Clinicopathological Significance of Leucine-Rich α2-Glycoprotein-1 in Sera of Patients With Pancreatic Cancer

Furukawa, Katsunori; Kikuchi, Kôichi; Eguchi, Hidetoshi; Tanemura, Masahiro; Tanida, Tsukasa; Tomimaru, Yoshito; Akita, Hirofumi; Hama, Naoki; Wada, Hiroshi; Kobayashi, Shogo; Nonaka, Yasuki; Takamatsu, Shinji; Shinzaki, Shinichiro; Kumada, Takashi; Satomura, Shinji; Ito, Toshifumi; Serada, Satoshi; Naka, Tetsuji; Mori, Masaki; Doki, Yuichiro; Miyoshi, Eiji; Nagano, Hiroaki

doi:10.1097/mpa.0000000000000205

Cited by 45 publications

(55 citation statements)

References 21 publications

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“…10 An increase in serum LRG was also observed in other diseases such as rheumatoid arthritis, infection, heart failure, 12 and malignant diseases. 13 Moreover, our recent study clearly demonstrated an association between LRG upregulation and clinical activity of IBD, which was superior to conventional serological biomarkers. 10 However, comprehensive analysis of the correlation between serum LRG and endoscopic disease activity of UC has not been performed.…”

Section: Introductionmentioning

confidence: 77%

Leucine-rich Alpha-2 Glycoprotein is a Serum Biomarker of Mucosal Healing in Ulcerative Colitis

Shinzaki

Matsuoka

Iijima

et al. 2016

Journal of Crohn's and Colitis

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109

103

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Background and Aims:Although several noninvasive and easily accessible biomarkers for inflammatory bowel disease [IBD] are available, their sensitivity and specificity are not adequate to be used as single markers and do not overrule the need for endoscopic evaluation. We previously reported that serum leucine-rich alpha-2 glycoprotein [LRG] was a novel biomarker for rheumatoid arthritis and IBD. We herein investigated whether LRG could indicate endoscopic activity in patients with ulcerative colitis [UC].Methods:Serum LRG concentrations were determined by enzyme-linked immunosorbent assay [ELISA] in consecutive 129 patients with UC in two tertiary care hospitals, and associations of LRG with clinical and endoscopic activities were evaluated. Clinical activity index [CAI] < 6 was defined as clinical remission, and mucosal healing [MH] and complete mucosal healing were defined as Matts’ endoscopic grades of 1 or 2 and grade of 1, respectively.Results:Serum LRG levels were significantly increased and correlated with clinical and endoscopic activities in patients with UC. LRG levels were associated with both clinical and endoscopic activities even in patients with normal serum C-reactive protein [CRP] levels. Furthermore, LRG levels were significantly lower in patients with complete MH and deep remission. Serial measurements of LRG levels in a subset of patients demonstrated that LRG was significantly elevated during the endoscopically active stage compared with that during the MH stage.Conclusions:Serum LRG is a novel biomarker for detecting MH during disease course in patients with UC and a surrogate marker of endoscopic inflammation in patients with normal CRP levels.

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Section: Introductionmentioning

confidence: 77%

Leucine-rich Alpha-2 Glycoprotein is a Serum Biomarker of Mucosal Healing in Ulcerative Colitis

Shinzaki

Matsuoka

Iijima

et al. 2016

Journal of Crohn's and Colitis

Self Cite

109

103

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“…A role for LRG1 has been suggested in promoting angiogenesis through activation of the TGF-b pathway (40). Apart from PDAC, increased LRG1 plasma levels have also been found in other cancer types (41)(42)(43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

Sequential Validation of Blood-Based Protein Biomarker Candidates for Early-Stage Pancreatic Cancer

Capello

Bantis

Scélo

et al. 2016

JNCI J Natl Cancer Inst

116

125

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Background: CA19-9, which is currently in clinical use as a pancreatic ductal adenocarcinoma (PDAC) biomarker, has limited performance in detecting early-stage disease. We and others have identified protein biomarker candidates that have the potential to complement CA19-9. We have carried out sequential validations starting with 17 protein biomarker candidates to determine which markers and marker combination would improve detection of early-stage disease compared with CA19-9 alone. Methods: Candidate biomarkers were subjected to enzyme-linked immunosorbent assay based sequential validation using independent multiple sample cohorts consisting of PDAC cases (n ¼ 187), benign pancreatic disease (n ¼ 93), and healthy controls (n ¼ 169). A biomarker panel for early-stage PDAC was developed based on a logistic regression model. All statistical tests for the results presented below were one-sided. Results: Six out of the 17 biomarker candidates and CA19-9 were validated in a sample set consisting of 75 PDAC patients, 27 healthy subjects, and 19 chronic pancreatitis patients. A second independent set of 73 early-stage PDAC patients, 60 healthy subjects, and 74 benign pancreatic disease patients (combined validation set) yielded a model that consisted of TIMP1, LRG1, and CA19-9. Additional blinded testing of the model was done using an independent set of plasma samples from 39 resectable PDAC patients and 82 matched healthy subjects (test set). The model yielded areas under the curve (AUCs) of 0.949 (95% confidence interval [CI] ¼ 0.917 to 0.981) and 0.887 (95% CI ¼ 0.817 to 0.957) with sensitivities of 0.849 and 0.667 at 95% specificity in discriminating early-stage PDAC vs healthy subjects in the combined validation and test sets, respectively. The performance of the biomarker panel was statistically significantly improved compared with CA19-9 alone (P < .001, combined validation set; P ¼ .008, test set).

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“…Rabbit anti‐LRG1 antibody (1:500; HPA001888; Atlas Antibodies, Stockholm, Sweden) was used for IHC. As LRG1 expression in tumor cells was primarily localized in the cytoplasm and the pattern of staining was homogeneous and diffuse, LRG1 expression was evaluated by the intensity of stained cancer samples as previously reported . Liver tissues were used as the positive control.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, recent studies have reported that LRG1 can be used as a biomarker in several types of cancer such as ovarian, lung, biliary tract, and hepatocellular carcinoma . Serum LRG1 is also detected in patients with malignancies and associated with progression of malignancies . However, no reports exist on the clinical significance of LRG1 expression in gastric cancer.…”

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confidence: 99%

Overexpression of leucine‐rich α2‐glycoprotein‐1 is a prognostic marker and enhances tumor migration in gastric cancer

et al. 2017

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Gastric cancer is one of the most common malignant tumors. Although improvement in chemotherapy has been achieved, the clinical prognosis of advanced gastric cancer remains poor. Therefore, it is increasingly important to predict the prognosis and determine whether patients should or should not receive neoadjuvant or adjuvant chemotherapy. Leucine‐rich α2‐glycoprotein‐1 (LRG1) is overexpressed during inflammation and is associated with various malignancies. In this study, we assessed LRG1 expression in cancer specimens and in the sera of patients with cancer to clarify the usefulness of LRG1 as a biomarker in gastric cancer. This study enrolled 239 (for immunohistochemical staining; IHC) and 184 (for ELISA) patients with gastric cancer. Results of IHC showed that LRG1 expression was significantly associated with histological type, lymphatic and venous invasion, tumor and node factors, and disease stage. Overall survival was significantly worse in the high LRG1 expression group than in the low LRG1 group (P = 0.0003). Cox multivariate analysis of overall survival revealed that LRG1 expression was an independent prognostic factor (P = 0.0258). Serum LRG1 was significantly higher in gastric cancer patients than in healthy volunteers, and increased as the pathological stage progressed. Furthermore, a significant correlation was revealed between serum LRG1 level and LRG1 expression with IHC (P < 0.0001). Inhibition of LRG1 significantly decreased cell proliferation in vitro (migratory and invasive capacity of gastric cancer cells). These results suggest that LRG1 expression in tumors and serum may be a useful prognostic marker in gastric cancer patients.

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Clinicopathological Significance of Leucine-Rich α2-Glycoprotein-1 in Sera of Patients With Pancreatic Cancer

Abstract: These results suggest that serum LRG-1 is a promising biomarker for pancreatic cancer.

Cited by 45 publications

References 21 publications

Leucine-rich Alpha-2 Glycoprotein is a Serum Biomarker of Mucosal Healing in Ulcerative Colitis

Leucine-rich Alpha-2 Glycoprotein is a Serum Biomarker of Mucosal Healing in Ulcerative Colitis

Sequential Validation of Blood-Based Protein Biomarker Candidates for Early-Stage Pancreatic Cancer

Overexpression of leucine‐rich α2‐glycoprotein‐1 is a prognostic marker and enhances tumor migration in gastric cancer

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