title: High expression of substance P and its receptor neurokinin-1 receptor in colorectal cancer is associated with tumor progression and prognosis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China.
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Chen
authors.affiliation: Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China.
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Ru
authors.affiliation: Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China.
authors.forename: Ying-Yu
authors.initials: YY
authors.lastname: Ma
authors.affiliation: Department of Anus-Intestines, Affiliated Hospital of Shaoxing University, Shaoxing, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China.
authors.forename: Wan-Yuan
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China.
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China.
authors.forename: Shi-Bing
authors.initials: SB
authors.lastname: Wang
authors.affiliation: Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, People's Republic of China.
authors.forename: Ke-Tao
authors.initials: KT
authors.lastname: Jin
authors.affiliation: Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China.
authors.forename: Xiang-Lei
authors.initials: XL
authors.lastname: He
authors.affiliation: Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China.
authors.forename: Xiao-Zhou
authors.initials: XZ
authors.lastname: Mou
keywords: CRC; NK1R; SP; prognosis; progression