BACKGROUND In colorectal cancer (CRC), inflammatory responses have been reported to associate with patient survival. However, the specific signalling pathways responsible for regulating inflammatory responses are not clear. Src family kinases (SFKs) impact tumourigenic processes, including inflammation. METHODS The relationship between SFK expression, inflammatory responses and cancer specific survival (CSS) in stage I-III CRC patients was assessed using immunohistochemistry on a 272 patient discovery cohort and an extended 822 patient validation cohort. RESULTS In the discovery cohort, cytoplasmic FGR associated with improved CSS (P = 0.019), with membrane HCK (p = 0.093) trending towards poorer CSS. In the validation cohort membrane FGR (p = 0.016), membrane HCK (p = 0.019), and cytoplasmic HCK (p = 0.030) all associated with poorer CSS. Both markers also associated with decreased proliferation and cytotoxic T-lymphocytes (all p < 0.05). Furthermore, cytoplasmic HCK was an independent prognostic marker compared to common clinical factors. To assess synergy a combine FGR + HCK score was assessed. The membrane FGR + HCK score strengthened associations with poor prognosis (p = 0.006), decreased proliferation (p < 0.001) and cytotoxic T-lymphocytes (p < 0.001). CONCLUSIONS SFKs associate with prognosis and the local inflammatory response in patients with stage I-III CRC. Active membrane FGR and HCK work in parallel to promote tumour progression and down-regulation of the local inflammatory lymphocytic response.

中文翻译：

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Src家族激酶HCK和FGR与大肠癌的局部炎症和肿瘤进展有关。

背景技术在大肠癌（CRC）中，据报道炎症反应与患者存活有关。然而，尚不清楚负责调节炎症反应的特定信号传导途径。Src家族激酶（SFK）影响致瘤过程，包括炎症。方法在272例患者发现队列和822例患者验证队列中，采用免疫组织化学方法评估了I-III期CRC患者的SFK表达，炎症反应和癌症特异性生存（CSS）之间的关系。结果在发现队列中，胞质FGR与CSS改善相关（P = 0.019），膜HCK（p = 0.093）趋向于CSS较差。在验证队列中，膜FGR（p = 0.016），膜HCK（p = 0.019）和细胞质HCK（p = 0.030）均与较差的CSS相关。两种标记物还与增殖减少和细胞毒性T淋巴细胞相关（所有p <0.05）。此外，与常见的临床因素相比，细胞质HCK是独立的预后指标。为了评估协同作用，评估了FGR + HCK的综合得分。膜FGR + HCK评分加强了与不良预后的关联（p = 0.006），增殖降低（p <0.001）和细胞毒性T淋巴细胞（p <0.001）。结论SFKs与I-III期CRC患者的预后和局部炎症反应有关。活性膜FGR和HCK并行工作，以促进肿瘤进展和局部炎性淋巴细胞反应的下调。与常见的临床因素相比，细胞质HCK是一个独立的预后指标。为了评估协同作用，评估了FGR + HCK的综合得分。膜FGR + HCK评分加强了与不良预后的关联（p = 0.006），增殖降低（p <0.001）和细胞毒性T淋巴细胞（p <0.001）。结论SFKs与I-III期CRC患者的预后和局部炎症反应有关。活性膜FGR和HCK并行工作，以促进肿瘤进展和局部炎性淋巴细胞反应的下调。与常见的临床因素相比，细胞质HCK是一个独立的预后指标。为了评估协同作用，评估了FGR + HCK的综合得分。膜FGR + HCK评分加强了与不良预后的关联（p = 0.006），增殖降低（p <0.001）和细胞毒性T淋巴细胞（p <0.001）。结论SFKs与I-III期CRC患者的预后和局部炎症反应有关。活性膜FGR和HCK并行工作，以促进肿瘤进展和局部炎性淋巴细胞反应的下调。结论SFKs与I-III期CRC患者的预后和局部炎症反应有关。活性膜FGR和HCK并行工作，以促进肿瘤进展和局部炎性淋巴细胞反应的下调。结论SFKs与I-III期CRC患者的预后和局部炎症反应有关。活性膜FGR和HCK并行工作，以促进肿瘤进展和局部炎性淋巴细胞反应的下调。