Expression of prokineticin-receptor2(PK-R2) is a new prognostic factor in human colorectal cancer

Abstract

The increased invasiveness of colorectal cancer cells is important for progression and metastasis to the surrounding organs. According to recent molecular biological studies, signaling through transmembrane Prokineticin-Receptor2(PK-R2) is likely involved in the ability of tumor cell to invade. However, no studies have evaluated the relationship between PK-R2 expression, ability of cancer to invade/metastasize, and patient prognosis in cases of resected colorectal cancer. Accordingly, we have examined these factors in the present study.Immunohistochemical staining was performed to detect PK-R2 in the primary lesion and adjacent normal large intestine mucosa of 324 colorectal cancer patients who underwent resection surgery at our department. Additionally, we conducted clinicopathologic examinations and analyzed patient prognoses with the Kaplan-Meier method. Further, multivariate analysis was conducted using a cox-proportional hazard model.PK-R2 expression was observed on the cellular membrane of the primary lesion in 147 of 324 cases (45.3%) of human colorectal cancer. PK-R2 expression was associated with a higher incidence of vascular invasion, lymph node metastasis, hepatic metastasis, and hematogenous metastasis. Further, prevalence of PK-R2 expression increased as tumor stage increased. In stage III curative resection cases, where recurrence is the most serious problem, cases that expressed PK-R2 had a significantly lower 5-year survival rate (82.1% versus 66.8%) and higher recurrence compared to those cases with no PK-R2 expression. In the multivariate analysis for prognosis, PK-R2 expression was found to be an independent factor(ratio2.621).PK-R2 expression could be one of the new prognostic factors in human colorectal cancer.

Prokineticin 2 expression as a novel prognostic biomarker for human colorectal cancer

“…Generally, the identification of patients who were at high risk of recurrence depended on pathological characteristics, such as the depth of invasion, nodal metastasis, stage group, and perforation or invasion of adjacent organs [ 7 ]. Nevertheless, the clinical outcomes are diverse among patients, including those with similar clinicopathological parameters and treatments, because CRC is a biologically heterogenous disease and causes dysfunction of multiple proteins that control cell proliferation and survival [ 8 – 10 ]. Patients who are at the same clinical stage of CRC might have distinct molecular drivers and different prognoses.…”

Risk factors of synchronous peritoneal metastases in colorectal cancer: a meta-analysis

“…The PROK1 protein was identi ed as a vascular endothelial growth factor. Increased PROK1 expression is associated with angiogenesis involving hematogenous metastasis [34,37]. Besides direct invasion and hematogenous spread, peritoneal carcinomatosis could be occurred by lymphatic dissemination, which supports the risk factor of N1-2 [54,56,57].…”

“…Reasons for exclusion were recorded. Finally, 25 studies [3,8,[15][16][17][18][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] were included in the nal analysis (Fig. 1).…”

“…Two studies [34,37], including data on 944 patients (29 synchronous pmCRC, 915 non-pmCRC) regarding PROK1/PROKR2 status, were included for eligibility in the meta-analysis. Synchronous CPM was associated positively with PROK1/PROKR2-positive (OR 2.244; 95% CI, 1.031 to 4.884; P = 0.042) (Fig.…”

Endocrine Gland-Derived Vascular Endothelial Growth Factor/Prokineticin-1 in Cancer Development and Tumor Angiogenesis

“…Tabata et al [33] reported EG-VEGF as a factor to strengthen cell invasion ability in colon cancer cell lines, by acting on MMP-2, MMP-7, and MMP-9 via prokineticin receptor 2. Later, Goi and his team defined EG-VEGF and its corresponding receptor PROKR2 as prognostic markers in colorectal carcinoma [34, 35] suggesting a common pathway with VEGF sustained by their finding regarding the enhancement of antitumor effects when it was simultaneously targeting VEGF and EG-VEGF [36]. Fewer data were reported in normal tissues about EG-VEGF mechanism of action.…”