Overexpression of CLEC3A promotes tumor progression and poor prognosis in breast invasive ductal cancer

Ni, Jun; Peng, Yun; Yang, Fumeng; Xi, Xun; Huang, Xingwei; He, Changyu

doi:10.2147/ott.s161311

Cited by 23 publications

(18 citation statements)

References 35 publications

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“…CLEC3A expression has also been reported in breast cancer tissue and high CLEC3A expression significantly correlated with poor prognosis. A previous study indicated that CLEC3A promotes invasion and metastasis of breast cancer cells by activating the PI3K/Akt signaling pathway …”

Section: Discussionmentioning

confidence: 99%

“…Referring to the previous studies, CLEC3A, MMP7, and LCN2 could play roles in tumor cell migration through the pathway as shown in Figure . Briefly, PI3K/AKT signaling pathway, activated by CLEC3A and other molecules, upregulates MMP7 and LCN2 thorough loss of PKP3, which promotes cell migration (Figure A). CLEC3A is also located in cell membrane, and support adhesion between tumor cells by interacting with Extracellular matrix (ECM) on the cell surface .…”

Section: Discussionmentioning

confidence: 99%

“…A previous study indicated that CLEC3A promotes invasion and metastasis of breast cancer cells by activating the PI3K/Akt signaling pathway. 36 Matrix metalloproteinases are a family of zinc-dependent endopeptidases. 37 MMP7 is secreted specifically by epithelial cells 38 and its overexpression has been observed in many tumor types including colorectal cancer, 38 bladder cancer, 39 gastric cancers, 40 pancreatic cancer, 41 and esophageal cancer.…”

Section: Discussionmentioning

confidence: 99%

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CLEC3A, MMP7, and LCN2 as novel markers for predicting recurrence in resected G1 and G2 pancreatic neuroendocrine tumors

et al. 2019

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Although the postoperative recurrence rate for pancreatic neuroendocrine tumors (PNETs) is reported to be 13.5%‐30%, the paucity of valuable biomarkers to predict recurrence poses a problem for the early detection of relapse. Hence, this study aimed to identify new biomarkers to predict the recurrence of PNETs. We performed RNA sequencing (RNA‐Seq) on RNA isolated from frozen primary tumors sampled from all localized G1/G2 PNETs resected curatively from 1998 to 2015 in our institution. We calculated differentially expressed genes (DEGs) in tumor with and without recurrence (≥3 years) for the propensity‐matched cohort. Gene ontology analysis for the identified DEGs was also performed. Furthermore, we evaluated the expression levels of candidate genes as recurrence predictors via immunostaining. Comparison of transcriptional levels in tumors with and without recurrence identified 166 DEGs. Up‐ and downregulated genes with high significance in these tumors were mainly related to extracellular organization and cell adhesion, respectively. We observed the top three upregulated genes, C‐type lectin domain family 3 member A (CLEC3A), matrix metalloproteinase‐7 (MMP7), and lipocalin2 (LCN2) immunohistochemically and compared their levels in recurrent and nonrecurrent tumors. Significantly higher recurrence rate was shown in patients with positive expression of CLEC3A ( P = 0.028), MMP7 ( P = 0.003), and LCN2 ( P = 0.040) than that with negative expression. We identified CLEC3A, MMP7, and LCN2 known to be associated with the phosphatidylinositol‐3‐kinase/Akt pathway, as potential novel markers to predict the postoperative recurrence of PNETs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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CLEC3A, MMP7, and LCN2 as novel markers for predicting recurrence in resected G1 and G2 pancreatic neuroendocrine tumors

et al. 2019

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“…clec-2, a member of the c-type lectin family, was highly expressed in clear cell renal cell carcinoma and was positively associated with poor patient prognosis (21) and it was also observed to regulate cell proliferation and migration (22). clec3a, another c-type lectin, was reported to be highly expressed in breast invasive ductal carcinoma and promoted breast cancer cell proliferation and migration (8). a previous study has demonstrated that clec3a is involved in bone formation (23); however, the effect of clec3a on oS cells is largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Dysfunctional C-type lectins have been reported in various pathological states, including cancer; for example, Wang et al (7) observed that c-type-lectin-like-2 promoted the proliferation and migration of gastric cancer cells by regulating the aKT signaling pathway. ni et al (8) demonstrated that high expression levels of the c-type lectin domain family 3 member a (clec3a) were positively associated with poor prognosis in patients with invasive ductal carcinoma of the breast. in addition, as a member of the c-type lectin superfamily, CLEC3A was originally identified in cartilage, and a previous study reported that clec3a was involved in bone formation (6); however, the effect and molecular mechanism of clec3a in oS is largely unknown.…”

Section: Suppression Of Clec3a Inhibits Osteosarcoma Cell Proliferatimentioning

confidence: 99%

Suppression of CLEC3A inhibits osteosarcoma cell proliferation and promotes their chemosensitivity through the AKT1/mTOR/HIF1α signaling pathway

Ren¹,

Pan²,

Hou³

et al. 2020

Mol Med Report

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osteosarcoma (oS) is a primary malignant tumor that occurs in bone, and mainly affects children and adolescents. c-type lectin domain family 3 member a (clec3a) is a member of the c-type lectin superfamily, which regulates various biological functions of cells. The present study aimed to identify the effects and related mechanisms of clec3a in the proliferation and chemosensitivity of oS cells. The expression of clec3a in oS was analyzed using the Gene Expression Omnibus data profile GSE99671, and its expression in OS samples was verified using reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemical staining. The relationship between the expression of clec3a and clinical traits in patients with oS was also analyzed, including age, tumor size, TnM stage and lymph node metastasis. cell counting Kit-8 assays, colony formation assays and cell cycle distribution analysis were used to determine the roles of clec3a in the proliferation and chemosensitivity of OS cells. Finally, RT-qPCR and western blotting were used to demonstrate the relationship between clec3a and the aKT1/mTor/hypoxia-inducible factor 1-α (HiF1α) pathway. Both the mrna and protein expression levels of clec3a were increased in oS tissues compared with adjacent non-tumor tissues, and this was positively associated with TnM stage and lymph node metastasis. The genetic knockdown of clec3a with small interfering rna decreased oS cell proliferation and colony formation, and induced G1 phase arrest, whereas the overexpression of clec3a increased oS cell proliferation and colony formation, and alleviated G1 phase arrest. The suppression of clec3a also promoted enhanced the chemosensitivity of oS cells to doxorubicin (doX) and cisplatin (cddP); it also inhibited the expression of aKT1, mTor and HiF1α, further to the nuclear localization of HiF1α, and HiF1α target gene expression levels, including VeGF, GluT1 and Mcl1 were also decreased. Furthermore, treatment with the aKT activator Sc79 blocked the inhibitory effects of clec3a silencing in oS cells. in conclusion, these findings suggested that CLEC3A may function as an oncogene in oS, and that the suppression of clec3a may inhibit oS cell proliferation and promote chemosensitivity through the aKT1/mTor/HiF1α signaling pathway.

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Development of a novel prognostic signature based on single‐cell combined bulk RNA analysis in breast cancer

Xiao,

Hu,

Xie

et al. 2024

The Journal of Gene Medicine

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BackgroundBreast cancer (BC), a malignant tumor, is a significant cause of death and disability among women globally. Recent research indicates that copy number variation plays a crucial role in tumor development. In this study, we employed the Single‐Cell Variational Aneuploidy Analysis (SCEVAN) algorithm to differentiate between malignant and non‐malignant cells, aiming to identify genetic signatures with prognostic relevance for predicting patient survival.MethodsWe analyzed gene expression profiles and associated clinical data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Using the SCEVAN algorithm, we distinguished malignant from non‐malignant cells and investigated cellular interactions within the tumor microenvironment (TME). We categorized TCGA samples based on differentially expressed genes (DEGs) between these cell types. Subsequent Kyoto Encyclopedia of Genes and Genomes pathway analysis was conducted. Additionally, we developed polygenic models for the DEGs using least absolute shrinkage and selection operator‐penalized Cox regression analysis. To assess the prognostic accuracy of these characteristics, we generated Kaplan–Meier and receiver operating characteristic curves from training and validation datasets. We also monitored the expression variations of prognostic genes across the pseudotime of malignant cells. Patients were divided into high‐risk and low‐risk groups based on median risk scores to compare their TME and identify potential therapeutic agents. Lastly, polymerase chain reaction was used to validate seven pivotal genes.ResultsThe SCEVAN algorithm identified distinct malignant and non‐malignant cells in GSE180286. Cellchat analysis revealed significantly increased cellular communication, particularly between fibroblasts, endothelial cells and malignant cells. The DEGs were predominantly involved in immune‐related pathways. TCGA samples were classified into clusters A and B based on these genes. Cluster A, enriched in immune pathways, was associated with poorer prognosis, whereas cluster B, predominantly involved in circadian rhythm pathways, showed better outcomes. We constructed a 14‐gene prognostic signature, validated in a 1:1 internal TCGA cohort and external GEO datasets (GSE42568 and GSE146558). Kaplan–Meier analysis confirmed the prognostic signature's accuracy (p < 0.001). Receiver operating characteristic curve analysis demonstrated the predictive reliability of these prognostic features. Single‐cell pseudotime analysis with monocle2 highlighted the distinct expression trends of these genes in malignant cells, underscoring the intratumoral heterogeneity. Furthermore, we explored the differences in TME between high‐ and low‐risk groups and identified 16 significantly correlated drugs.ConclusionOur findings suggest that the 14‐gene prognostic signature could serve as a novel biomarker for forecasting the prognosis of BC patients. Additionally, the immune cells and pathways in different risk groups indicate that immunotherapy may be a crucial component of treatment strategies for BC patients.

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Overexpression of CLEC3A promotes tumor progression and poor prognosis in breast invasive ductal cancer

Cited by 23 publications

References 35 publications

CLEC3A, MMP7, and LCN2 as novel markers for predicting recurrence in resected G1 and G2 pancreatic neuroendocrine tumors

CLEC3A, MMP7, and LCN2 as novel markers for predicting recurrence in resected G1 and G2 pancreatic neuroendocrine tumors

Suppression of CLEC3A inhibits osteosarcoma cell proliferation and promotes their chemosensitivity through the AKT1/mTOR/HIF1α signaling pathway

Development of a novel prognostic signature based on single‐cell combined bulk RNA analysis in breast cancer

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