Bioinformatics analysis of prognostic significance of COL10A1 in breast cancer

Zhang, Mingdi; Chen, Hongliang; Wang, Maoli; Bai, Fang; Wu, Kangning

doi:10.1042/bsr20193286

Cited by 40 publications

(33 citation statements)

References 21 publications

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“…There is sufficient evidence to support the role of COL10A1 in the diagnosis and prognosis of breast cancer, but more basic experiments on its functionary mechanism are still urgently needed for further research and demonstration [ 10 ]. High COL10A1 expression is significantly correlated with worse OS, RFS, DFS, and DMFS [ 10 ]. COL10A1 is highly expressed in tumor tissues of breast cancer patients, according to the GEPIA repository ( http://gepia.cancer-pku.cn/ ).…”

Section: Discussionmentioning

confidence: 99%

“…Interesting, COL10A1 has been confirmed to be overexpressed in different subtypes of breast cancer. Besides, it is documented that higher expression of COL10A1 in breast cancer patients is closely related to worse overall survival (OS), relapse-free survival (RFS), disease-free survival (DFS), and distant metastasis-free survival (DMFS) [ 10 ]. Therefore, we investigated COL10A1 as a potential therapeutic target for breast cancer.…”

Section: Introductionmentioning

confidence: 99%

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Collagen Type X Alpha 1 (COL10A1) Contributes to Cell Proliferation, Migration, and Invasion by Targeting Prolyl 4-Hydroxylase Beta Polypeptide (P4HB) in Breast Cancer

Yang

Zhang

2020

Med Sci Monit

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Background Breast cancer, a common malignant tumor, has been considered as the leading cause of cancer-related death in women. Collagen type X alpha 1 (COL10A1) is overexpressed in breast cancer. The current study was designed to determine the functional involvement and regulatory mechanism of COL10A1 on the growth and metastasis of breast cancer. Material/Methods COL10A1 and Prolyl 4-hydroxylase beta polypeptide (P4HB) expressions in normal tissues and tumor tissues of breast cancer patients were obtained from the GEPIA dataset. COL10A1 and P4HB levels in breast cancer cell lines were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Furthermore, the interaction between COL10A1 and P4HB was confirmed by co-immunoprecipitation (Co-IP) assay. Cell Counting Kit-8 (CCK-8) and colony formation assay were applied to evaluate cell proliferation and clone-forming abilities of breast cancer cells. In addition, wound healing assay and transwell assay were performed to measure cell migration and invasion capabilities, respectively, in breast cancer. Results The GEPIA dataset presented overexpressed COL10A1 and P4HB in tumor tissues of breast cancer patients. COL10A1 and P4HB expression levels were greatly upregulated in breast cancer cell lines. In addition, COL10A1 could directly interact with P4HB. Functionally, overexpressed COL10A1 boosted the proliferation and metastasis of breast cancer cells and silenced COL10A1 impeded the progression of breast cancer. More importantly, knockdown of P4HB weakened the promoting effects of overexpressed COL10A1 on cell proliferation, migration, and invasion in breast cancer. Conclusions COL10A1 promotes the malignant progression of breast cancer by upregulating P4HB expression, indicating that COL10A1 functions as an oncogene in breast cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Collagen Type X Alpha 1 (COL10A1) Contributes to Cell Proliferation, Migration, and Invasion by Targeting Prolyl 4-Hydroxylase Beta Polypeptide (P4HB) in Breast Cancer

Yang

Zhang

2020

Med Sci Monit

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“…COL10A1, COL1A1, and MFAP2 are constituents of the extracellular matrix remodeling, which is an important process in breast tumor invasion and tumor cell dissemination ( McSherry et al, 2007 ). Overexpression of the genes encoding these proteins is associated with poor breast cancer survival, and MFAP2 has been shown to promote cell proliferation, migration, invasion, and epithelial to mesenchymal transition ( Wang et al, 2018 ; Liu et al, 2018 ; Zhang et al, 2020 ). MMP11 is a proteinase that is involved in extracellular matrix degradation directly by degrading collagen IV and indirectly by inhibiting the alpha1-proteinase inhibitor ( Pan et al, 2003 ; Motrescu et al, 2008 .…”

Section: Discussionmentioning

confidence: 99%

Multi-Omics Marker Analysis Enables Early Prediction of Breast Tumor Progression

Lien

Bergholtz

et al. 2021

Front. Genet.

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Ductal carcinoma in situ (DCIS) is a preinvasive form of breast cancer with a highly variable potential of becoming invasive and affecting mortality of the patients. Due to the lack of accurate markers of disease progression, many women with detected DCIS are currently overtreated. To distinguish those DCIS cases who are likely to require therapy from those who should be left untreated, there is a need for robust and predictive biomarkers extracted from molecular or genetic profiles. We developed a supervised machine learning approach that implements multi-omics feature selection and model regularization for the identification of biomarker combinations that could be used to distinguish low-risk DCIS lesions from those with a higher likelihood of progression. To investigate the genetic heterogeneity of disease progression, we applied this approach to 40 pure DCIS and 259 invasive breast cancer (IBC) samples profiled with genome-wide transcriptomics, DNA methylation, and DNA copy number variation. Feature selection using the multi-omics Lasso-regularized algorithm identified both known genes involved in breast cancer development, as well as novel markers for early detection. Even though the gene expression-based model features led to the highest classification accuracy alone, methylation data provided a complementary source of features and improved especially the sensitivity of correctly classifying DCIS cases. We also identified a number of repeatedly misclassified DCIS cases when using either the expression or methylation markers. A small panel of 10 gene markers was able to distinguish DCIS and IBC cases with high accuracy in nested cross-validation (AU-ROC = 0.99). The marker panel was not specific to any of the established breast cancer subtypes, suggesting that the 10-gene signature may provide a subtype-agnostic and cost-effective approach for breast cancer detection and patient stratification. We further confirmed high accuracy of the 10-gene signature in an external validation cohort (AU-ROC = 0.95), profiled using distinct transcriptomic assay, hence demonstrating robustness of the risk signature.

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“…14,15 LRRC15 overexpression is quite specific for malignancy as it tends to be restricted to solid tumors and their cancer-associated stromal fibroblasts while sparing normal host tissue. [16][17][18] This overexpression has been shown to promote metastasis and progression in breast cancer, ovarian cancer, and soft tissue sarcomas. 15,18,19 As a transmembrane protein, LRRC15 has been reported as a robust and emerging therapeutic target for cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

“…This family of proteins generally regulates a broad repertoire of functions, including cell adhesion, invasion, immune response, apoptosis, autophagy, extracellular matrix assembly, RNA processing, and neuronal development 14,15 . LRRC15 overexpression is quite specific for malignancy as it tends to be restricted to solid tumors and their cancer‐associated stromal fibroblasts while sparing normal host tissue 16–18 . This overexpression has been shown to promote metastasis and progression in breast cancer, ovarian cancer, and soft tissue sarcomas 15,18,19 .…”

Section: Introductionmentioning

confidence: 99%

Expression and clinical implications of leucine‐rich repeat containing 15 (LRRC15) in osteosarcoma

Cui

Dean²,

Wei³

et al. 2020

Journal Orthopaedic Research

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Leucine-rich repeat containing 15 (LRRC15) is a member of the leucine-rich repeat superfamily that is overexpressed in various cancers and associated with higher tumor grade and aggression. Despite its known tumorigenicity, its roles within osteosarcoma are unknown, prompting us to evaluate its expression and clinical significance within this rare yet aggressive cancer. Western blots showed differential expression of LRRC15 in the osteosarcoma cell lines MNNG/HOS, KHOS, 143B, MG63, Saos-2, and U2OS. We additionally validated this positive expression, as well as sublocalization to the cell membrane, with immunofluorescence. A tissue microarray constructed from 69 osteosarcoma patient tissues was immunohistochemically stained for LRRC15 expression, stratified, and used for clinicopathological analysis. Publicly available databases on LRRC15 expression, including RNA sequencing data from the Therapeutically Applicable Research to Generate Effective Treatments on Osteosarcoma (TARGET-OS) and the Gene Expression database of Normal and Tumor tissues 2 (GENT2) were also analyzed. We found 63 of the 69 (91.3%) patient tissues exhibited some degree of LRRC15 immunostaining, including no staining (6 of 69, 8.7%), 1+ staining (12 of 69, 17.4%), 2+ staining (25 of 69, 36.2%), and 3+ staining (26 of 69, 37.7%). The patients with osteosarcomas having elevated LRRC15 expression demonstrated comparatively increased metastasis, chemoresistance, and shorter 5-year survival rates. Our analysis of the TARGET-OS and GENT2 databases also showed increased LRRC15 gene expression in osteosarcoma. Taken together, our study supports LRRC15 as a prognostic biomarker and emerging therapeutic target in osteosarcoma.

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Bioinformatics analysis of prognostic significance of COL10A1 in breast cancer

Cited by 40 publications

References 21 publications

Collagen Type X Alpha 1 (COL10A1) Contributes to Cell Proliferation, Migration, and Invasion by Targeting Prolyl 4-Hydroxylase Beta Polypeptide (P4HB) in Breast Cancer

Collagen Type X Alpha 1 (COL10A1) Contributes to Cell Proliferation, Migration, and Invasion by Targeting Prolyl 4-Hydroxylase Beta Polypeptide (P4HB) in Breast Cancer

Multi-Omics Marker Analysis Enables Early Prediction of Breast Tumor Progression

Expression and clinical implications of leucine‐rich repeat containing 15 (LRRC15) in osteosarcoma

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