High Expression Of Substance P And Its Receptor NK1R In Colorectal Cancer Is Associated With Tumor Progression And Prognosis

Background:Substance P(SP)belongs to the family of tachykinins and act 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 the SP/NK1R signaling may play an important role in the cancer progression and metastasis.However,the exact involvement and significance of SP and NK1R in CRC pathologies remains to be adequately deciphered.Methods:We performed Immunohistochemistry staining on tissue microarrays(TMA)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.Bioinformatics was employed to analysis SP and NK1R expression in colorectal cancer tissues and adjacent tissues.Results:SP and NK1R expression levels were up-regulated 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 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).Conclusion:Up-regulation of SP-NK1R may play a crucial role in CRC progression.Moreover,SP-NK1R expression may also be used as predictors for CRC prognosis.