Increased claudin-4 expression is associated with poor prognosis and high tumour grade in breast cancer

Abstract Breast cancer (BC) in Africans and people of African descent is generally aggressive, with poorer prognosis and worse clinical outcomes. The molecular basis of this is however not entirely understood. The CD44+ / CD24-/low BC stem cell is known for its tumourigenic potential, tumour aggressiveness and its association with poor prognosis. This study identifies the relationship between CD44+/ CD24-/low BC stem cells and clinicopathological features of breast cancer in an African population.Methodology A Ghanaian BC cohort (n= 222) was used to assess CD44 and CD24 expression. Tissue microarray was constructed from the cohort samples and Immunohistochemically stained with CD44 and CD24 antibodies. The associations between clinicopathological features and the expression of the individual markers and their combinations were analysed. Results Of the total 222 breast cancer samples, 81.9 % were cytoplasmic CD24 positive and were associated with higher tumour grade (OR-3.623; r=0.199; p=0.004), gender (OR-9.514; p=0.028), clinical prognostic grading (OR-2.357 r= 0.162; p=0.027) and Her2 positivity (OR-0.216; r=-0.155; p=0.026). CD44 was associated with higher tumour grade (OR-3.148; r= 0.145; p-0.037), and increased mitotic count (OR-3.043, r= 0.173; p=0.028). There was no association between CD44 expression and hormone receptor status. Together, CD44+/CD24-/low staining was associated with higher tumour grade (OR-3.162; r=0.166; p=0.018), gender (OR- 12.0; p=0.012), and higher clinical prognostic staging (OR- 2.888; r=0.186; p=0.011). An inverse association of CD44+CD24+ was found with tumour grade (OR-0.220; r=-0.246; p=0.000), mitotic count (OR-0.406; r=-0.190; p=0.017) and clinical prognostic staging (OR-0.486; r=-0.151; p=0.040). There was no association between CD44-CD24+ and all the clinicopathological features.Conclusion Combined, CD44+CD24-/low was associated with poor prognosis and tumour aggression and may contribute to the tumour aggressiveness of African breast cancer. CD24 expression as a stand-alone marker was found to correlate with clinical and pathological indicators of tumour aggressiveness and poor prognosis.

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TP53 mutation and/or overexpression of the HER2 receptor are strong indicators of poor prognosis in both node-negative and node-positive early breast cancer

European Journal of Cancer ◽

10.1016/s0959-8049(02)80344-6 ◽

2002 ◽

Vol 38 (11) ◽

pp. S107-S108

Author(s):

J Alsner

Keyword(s):

Breast Cancer ◽

Early Breast Cancer ◽

Poor Prognosis ◽

Tp53 Mutation ◽

Her2 Receptor ◽

Node Negative ◽

Node Positive

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Expression intensity and localization of BAP1 in hereditary breast cancer is associated with poor prognosis

10.1055/s-0040-1717840 ◽

2020 ◽

Author(s):

V Docheva ◽

T Kolben ◽

A Koelbl ◽

E Gross ◽

A Meindl ◽

...

Keyword(s):

Breast Cancer ◽

Hereditary Breast Cancer ◽

Poor Prognosis ◽

Expression Intensity

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Targeting PKM2 promotes chemosensitivity of breast cancer cells in vitro and in vivo

Cancer Biomarkers ◽

10.3233/cbm-210111 ◽

2021 ◽

pp. 1-10

Author(s):

Yu Wang ◽

Han Zhao ◽

Ping Zhao ◽

Xingang Wang

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Cancer Cells ◽

Cancer Patients ◽

Poor Prognosis ◽

Breast Cancer Cells ◽

Breast Cancer Patients ◽

Cancer Tissues

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.

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Correction to: Cytoplasmic LXR expression is an independent marker of poor prognosis for patients with early stage primary breast cancer

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-021-03736-x ◽

2021 ◽

Author(s):

Wanting Shao ◽

Christina Kuhn ◽

Doris Mayr ◽

Nina Ditsch ◽

Magdalena Kailuwait ◽

...

Keyword(s):

Breast Cancer ◽

Primary Breast Cancer ◽

Poor Prognosis ◽

Early Stage ◽

Independent Marker

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YWHAZ interacts with DAAM1 to promote cell migration in breast cancer

Cell Death Discovery ◽

10.1038/s41420-021-00609-7 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Jie Mei ◽

Yan Liu ◽

Xinqian Yu ◽

Leiyu Hao ◽

Tao Ma ◽

...

Keyword(s):

Breast Cancer ◽

Poor Prognosis ◽

Molecular Mechanisms ◽

Transcriptional Regulator ◽

Expression Levels ◽

Functional Roles ◽

Normal Tissues ◽

Rhoa Activation ◽

Promote Cell Migration

AbstractDishevelled-associated activator of morphogenesis 1 (DAAM1) is a critical driver in facilitating metastasis in breast cancer (BrCa). However, molecular mechanisms for the regulation of DAAM1 activation are only partially elucidated. In this research, the expression levels of YWHAZ and DAAM1 were examined by immunohistochemistry (IHC) staining in BrCa tissues. The functional roles of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ)–DAAM1 axis and their regulator microRNA-613 (miR-613) in BrCa cells and associated molecular mechanisms were demonstrated in vitro. As results, the expression levels of DAAM1 and YWHAZ were significantly upregulated in BrCa tissues compared with normal tissues and remarkably associated with poor prognosis. Besides, DAAM1 and YWHAZ were positively correlated with each other in BrCa tissues. YWHAZ interacted and colocalized with DAAM1 in BrCa cells, which was essential for DAAM1-mediated microfilament remodeling and RhoA activation. Moreover, miR-613 directly targeted both YWHAZ and DAAM1, contributing to inhibiting BrCa cells migration via blocking the complex of YWHAZ–DAAM1. To sum up, these data reveal that YWHAZ regulates DAAM1 activation, and the YWHAZ–DAAM1 complex is directly targeted by the shared post-transcriptional regulator miR-613.

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Cytoplasmic LXR expression is an independent marker of poor prognosis for patients with early stage primary breast cancer

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-021-03670-y ◽

2021 ◽

Author(s):

Wanting Shao ◽

Christina Kuhn ◽

Doris Mayr ◽

Nina Ditsch ◽

Magdalena Kailuwait ◽

...

Keyword(s):

Breast Cancer ◽

Primary Breast Cancer ◽

Poor Prognosis ◽

Early Stage ◽

Clinicopathological Characteristics ◽

Clinicopathological Parameters ◽

Liver X Receptors ◽

X Receptors ◽

Independent Marker ◽

Overall Survival Analysis

Abstract Purpose The aim of this study was to investigate the expression of liver X receptors α/β (LXR) in primary breast cancer (BC) tissues and to analyze its correlations with clinicopathological parameters including patient survival. Methods In a well-characterized cohort of 305 primary BC, subcellular distribution of LXR was evaluated by immunohistochemistry. Correlations with clinicopathological characteristics as well as with patient outcome were analyzed. Results LXR was frequently localized in both nuclei and cytoplasms of BC cells, with stronger staining in nuclei. Total and nuclear LXR expression was positively correlated with ER and PR status. Overall survival analysis demonstrated that cytoplasmic LXR was significantly correlated with poor survival and appeared as an independent marker of poor prognosis, in stage I but not in stage II–III tumors Conclusion Altogether, these data suggest that cytoplasmic LXR could be defined as a prognostic marker in early stage primary BC.

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