Dataset Information

Serum chemokine (CC motif) ligand 2 level as a diagnostic, predictive, and prognostic biomarker for prostate cancer.

ABSTRACT: Prostate-specific antigen (PSA) is regarded as the most sensitive biomarker for prostate cancer. Although androgen/androgen receptor (AR) signaling promotes prostate cancer progression, suppression of AR signaling induces chemokine (CC motif) ligand 2 (CCL2), which enables prostate cancer cells to gain metastatic potential. AR-controlled PSA alone may be an unreliable biomarker for patients receiving androgen deprivation therapy. Therefore, we investigated the validity of CCL2 as a complementary biomarker to PSA for prostate cancer. Our in vitro approach of enriching for prostate cancer cells with higher migration potential showed that CCL2 activated cellular migration. Importantly, we found that CCL2 levels were significantly different between men (n = 379) with and without prostate cancer. Patients with CCL2 ? 320 pg/mL had worse overall survival and prostate cancer -specific survival than those with CCL2 < 320 pg/mL. A novel risk classification was developed according to the risk factors CCL2 ? 320 pg/mL and PSA ? 100 ng/mL, and scores of 2, 1, and 0 were defined as poor, intermediate, and good risk, respectively, and clearly distinguished patient outcomes. CCL2 may serve as a novel biomarker for prostate cancer. The novel risk classification based on combining CCL2 and PSA is more reliable than using either alone.

SUBMITTER: Izumi K

PROVIDER: S-EPMC4885000 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Serum chemokine (CC motif) ligand 2 level as a diagnostic, predictive, and prognostic biomarker for prostate cancer.

Izumi Kouji K Mizokami Atsushi A Lin Hsiu-Ping HP Ho Hui-Min HM Iwamoto Hiroaki H Maolake Aerken A Natsagdorj Ariunbold A Kitagawa Yasuhide Y Kadono Yoshifumi Y Miyamoto Hiroshi H Huang Chiung-Kuei CK Namiki Mikio M Lin Wen-Jye WJ

Oncotarget 20160201 7

Prostate-specific antigen (PSA) is regarded as the most sensitive biomarker for prostate cancer. Although androgen/androgen receptor (AR) signaling promotes prostate cancer progression, suppression of AR signaling induces chemokine (CC motif) ligand 2 (CCL2), which enables prostate cancer cells to gain metastatic potential. AR-controlled PSA alone may be an unreliable biomarker for patients receiving androgen deprivation therapy. Therefore, we investigated the validity of CCL2 as a complementary ...[more]

PMID: 26701731

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Project description:The diagnostic and prognostic mechanisms of C?X?C motif chemokine ligand 3 (CXCL3) in colon cancer (CC) have not yet been reported. Therefore, the objective of the present study was to use cohorts of patients from Guangxi Medical University and the Gene Expression Omnibus (GEO) database to investigate and validate CXCL3 for the diagnosis and prognosis of CC, and to explore its prospective molecular mechanism. Reverse transcription?quantitative PCR (RT?qPCR) analysis of 38 paired tumor and non?tumor tissues, and immunohistochemistry (IHC) of 212 tumor and 46 non?tumor tissues was conducted to explore the expression of CXCL3 and its diagnostic and prognostic significance in the Guangxi Medical University CC cohort. A GEO dataset, GSE40967, was used to validate the prognostic significance of CXCL3. Gene set enrichment analysis (GSEA) was also conducted to explore the potential molecular mechanisms underlying the effects of CXCL3 in CC. The RT?qPCR results indicated that CXCL3 expression was significantly higher in cancer tissues compared with adjacent normal tissues, suggesting that it may have high diagnostic value for CC. Multivariate Cox analysis based on the IHC results suggested that there was no appreciable association between CXCL3 positivity and the overall survival (OS) time of CC. However, a stratified analysis revealed that high expression of CXCL3 was associated with considerably increased mortality in the subgroup of CC patients with tumor size <5 cm (adjusted P=0.042, adjusted HR=2.298, 95% CI=1.030?5.126) and with tumor thrombus (adjusted P=0.019, adjusted HR=5.096, 95% CI=1.306?19.886). In the GSE40967 dataset, high expression of CXCL3 was closely associated with poor OS in CC (adjusted P=0.049, adjusted HR=1.416, 95% CI=1.002?2.003). Furthermore, GSEA indicated that the high expression of CXCL3 was closely associated with DNA repair, cell cycle process, cell apoptosis process and the P53 regulation pathway. In summary, these result suggest that CXCL3 might serve as a novel biomarker in the diagnosis and prognosis of CC.

Dataset Information

Serum chemokine (CC motif) ligand 2 level as a diagnostic, predictive, and prognostic biomarker for prostate cancer.

Publications

Serum chemokine (CC motif) ligand 2 level as a diagnostic, predictive, and prognostic biomarker for prostate cancer.

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