Prognostic Value of LRG1 in Breast Cancer: A Retrospective Study

Abstract

<b><i>Background:</i></b> High expression of leucine-rich alpha-2-glycoprotein 1 (LRG1) is closely related to angiogenesis, which may play an important role in promoting invasion and metastasis. However, the current literature has yet to clarify the clinical significance of LRG1 in breast cancer. <b><i>Objectives:</i></b> The purpose of this work was to validate the correlation between LRG1 expression and prognosis in early breast cancer. <b><i>Methods:</i></b> We utilized an LRG1 detection agent in 330 cases of early breast cancer. The correlation of LRG1 expression with clinicopathological features, patient recurrence, and survival was investigated. <b><i>Results:</i></b> Compared with adjacent tissue samples, an elevated expression of LRG1 was observed in breast cancer samples. Moreover, LRG1 expression is associated with the number of lymphatic metastases and TNM pathological stage (<i>p</i> = 0.000, <i>p</i> = 0.000, respectively). For disease-free survival (DFS), the Kaplan-Meier curve indicated a poorer prognosis for the group with high LRG1 levels compared with the low LRG1 group (<i>p</i> = 0.000). A similar result was found for overall survival (OS; <i>p</i> = 0.000). The multivariate Cox regression indicated that LRG1 was still associated with DFS (HR 2.090, 95% CI 1.205–3.625, <i>p</i> = 0.009) and OS (HR 2.112, 95% CI 1.167–3.822, <i>p</i> = 0.013). The histological grade, TNM pathological stage, and molecular subtype were identified as independent risk factors affecting OS. <b><i>Conclusion:</i></b> In the malignant progression of breast cancer, high LRG1 levels are associated with lymphatic metastasis, histological grade, poor DFS, and poor OS. This study validates the use of LRG1 as a potential prognosis biomarker for early breast cancer.

LRG1 destabilizes tumor vessels and restricts immunotherapeutic potency

“…Vessels from LLC lung metastases (Figure S1C) exhibited a strong induction of Lrg1 compared with normal lung vessels in which the expression was barely detectable (Figures 1J and S1D). Overall, these observations align with our human data and previous reports, [27][28][29][30][31][32][33][34][35][36][37][38][39] and raise the possibility that local secretion of LRG1 may affect the TME of primary and metastatic tumors and, in particular, through both autocrine and paracrine signaling, vascular function.…”

“…LRG1 expression is increased in human cancer patients Under normal conditions, LRG1 is expressed predominantly by the liver, but in cancer there is strong evidence that its expression is significantly induced. [27][28][29][30][31][32][33][34][35][36][37][38][39] To confirm these findings, LRG1 protein was examined by immunohistochemistry in human lung, prostate, and breast carcinomas, with all three exhibiting high expression compared to adjacent normal-appearing tissue or normal control tissue (Figures 1A-1C). We also observed expression of LRG1 in peritumoral endothelial cells (Figure 1D).…”

LRG1 Promotes Metastatic Dissemination of Melanoma through Regulating EGFR/STAT3 Signalling

“…Neovascularization plays an essential role in tumour expansion [12] and tumour vasculature provides a route of transportation for tumour cell dissemination [13]. Indeed, altered LRG1 expression is associated with various cancers and LRG1 has been proposed as a prognosis/diagnosis marker for hepatocellular carcinoma, gastric cancer, pancreatic cancer, leukaemia, ovarian cancer, breast cancer, prostate cancer, biliary tract cancer, bladder cancer, and non-small cell lung cancer [14][15][16][17][18][19][20][21]. LRG1 regulates tumour angiogenesis by inducing VEGFA through HIF1α activation [22].…”

Discovery and Evaluation of Protein Biomarkers as a Signature of Wellness in Late-Stage Cancer Patients in Early Phase Clinical Trials

“…A low level of apolipoprotein C-III would indicate a lower capability of the body to inhibit fat degradation and low levels of apolipoprotein C-III are observed in gastric cancer where blood lipid levels are correlated with disease progression [ 44 ]. Plasma serine protease inhibitor has been shown to have links with lung and ovarian cancer with the potential use as a prognostic marker [ 43 , 44 ]. A plasma serine protease inhibitor decrease is association with cancer metastasis, migration and invasion [ 45 , 46 ].…”

“…Leucine-rich alpha-2-glycoprotein has been used recently as a potential diagnostic marker in colorectal cancer [40] and it has shown potential use as a prognostic marker and treatment target in oesophageal squamous cell carcinoma [41]. A high amount of leucine-rich alpha-2-glycoprotein has been shown to promote angiogenesis which could indicate an increased amount of cancer invasion and metastasis [43]. Apolipoprotein C-III and other apolipoproteins have been identified as being significantly abundant in liver and lung cancer and the protein family has been identified as a potential target for diagnostic and prognostic markers [42].…”