Serum YKL-40 and colorectal cancer

Cintin, C.; Johansen, Julia S.; Christensen, Ib Jarle; Price, Paul A.; Sørensen, Steen; Nielsen, Hans Jørgen

doi:10.1038/sj.bjc.6690238

Cited by 178 publications

(194 citation statements)

References 28 publications

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“…1 Both tumor cells and tumor-associated macrophages produce YKL-40. 2 Plasma YKL-40 is high in patients with gastrointestinal, [3][4][5] breast, 6 lung, 7 prostate 8 and other cancer, [9][10][11] and is also associated with tumour burden and prognosis after a cancer diagnosis. 5,[12][13][14][15][16] Furthermore, high plasma YKL-40 predicts high risk of gastrointestinal cancer in the general population.…”

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confidence: 99%

Observational and genetic plasma YKL‐40 and cancer in 96,099 individuals from the general population

Kjærgaard

Nordestgaard

Johansen

et al. 2015

Intl Journal of Cancer

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Plasma YKL-40 is high in patients with cancer and in individuals who later develop cancer. Whether YKL-40 is only a marker or indeed a cause of cancer is presently unknown. We tested the hypothesis that observationally and genetically, high plasma YKL-40 is associated with high risk of cancer. For this purpose, we performed cohort and Mendelian randomization studies in 96,099 individuals from the Danish general population. Plasma levels of YKL-40 were measured in 21,643 and CHI3L1 rs4950928 was genotyped in 94,568 individuals. From 1943 through 2011, 2,291 individuals developed gastrointestinal cancer, 913 developed lung cancer, 2,863 women developed breast cancer, 1,557 men developed prostate cancer and 5,146 individuals developed other cancer. Follow-up was 100% complete. Multifactorially and CRP adjusted hazard ratio (HR) for gastrointestinal cancer was 1.82 (95%CI, 1.16-2.86) for 96-100% versus 0-33% YKL-40 percentile category. Corresponding HR were 1.71 (0.95-3.07) for lung cancer, but insignificant for breast cancer, prostate cancer and other cancers. CHI3L1 rs4950928 genotype was associated with plasmaYKL-40 levels, but not with risk of any cancer category. For gastrointestinal cancer, a doubling in YKL-40 was associated with a multifactorially and CRP adjusted observational HR of 1.14(1.05-1.23) for gastrointestinal cancer, but a corresponding genetic odds ratio of 1.06(0.94-1.18). For lung cancer, corresponding risk estimates were 1.11(1.00-1.22) observationally and 1.01(0.84-1.20) genetically. For other cancer categories, observational and genetic findings were insignificant. This study shows that high plasma YKL-40 levels were associated with high risk of gastrointestinal and likely of lung cancer, but genetic high levels were not.Inflammation plays an important role in cancer development and/or progression. 1 Both tumor cells and tumor-associated macrophages produce YKL-40. 2 Plasma YKL-40 is high in patients with gastrointestinal, 3-5 breast, 6 lung, 7 prostate 8 and other cancer, 9-11 and is also associated with tumour burden and prognosis after a cancer diagnosis. 5,[12][13][14][15][16] Furthermore, high plasma YKL-40 predicts high risk of gastrointestinal cancer in the general population. 17 Whether YKL-40 is only a marker of inflammation and cancer or plays a causal role in the development of cancer is presently unknown.A single nucleotide polymorphism in the proximal promoter of chitinase-3-like-1 (same as YKL-40; CHI3L1), rs4950928, accounts for 9.4% of the variance of plasma YKL-40. 18 MYC/MAX transcriptional factors bind better to the major than to the minor allele of rs4950928 in the gene promoter, 19 thereby presumably increasing CHI3L1 transcription and elevating plasma YKL-40 levels in carriers of the major versus minor allele. [20][21][22] We tested the hypothesis that observationally and genetically high plasma YKL-40 is associated with high risk of cancer. For this purpose, we performed cohort and Mendelian randomization studies in 96,099 individuals from the Danish general population...

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confidence: 99%

Observational and genetic plasma YKL‐40 and cancer in 96,099 individuals from the general population

Kjærgaard

Nordestgaard

Johansen

et al. 2015

Intl Journal of Cancer

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“…It was first isolated from porcine VSMC, which is highly induced during nodule formation, but the precise function of this gene is presently unknown. High serum expression of YKL-40 has been associated with poor prognosis in colorectal cancer (Cintin et al, 1999), glioblastoma multiforme (Tanwar et al, 2002), breast cancer (Johansen et al, 1995), ovarian cancer (Dehn et al, 2003), and lung cancer (Johansen et al, 2004). Consistent with the function of CLU, overexpression of YKL-40 has been implicated in increased migration and tissue remodeling.…”

Section: Discussionmentioning

confidence: 99%

Clusterin plays an important role in hepatocellular carcinoma metastasis

et al. 2005

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To identify genes associated with tumor metastasis in hepatocellular carcinoma (HCC), gene expression profiles between a pair of primary HCC (H2-P) and their matched metastatic HCC (H2-M) were compared. Overexpression of clusterin (CLU) was found in H2-M cells. To determine the roles CLU played in HCC metastasis, CLU was transfected into H2-P cells. Overexpression of CLU in H2-P cells increased cell migration by twofold in vitro and formation of metastatic tumor nodules in liver by eightfold in vivo. To evaluate the correlation of CLU expression with HCC metastasis, the expression levels of CLU in HCCs were investigated using a tissue microarray (TMA) containing 104 pairs of primary HCCs and their matched metastases. The frequency of CLU overexpression increased significantly in metastatic HCCs (59.1%) compared with that in primary tumors (32.6%, Po0.001). To gain additional insight into the function of CLU, the expression profile of H2P-CLU was compared with vector-transfected H2-P cells by cDNA microarray. A total of 35 upregulated and 14 downregulated genes were detected in H2P-CLU. One of the upregulated genes known as YKL-40, which is implicated in matrix-remodeling and metastasis, was further studied using TMA. A significant correlation (Po0.001) between the expression levels of YKL-40 and CLU was observed, implying that the CLU-YKL-40 pathway may play an important role in HCC metastasis.

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“…22 We expected that elevated serum YKL-40 levels would return to levels within the normal range after curative resection of colorectal carcinoma, since the protein might reflect the tumor burden. The current results showed that serum YKL-40 decreased in the first postoperative blood sample six months after the operation compared to the preoperative level in 62% of the patients who had elevated preoperative serum YKL-40.…”

Section: Discussionmentioning

confidence: 99%

“…22 Like CEA, YKL-40 cannot be used as a single screening test for colorectal carcinoma, since only 26% of patients with colorectal carcinoma have elevated serum YKL-40 levels at the time of operation. 22 It has been suggested that high serum YKL-40 levels might be useful as an independent preoperative predictor for poor survival in patients with colorectal carcinoma. 22 However, a prognostic marker specifically associated with the presence of a tumor may be changed by resection of the tumor.…”

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confidence: 99%

“…22 It has been suggested that high serum YKL-40 levels might be useful as an independent preoperative predictor for poor survival in patients with colorectal carcinoma. 22 However, a prognostic marker specifically associated with the presence of a tumor may be changed by resection of the tumor. Therefore, the aim of the current study was to evaluate changes in pre-to postoperative serum YKL-40 levels in patients who underwent curative resection for colorectal carcinoma to determine whether postoperative elevation in serum YKL-40 levels may be related to relapse or short survival time.…”

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confidence: 99%

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