Dachshund 1 is Differentially Expressed Between Male and Female Breast Cancer: A Matched Case-Control Study of Clinical Characteristics and Prognosis

Cui, Qiuxia; Kong, Deguang; Li, Zhihua; Ahiable, Philemon; Wang, Kun; Wu, Zeyu; Wu, Gaosong

doi:10.1016/j.clbc.2018.01.011

Cited by 5 publications

(5 citation statements)

References 36 publications

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“…suppression of tumorigenesis via p53 up-regulation, via SIX1 inhibition, and DACH1 upregulation, might be valid for males only while in females SIX1 could act via other mechanisms. Accordingly, a contrasting gene expression pattern comparable to our results was shown in male and female breast cancer ( 28 ). In this study, DACH1 and SIX1 had contrasting expression pattern in males and females and comparable opposite prognostic implication.…”

Section: Discussionsupporting

confidence: 88%

Upregulation of the oestrogen target gene SIX1 is associated with higher growth speed and decreased survival in HCV‑positive women with hepatocellular carcinoma

et al. 2022

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The male/female ratio of patients with hepatocellular carcinoma (HCC) is often unbalanced towards the male sex, indicating a sex predisposition for HCC development. A possible explanation may be attributed to different hormonal statuses, including the pro-inflammatory action of androgens in men and the protective effects of oestrogen against excessive inflammation in women. Although several studies have studied gene expression in patients with HCC, very few have attempted to identify features that could be distinctive between male and female patients. The present study aimed to identify distinctive signalling mechanisms between men and women that may be associated with HCC progression. The present study analysed a detailed microarray database that was obtained from the prospective study of 78 patients with HCC to study gene expression according to sex. In addition, the present study aimed to evaluate whether the differentially expressed genes were known oestrogen targets. Moreover, RNAs from the HCC cohort were evaluated for microRNA (miRNA/miR) expression, and a relationship between miRNA and gene expression according to sex was investigated.One gene, sineoculis homeobox homolog 1 (SIX1), which is known to be an oestrogen target gene, was revealed to be highly upregulated in hepatitis virus C (HCV)-positive female patients with HCC but not in HCV-positive male patients. In addition, SIX1 upregulation had a significant relationship with tumour growth speed (assessed as tumour doubling time in two CTs performed 6 weeks apart) and survival (P=0.009 and P=0.042, respectively) in female patients only. Furthermore, SIX1 upregulation was related with miR-421 and miR-9-5p only in male patients; however, in female patients, SIX1 upregulation had a direct relationship with miR-181b, miR-503-5p and miR-125b (miRNAs with potential oncogenic capacity), and an inverse correlation with miR139-5p, miR-26b, let7c-3p and let7c-5p (putatively oncosuppressive microRNAs). These data suggested a distinctive model for liver carcinogenesis in HCV-positive women, with downregulation of protective mechanisms against tumour progression and the activation of potential oncogenes, in relation to the oestrogen target gene SIX1. (IRB10/08_CE_UniRer; ClinicalTrials ID: NCT01657695).

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Section: Discussionsupporting

confidence: 88%

Upregulation of the oestrogen target gene SIX1 is associated with higher growth speed and decreased survival in HCV‑positive women with hepatocellular carcinoma

et al. 2022

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“…In the survival analysis, high DACH1 expression was markedly associated with worse prognosis, indicating that DACH1 may serve as a potential prognostic marker of poor prognosis in CRC. However, some studies in non-intestinal cell types have identified an antiproliferative role for DACH1 [7,20], suggesting that DACH1 may play different roles depending on the cell type and/or context. Interestingly, a recent research found out that DACH1 was expressed less in male breast cancer than in female breast cancer [21].…”

Section: Discussionmentioning

confidence: 99%

“…However, some studies in non-intestinal cell types have identified an antiproliferative role for DACH1 [7,20], suggesting that DACH1 may play different roles depending on the cell type and/or context. Interestingly, a recent research found out that DACH1 was expressed less in male breast cancer than in female breast cancer [21]. In our study, the percentage of female patients that express high level of DACH1 was found to be higher than male patients even the statistical significance is not reached (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Organoid modelling identifies that DACH1 functions as a tumour promoter in colorectal cancer by modulating BMP signalling

Zhang

et al. 2020

EBioMedicine

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Background: Dachshund homologue 1 (DACH1) is highly expressed in LGR5+ intestinal stem cells and colorectal tumours. However, the roles of DACH1 in intestinal cell stemness and colorectal tumorigenesis remain largely undefined. Methods: We used immunohistochemistry, western blotting and quantitative real-time PCR to analyse DACH1 expression in colorectal cancer (CRC) samples. CRISPR/Cas9 gene editing and lentiviral vector-mediated overexpression and shRNA-mediated knockdown of DACH1 were utilized to modulate DACH1 expression in cell lines and organoids. An intestinal organoid-based functional model was analysed, and cancer cell colony formation, sphere formation assays and murine xenotransplants were performed to reveal the role of DACH1 in CRC cell proliferation, stemness and tumorigenesis. Immunofluorescence, co-immunoprecipitation, RNA interference and microarray data analyses were conducted to demonstrate the association between DACH1 and the bone morphogenetic protein (BMP) signalling pathway. Findings: DACH1 is specifically expressed in discrete crypt base cells, and increased DACH1 expression was found in all stages of CRC. Moreover, the high expression of DACH1 independently predicted poor prognosis. In colon cancer cells, shRNA-mediated suppression of DACH1 inhibited cell growth in vitro and in vivo. By studying the intestinal organoid-based functional model, we found that depletion of DACH1 reduced the organoid formation efficiency and tumour organoid size. DACH1 overexpression stimulated both colonsphere formation and tumour organoid formation in the context of dysregulated BMP signalling. Mechanistic characterizations indicated that overexpression of DACH1 affects a subset of stem cell signature genes implicated in stem cell proliferation and maintenance through the suppression of BMP signalling via SMAD4. Interpretation: Together, our study highlights DACH1 as an integral regulator of BMP signalling during intestinal tumorigenesis, and DACH1 could be a potential prognostic marker and therapeutic target for colorectal cancer patients.

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“…Thus, MBC represents less than 1% of all BC cases, accounting for 0.11% of all male neoplasms [26]. Usually, patients with MBC have it detected at an advanced stage at the time of diagnosis, are at an older age, and have a worse overall survival (OS) rate compared to FBC patients [106], so MBC mortality is higher (18.2%) than FBC (17.2%) [107]. Moreover, Zeinomar et al (2021) showed that Black men have worse overall survival following a BC diagnosis compared to White men [108].…”

Section: Biological Sex-and Gender-related Disparity In Breast Cancermentioning

confidence: 99%

“…The cytoplasmic DDX3 overexpression was associated with androgen expression receptor (AR), so cytoplasmic DDX3 expression could be a useful prognosticator in MBC [124]. Cui et al (2018) showed that DACH1, which is expressed widely in normal adult tissues and functions as a tumor suppressor in a variety of neoplasms [125], is differentially expressed between MBC and FBC, concluding that the DACH1 gene was downregulated in MBC and HER2 was overexpressed in FBC [107].…”

Section: Biological Sex-and Gender-related Disparity In Breast Cancermentioning

confidence: 99%

Biological Basis of Breast Cancer-Related Disparities in Precision Oncology Era

Neagu,

Bruno,

Johnson

et al. 2024

IJMS

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Precision oncology is based on deep knowledge of the molecular profile of tumors, allowing for more accurate and personalized therapy for specific groups of patients who are different in disease susceptibility as well as treatment response. Thus, onco-breastomics is able to discover novel biomarkers that have been found to have racial and ethnic differences, among other types of disparities such as chronological or biological age-, sex/gender- or environmental-related ones. Usually, evidence suggests that breast cancer (BC) disparities are due to ethnicity, aging rate, socioeconomic position, environmental or chemical exposures, psycho-social stressors, comorbidities, Western lifestyle, poverty and rurality, or organizational and health care system factors or access. The aim of this review was to deepen the understanding of BC-related disparities, mainly from a biomedical perspective, which includes genomic-based differences, disparities in breast tumor biology and developmental biology, differences in breast tumors’ immune and metabolic landscapes, ecological factors involved in these disparities as well as microbiomics- and metagenomics-based disparities in BC. We can conclude that onco-breastomics, in principle, based on genomics, proteomics, epigenomics, hormonomics, metabolomics and exposomics data, is able to characterize the multiple biological processes and molecular pathways involved in BC disparities, clarifying the differences in incidence, mortality and treatment response for different groups of BC patients.

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Dachshund 1 is Differentially Expressed Between Male and Female Breast Cancer: A Matched Case-Control Study of Clinical Characteristics and Prognosis

Cited by 5 publications

References 36 publications

Upregulation of the oestrogen target gene SIX1 is associated with higher growth speed and decreased survival in HCV‑positive women with hepatocellular carcinoma

Upregulation of the oestrogen target gene SIX1 is associated with higher growth speed and decreased survival in HCV‑positive women with hepatocellular carcinoma

Organoid modelling identifies that DACH1 functions as a tumour promoter in colorectal cancer by modulating BMP signalling

Biological Basis of Breast Cancer-Related Disparities in Precision Oncology Era

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