Potential biomarkers of ductal carcinoma in situ progression

Dettogni, Raquel Spinassé; Stur, Elaine; Laus, Ana Carolina; Vieira, René Aloísio da Costa; Marques, Márcia Maria Chiquitelli; Santana, Iara Viana Vidigal; Pulido, José Zago; Ribeiro, Laura Fregonassi; Parmanhani, Narelle de Jesus; Agostini, Lidiane Pignaton; Reis, Ruth; Santos, Eldamária de Vargas Wolfgramm dos; Alves, Lyvia Neves Rebello; García, Francisco Debesa; Santos, Javíer; Ventorim, Diego do Prado; Reis, Rui Manuel; Louro, Iúri Drumond

doi:10.1186/s12885-020-6608-y

Cited by 21 publications

(26 citation statements)

References 33 publications

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“…After a 5year follow up, the primary tumors were analyzed in a first step with the "PanCancer Progression Panel" from NanoString. This panel has been shown previously to comprehensively characterize genes involved in tumor progression and metastasis of solid tumors [19,20]. Subsequently, the multidimensional PCA revealed a distinct expression pattern of the analyzed genes throughout the defined groups and the most homogenously expressed gene was CIB1.…”

Section: Discussionmentioning

confidence: 92%

Expression of CIB1 correlates with colorectal liver metastases but not with peritoneal carcinomatosis

et al. 2021

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Background Molecular differences in colorectal cancer (CRC) are associated with the metastatic route. Patient survival is mainly driven by metastatic spread thus it is imperative to understand its key drivers to develop biomarkers for risk stratification, follow-up protocols and personalized therapy. Thus, this study aimed to identify genes associated with the metastatic route in CRC. Material and methods CRC patients resected at our clinic from 2005 to 2014 and with a minimum 5-year follow-up were included in this analysis and grouped into CRC with hepatic (HEP), peritoneal (PER) or without distant metastases (M0), and HEP/PER. Firstly, tumor RNA of 6 patients each was isolated by microdissection from formalin-fixed paraffin-embedded specimens and analyzed by a NanoString analysis. Subsequently, these results were validated with immunohistochemistry and correlated to clinicopathological parameters in a larger collective of CRC patients (HEP n = 51, PER n = 44, M0 n = 47, HEP/PER n = 28). Results Compared to M0, HEP tumors showed 20 differentially expressed genes associated with epithelial-mesenchymal transition (EMT) and angiogenesis. Compared to M0, PER tumors had 18 differentially expressed genes. The finding of different gene signatures was supported by the multidimensional principal component clustering analysis. Tumor perforation did not influence the metastatic route. CIB1 was homogenously and significantly overexpressed in HEP compared to M0 (p < 0.001), but not in PER. Furthermore, immunohistochemical validation demonstrated that the mean CIB1 expression in HEP was 80% higher than in M0 (p < 0.001). Conclusion Gene expression analysis revealed that CIB1 is significantly overexpressed in CRC leading to liver metastases compared to M0 and PER. Thus, the present results suggest that CIB1 may play a crucial role for hematogenous spread to the liver but not for peritoneal carcinomatosis. Consequently, CIB1 seems to be a promising prognostic marker and a potential tool for future targeted therapies as well as early diagnostics and follow-up.

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Section: Discussionmentioning

confidence: 92%

Expression of CIB1 correlates with colorectal liver metastases but not with peritoneal carcinomatosis

et al. 2021

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“…Although we have proposed possible progression markers that will require more extensive validation, it still remains to be seen whether, and how, each of these may play a role in this disease. A recent study 7 also looking at potential biomarkers of DCIS progression, identified the genes FGF2 , GAS1 and SFRP1 as being markers of in situ progression, suggesting their downregulation contributed to the invasiveness of epithelial cells. In support of this we also see that these 3 genes are notably down regulated as samples are arrayed along the timeline.…”

Section: Resultsmentioning

confidence: 99%

“…2A). Gene Ontology (GO) term analysis on these two networks revealed an enrichment for upregulated (in IDC over DCIS) genes involved in both extracellular matrix (EM) organisation Fold Enrichment;29) and cell adhesion (FDR 1.8E-6, Fold Enrichment; 7) and down-regulated genes associated with both epidermis development Fold Enrichment;18) and epithelial development Fold Enrichment;7). Specific genes included in each cluster network are frequently associated with these processes, such as FN1 (Fibronectin) and the collagen genes (COL1A2, COL1A1, COL12A, COL3A1, COL5A2).…”

Section: Two Gene Network Dominate Expression Differences Between Co-...mentioning

confidence: 99%

Creating a ‘Timeline’ of ductal carcinoma in situ to identify processes and biomarkers for progression towards invasive ductal carcinoma

Rebbeck

Jian

Bornelöv

et al. 2022

Preprint

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Ductal carcinoma in situ (DCIS) is considered a non-invasive precursor to breast cancer, and although associated with an increased risk of developing invasive disease, many women with DCIS will never progress beyond their in situ diagnosis. The path from normal duct to invasive disease is not well understood, and efforts to do so are hampered by the substantial heterogeneity that exists between patients and even within patients. Using gene expression analysis, we have generated a ‘Timeline’ of disease progression, utilising the variability within patients and combining >2,000 individually micro-dissected ductal lesions from 145 patients into one continuous trajectory. Using this Timeline we show there is a progressive loss in basal layer integrity, coupled with two epithelial to mesenchymal transitions (EMT), one early in the timeline and a second just prior to cells leaving the duct. We identify early processes and potential biomarkers, including CAMK2N1, MNX1, ADCY5, HOXC11 and ANKRD22, whose reduced expression is associated with the progression of DCIS to invasive breast cancer.

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“…2 The intervention of breast precancerous lesions and blocking its development to breast cancer is the key to the prevention and treatment of breast cancer. 8 Xihuang Pill (XHP) is a traditional Chinese herbal formula, which is published in "waike zhengzhi quansheng ji". It consists of NIU HUANG, SHE XIANG, RU XIANG (vinegar), and MO YAO (vinegar).…”

Section: Introductionmentioning

confidence: 99%

“… 2 The intervention of breast precancerous lesions and blocking its development to breast cancer is the key to the prevention and treatment of breast cancer. 8 …”

Section: Introductionmentioning

confidence: 99%

Based on BATMAN-TCM to Explore the Molecular Mechanism of Xihuang Pill Regulating Immune Function to Treat Breast Precancerous Lesions

Li¹,

Fan²,

Dong³

et al. 2021

BCTT

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Objective:The specific mechanism of Xihuang Pill in the treatment of breast precancerous lesions and breast cancer has not yet been elucidated. Methods: In our study, BATMAN-TCM (a Bioinformatics Analysis Tool for Molecular mechanisms of Traditional Chinese Medicine) was used to forecast the relationship among chemical components, immune targets, and diseases of each herb in Xihuang Pill and constructed a component-target-disease network. Taking breast precancerous lesion model rats as the research object, the molecular mechanism of Xihuang Pill regulating immunity was analyzed. Results: BATMAN-TCM prediction showed that 309 genes were enriched in the biological process of "immune system response", which was the target of Xihuang Pill to regulate the immune system. The target of breast cancer disease and the genes related to Xihuang Pill's immune system response were crossed, and 88 cross genes were obtained. According to the enrichment results of GO/KEGG pathway, T cell activation was found to be the most relevant. We select Th1 cells (IL-2, IFN-γ) and Th2 cells (IL-4, IL-10) among them for animal experiment verification. The results show that Xihuang Pill can upregulate the serum IFN-γ and IL-2 levels, reduce the IL-4 and IL-10 levels, and regulate the balance of Th1/Th2 cells in the peripheral blood of rats with breast precancerous lesions. Conclusion: Xihuang Pill targets a variety of immune-related molecules related to breast precancerous lesions and is a traditional Chinese medicine formula that effectively regulates immune function.

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Potential biomarkers of ductal carcinoma in situ progression

Cited by 21 publications

References 33 publications

Expression of CIB1 correlates with colorectal liver metastases but not with peritoneal carcinomatosis

Expression of CIB1 correlates with colorectal liver metastases but not with peritoneal carcinomatosis

Creating a ‘Timeline’ of ductal carcinoma in situ to identify processes and biomarkers for progression towards invasive ductal carcinoma

Based on BATMAN-TCM to Explore the Molecular Mechanism of Xihuang Pill Regulating Immune Function to Treat Breast Precancerous Lesions

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