Chen Xiao-Yi, Ru Guo-Qing, Ma Ying-Yu, Xie Jun, Chen Wan-Yuan, Wang Hui-Ju, Wang Shi-Bing, Li Li, Jin Ke-Tao, He Xiang-Lei, Mou Xiao-Zhou
Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China.
Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China.
Onco Targets Ther. 2016 Jun 16;9:3595-602. doi: 10.2147/OTT.S102356. eCollection 2016.
Epidemiologic evidence suggests that chronic inflammation and/or chronic infection is associated with cancer development, and the inflammatory process may play a crucial role in the carcinogenesis and prognosis of colorectal cancer (CRC). Substance P (SP) belongs to the family of tachykinins and acts as an immunomodulator, binding to the neurokinin-1 receptor (NK1R) to initiate tumor cell proliferation, angiogenesis, and migration, steps that are critical for tumor cell invasion and metastasis. It is suggested that SP/NK1R signaling may play an important role in cancer progression and metastasis. However, the exact involvement and significance of SP and NK1R in CRC pathologies remain to be adequately deciphered.
We performed immunohistochemistry staining on tissue microarrays containing 267 pairs of CRC and adjacent normal tissues to evaluate the clinical significance of SP or NK1R in the progression and prognosis of CRC. We also explored the potential correlation between SP and NK1R in CRC development.
Expression levels of SP and NK1R were upregulated in CRC compared with their expressions in adjacent normal tissues (P<0.001). High expression of SP in CRC was significantly associated with lymph node metastasis (P<0.001). We also found that high expression of NK1R in CRC was significantly related to TNM (tumor node metastasis) stage (P=0.010) and lymph node metastasis (P=0.019). A high correlation between SP and NK1R expression was also observed (r=0.419, P<0.001). Survival analysis showed that CRC patients with high expression of SP or NK1R have a poor prognosis when compared to patients with low SP or NK1R expression (log rank test, P<0.05). Multivariate analysis using Cox regression model showed that survival was independently correlated with lymph node metastasis, distant metastasis, and SP expression (P<0.05).
Upregulation of SP-NK1R may play a crucial role in CRC progression. Moreover, SP-NK1R expression may also be used as a predictor for CRC prognosis.
流行病学证据表明，慢性炎症和/或慢性感染与癌症发生有关，炎症过程可能在结直肠癌（CRC）的致癌作用和预后中起关键作用。P物质（SP）属于速激肽家族，作为一种免疫调节剂，与神经激肽-1受体（NK1R）结合，启动肿瘤细胞增殖、血管生成和迁移，这些步骤对肿瘤细胞侵袭和转移至关重要。有人提出，SP/NK1R信号通路可能在癌症进展和转移中起重要作用。然而，SP和NK1R在CRC病理中的具体参与情况和意义仍有待充分阐明。
我们对包含267对CRC及其相邻正常组织的组织芯片进行免疫组化染色，以评估SP或NK1R在CRC进展和预后中的临床意义。我们还探讨了CRC发展过程中SP与NK1R之间的潜在相关性。
与相邻正常组织相比，CRC中SP和NK1R的表达水平上调（P<0.001）。CRC中SP的高表达与淋巴结转移显著相关（P<0.001）。我们还发现，CRC中NK1R的高表达与TNM（肿瘤-淋巴结-转移）分期（P=0.010）和淋巴结转移（P=0.019）显著相关。还观察到SP与NK1R表达之间存在高度相关性（r=0.419，P<0.001）。生存分析表明，与SP或NK1R低表达的患者相比，SP或NK1R高表达的CRC患者预后较差（对数秩检验，P<0.05）。使用Cox回归模型进行的多变量分析表明，生存与淋巴结转移、远处转移和SP表达独立相关（P<0.05）。
SP-NK1R的上调可能在CRC进展中起关键作用。此外，SP-NK1R表达也可作为CRC预后的预测指标。
