CPNE1 predicts poor prognosis and promotes tumorigenesis and radioresistance via the AKT singling pathway in triple‐negative breast cancer

Shao, Zhihong; Ma, Xiaolong; Zhang, Yufeng; Sun, Yuanyuan; Lv, Wenjuan; He, Kuigang; Xia, Rui; Wang, Peijun; Gao, Xiaolong

doi:10.1002/mc.23177

Cited by 35 publications

(28 citation statements)

References 32 publications

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“…According to the latest American cancer statistics, breast cancer is estimated to be the most common cancer and the second most common cause of cancer-associated deaths in women [ 1 ]. Owing to higher distal metastatic and recurrent rates, triple-negative breast cancer (TNBC) patients exhibit worse overall and disease-free survival than any other type of breast cancer [ 2 – 4 ]. Etiology investigations suggest that hereditary factors account for nearly one-tenth of breast cancer cases.…”

Section: Introductionmentioning

confidence: 99%

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Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis

Wei

Zeng

et al. 2020

Cancer Cell Int

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Background: The situation faced by breast cancer patients, especially those with triple-negative breast cancer, is still grave. More effective therapeutic targets are needed to optimize the clinical management of breast cancer. Although collagen type VIII alpha 1 chain (COL8A1) has been shown to be downregulated in BRIP1-knockdown breast cancer cells, its clinical role in breast cancer remains unknown. Methods: Gene microarrays and mRNA sequencing data were downloaded and integrated into larger matrices based on various platforms. Therefore, this is a multi-centered study, which contains 5048 breast cancer patients and 1161 controls. COL8A1 mRNA expression in breast cancer was compared between molecular subtypes. In-house immunohistochemistry staining was used to evaluate the protein expression of COL8A1 in breast cancer. A diagnostic test was performed to assess its clinical value. Furthermore, based on differentially expressed genes (DEGs) and coexpressed genes (CEGs) positively related to COL8A1, functional enrichment analyses were performed to explore the biological function and potential molecular mechanisms of COL8A1 underlying breast cancer. Results: COL8A1 expression was higher in breast cancer patients than in control samples (standardized mean difference = 0.79; 95% confidence interval [CI] 0.55-1.03). Elevated expression was detected in various molecular subtypes of breast cancer. An area under a summary receiver operating characteristic curve of 0.80 (95% CI 0.76-0.83) with sensitivity of 0.77 (95% CI 0.69-0.83) and specificity of 0.70 (95% CI 0.61-0.78) showed moderate capacity of COL8A1 in distinguishing breast cancer patients from control samples. Worse overall survival was found in the higher than in the lower COL8A1 expression groups. Intersected DEGs and CEGs positively related to COL8A1 were significantly clustered in the proteoglycans in cancer and ECM-receptor interaction pathways. Conclusions: Elevated COL8A1 may promote the migration of breast cancer by mediating the ECM-receptor interaction and synergistically interplaying with DEGs and its positively related CEGs independently of molecular subtypes. Several genes clustered in the proteoglycans in cancer pathway are potential targets for developing effective agents for triple-negative breast cancer.

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Section: Introductionmentioning

confidence: 99%

“…deaths in women [1]. Owing to higher distal metastatic and recurrent rates, triple-negative breast cancer (TNBC) patients exhibit worse overall and disease-free survival than any other type of breast cancer [2][3][4]. Etiology investigations suggest that hereditary factors account for nearly one-tenth of breast cancer cases.…”

mentioning

confidence: 99%

Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis

Wei

Zeng

et al. 2020

Cancer Cell Int

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“…CPNE1 also regulates tumorigenesis and correlates with the survival of lung and prostate cancer patients. [7][8][9]24,25 However, its role in CRC is unclear. The present study showed that CPNE1 was overexpressed in CRC tissues and promoted CRC progression.…”

Section: Dovepressmentioning

confidence: 99%

CPNE1 Enhances Colorectal Cancer Cell Growth, Glycolysis, and Drug Resistance Through Regulating the AKT-GLUT1/HK2 Pathway

Wang¹,

Pan²,

Wang³

et al. 2021

OTT

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Introduction Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide. Copines-1 (CPNE1) has been shown to be overexpressed in various cancers; however, the role of CPNE1 in CRC remains unknown. Therefore, it is of great importance to elucidate the role of CPNE1 in CRC and its underlying mechanism of action. Methods CPNE1 expression in CRC tissues was measured by quantitative real-time PCR and immunohistochemical (IHC) staining. CPNE1 was knocked down (KD) or overexpressed using small inferring RNAs or lentiviral transduction in CRC cells. The proliferation, apoptosis, glycolysis, and mitochondrial respiration of CRC cells were assessed by cell counting kit-8, flow cytometry, and Xfe24 extracellular flux analyzer assays, respectively. The role of CPNE1 in tumor growth and chemoresistance was further confirmed in xenograft and patient-derived tumor xenograft models, respectively. Results CPNE1 mRNA and protein were upregulated in CRC tissues. CPNE1 promoted proliferation, inhibited apoptosis, increased mitochondrial respiration, enhanced aerobic glycolysis by activating AKT signaling, upregulated glucose transporter 1 (GLUT1) and hexokinase 2 (HK2), and downregulated the production of cleaved Caspase-3 (c-Caspase 3). CPNE1 also contributed to chemoresistance in CRC cells. CPNE1 KD inhibited tumor growth and increased the sensitivity of tumors to oxaliplatin in vivo. Conclusion CPNE1 promotes CRC progression by activating the AKT-GLUT1/HK2 cascade and enhances chemoresistance.

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“…TNBC is the BC subtype that is most aggressive and invasive. It accounts for approximately 15–20% of all breast cancer cases [ 3 ]. In comparison with other types of breast cancer, TNBC shows unfavorable prognostic features: increased frequency of visceral metastases, shorter interval without recurrence, and higher nuclear grade [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

The BIRC Family Genes Expression in Patients with Triple Negative Breast Cancer

Makuch-Kocka

Kocki

Brzozowska

et al. 2021

IJMS

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The BIRC (baculoviral IAP repeat‐containing; BIRC) family genes encode for Inhibitor of Apoptosis (IAP) proteins. The dysregulation of the expression levels of the genes in question in cancer tissue as compared to normal tissue suggests that the apoptosis process in cancer cells was disturbed, which may be associated with the development and chemoresistance of triple negative breast cancer (TNBC). In our study, we determined the expression level of eight genes from the BIRC family using the Real-Time PCR method in patients with TNBC and compared the obtained results with clinical data. Additionally, using bioinformatics tools (Ualcan and The Breast Cancer Gene-Expression Miner v4.5 (bc-GenExMiner v4.5)), we compared our data with the data in the Cancer Genome Atlas (TCGA) database. We observed diverse expression pattern among the studied genes in breast cancer tissue. Comparing the expression level of the studied genes with the clinical data, we found that in patients diagnosed with breast cancer under the age of 50, the expression levels of all studied genes were higher compared to patients diagnosed after the age of 50. We observed that in patients with invasion of neoplastic cells into lymphatic vessels and fat tissue, the expression levels of BIRC family genes were lower compared to patients in whom these features were not noted. Statistically significant differences in gene expression were also noted in patients classified into three groups depending on the basis of the Scarff-Bloom and Richardson (SBR) Grading System.

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CPNE1 predicts poor prognosis and promotes tumorigenesis and radioresistance via the AKT singling pathway in triple‐negative breast cancer

Cited by 35 publications

References 32 publications

Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis

Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis

CPNE1 Enhances Colorectal Cancer Cell Growth, Glycolysis, and Drug Resistance Through Regulating the AKT-GLUT1/HK2 Pathway

The BIRC Family Genes Expression in Patients with Triple Negative Breast Cancer

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