍然是接受术前放化疗（CRT）的直肠癌患者死亡的主要原因。最近，癌症基质被认为参与影响癌细胞的增殖、侵袭和转移。有报道CXCR4及其配体CXCL12的表达与结直肠癌的迁移、侵袭、增殖有关。 共有53例直肠癌患者术前接受了CRT。使用显微切割从福尔马林固定石蜡包埋 (FFPE) 标本中获取 CRT 后残余直肠癌基质细胞的总 RNA。使用实时逆转录聚合酶链反应（RT-PCR）测量CXCR4和CXCL12基因的表达水平。还对 CRT 后这些标记物的免疫组织化学染色进行了研究。在 53 名患者中，分别有 16 名 (30.1%) 和 14 名 (26.4%) 表现出可检测到的 CXCR4 和 CXCL12 水平。我们发现CXCR4和CXCL12的表达水平之间存在显着的正相关。与 CRT 后未复发患者相比，出现远处复发的患者 CXCR4 和 CXCL12 表达水平高出一倍（P < 0.01）。表达水平升高还与这两个基因的无复发生存概率较差相关（P < 0.01）。此外，CXCL12 阳性表达（而非 CXCR4）与较差的总生存率显着相关（P < 0.01）。使用免疫组织化学测定的 CXCR4 和 CXCL12 表达不仅在癌症中而且还在基质细胞中观察到。我们的结果表明，评估这两种基因的表达可能有助于预测术前 CRT 和手术治疗的直肠癌患者的远处复发和不良预后。
Distant recurrence remains the major cause of mortality in rectal cancer patients with preoperative chemoradiotherapy (CRT). Recently, cancer stroma has been implicated in influencing proliferation, invasion, and metastasis of cancer cells. It has been reported that expression of CXCR4 and its ligand CXCL12 are associated with migration, invasion, and proliferation of colorectal cancer.A total of 53 patients with rectal cancer underwent preoperative CRT. Total RNAs of residual rectal cancer stromal cells after CRT were obtained from formalin-fixed paraffin-embedded (FFPE) specimens using microdissection. The expression levels of CXCR4 and CXCL12 genes were measured using real-time reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemical staining of these markers after CRT was also investigated.Of the 53 patients, 16 (30.1%) and 14 (26.4%) showed detectable CXCR4 and CXCL12 levels, respectively. We found a significant positive correlation between expression levels of CXCR4 and CXCL12. Patients who developed distant recurrence had twofold higher expression levels of both CXCR4 and CXCL12 compared with those without recurrence after CRT (P < 0.01). Elevated expression levels were also associated with poor probability of recurrence-free survival in both genes (P < 0.01). Additionally, positive CXCL12 expression, but not CXCR4, was significantly correlated with poorer overall survival (P < 0.01). CXCR4 and CXCL12 expression determined using immunohistochemistry was observed in not only cancer but also stromal cells.Our results suggest that evaluation of the expression of both genes may be useful for predicting distant recurrence and poor prognosis in rectal cancer patients treated with preoperative CRT followed by surgery.