Gene Expression Profiles for Recurrence of Lymph Node-positive Primary Breast Cancer in Women Over 40 Years of Age

Abstract Background: Specific gene expression profiles correlate with recurrence of breast cancer in lymph node-negative patients. In contrast, insufficient knowledge is available regarding tumor-specific gene expression in patients with lymph node metastasis before surgery. Furthermore, such patients experience cumulative incidences of relapse greater than 50%. Methods: Sections of formalin-fixed paraffin embedded (FFPE) were prepared from breast tumors of 37 patients who were followed for at least 5 years. FFPE samples of patients with recurrent ductal breast cancer (n = 25) and 12 FFPE samples of such patients without recurrence were subjected to microarray analysis to identify gene expression profiles specifically associated with positive lymph nodes confirmed during surgery that were accompanied by lymphocytic invasion. Immunohistochemistry was employed to determine the estrogen receptor (ER) status of cancer tissues. All patients were administered tamoxifen after surgery, and this treatment continued for more than 5 years, or until cancer recurred. This strategy eliminated interactions between different therapeutics as potential confounding factors that influenced patients' outcomes.Results: Sixteen genes were expressed at significantly higher levels in patients with ER-positive (+) breast cancer with recurrence compared with those without recurrence. Gene Set Enrichment Analysis of The Kyoto Encyclopedia of Genes and Genomes (KEGG) identified 73 genes encoding olfactory receptors included in the “Olfactory transduction” pathway that were enriched in the ER+ recurrence group (FDR P < 0.05). The KEGG “Histidine metabolism” and “Retinol metabolism” pathways were enriched in patients with ER-negative (–) breast cancer with recurrence (FDR P < 0.05). Conclusions: The present study is the first, to our knowledge, to identify 16 genes encoding proteins with diverse functions as well as 73 genes encoding olfactory receptors. These genes may serve as presurgical biomarkers for the recurrence of ER+ breast cancers with lymph node metastasis before surgery. These findings identify potential therapeutic targets for preventing cancer relapse, particularly after lymph nodes metastasis.

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Prediction of Lymph Node Metastasis with Use of Artificial Neural Networks Based on Gene Expression Profiles in Esophageal Squamous Cell Carcinoma

Annals of Surgical Oncology ◽

10.1245/aso.2004.03.007 ◽

2004 ◽

Vol 11 (12) ◽

pp. 1070-1078 ◽

Cited By ~ 39

Author(s):

Takatsugu Kan ◽

Yutaka Shimada ◽

Fumiaki Sato ◽

Tetsuo Ito ◽

Kan Kondo ◽

...

Keyword(s):

Gene Expression ◽

Neural Networks ◽

Squamous Cell Carcinoma ◽

Artificial Neural Networks ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Esophageal Squamous Cell Carcinoma ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Node Metastasis

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2–20 Gene-Expression Profiles to Predict Distant Metastasis of Lymph-Node-Negative Primary Breast Cancer

Breast Diseases A Year Book Quarterly ◽

10.1016/s1043-321x(06)80430-3 ◽

2006 ◽

Vol 17 (2) ◽

pp. 154-155 ◽

Cited By ~ 2

Author(s):

D.F. Hayes

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Lymph Node ◽

Distant Metastasis ◽

Primary Breast Cancer ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Node Negative

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Prediction of lymph node metastasis by analysis of gene expression profiles in non-small cell lung cancer1

Journal of Surgical Research ◽

10.1016/j.jss.2004.06.002 ◽

2004 ◽

Vol 122 (1) ◽

pp. 61-69 ◽

Cited By ~ 21

Author(s):

Minoru Takada ◽

Mitsuhiro Tada ◽

Eiji Tamoto ◽

Akiko Kawakami ◽

Katsuhiko Murakawa ◽

...

Keyword(s):

Gene Expression ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Small Cell ◽

Small Cell Lung ◽

Node Metastasis

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Ancestry-specific gene expression profiles in TNBC tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.1547 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 1547-1547

Author(s):

Windy Marie Dean-Colomb ◽

Rachel Martini ◽

Akanksha Verma ◽

Jason White ◽

Olivier Elemento ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Clinical Outcomes ◽

Expression Profiles ◽

African Ancestry ◽

Tumor Biology ◽

Gene Expression Profiles ◽

Specific Gene ◽

Expression Levels ◽

Specific Gene Expression

1547 Background: Due to persistent disparities in breast cancer mortality, there has been a renewed focus on investigating tumor biology. Deeper exploration has exposed distinctions in tumor biology based upon self-reported race and ancestry. The disparities associated with Triple Negative Breast Cancer (TNBC) across the modern African Diaspora suggests that there is a genetic ancestry connection between its aggressive tumor biology and clinical outcomes. Understanding this connection could hold the key to improving clinical outcomes in this group. Methods: We investigated 75 TNBC primary tumors using Self-Reported Race (SRR) groups: African American (AA, n = 42) and European American (EA, n = 33). Using best practices established by TCGA, we analyzed bulk RNA sequencing to measure changes in genome-wide expression levels. We next quantified global ancestry in a novel manner using RNAseq variants using 1000 Genomes as the reference data. We then identified African and European ancestry-associated genes using a logistic regression (adjusted FDR p < 0.05) between quantified ancestry and gene expression levels. Results: We identified > 150 genes associated with quantified African ancestry. We also found using quantified ancestry was a more robust method to screen for differentially expressed genes than SRR. Using an updated TNBC subtyping method, we noted higher incidences of Basal-like 2 tumors in AAs. Pathway analyses indicated several canonical cancer pathways; including, TP53, NFKB1 and AKT, have altered functionality in patients of African descent. For example, TP53-associated genes were activated in TNBC tumors of AA versus EA. This upregulation, rather than loss of function, is suggestive of polymorphic and/or ancestry-specific expression regulation, likely driven by population-private genetic variants. Lastly, we used TCGA data to validate a subset of African ancestry-specific genes that were upregulated in AA patients in our cohort. Specifically, PIM3, ZBTB22 and PPP2R4 each retained significant upregulation, in our cohort, but also TNBC tumors from TCGA (p = 0.0018, 0.023 and 0.022, respectively). Conclusions: Our study has uncovered ancestry-specific gene expression profiles in TNBC tumors. The distinct distribution of TNBC subtypes and altered functional oncologic pathways are evidence that biological underpinnings in TNBC can be driven by shared genetic ancestry. These findings emphasize the need to investigate patient populations of various ancestral origins in order to fully appreciate the molecular diversity in tumor biology for precision of disease management.

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Gene Expression of Mesenchyme Forkhead 1 (FOXC2) Significantly Correlates With the Degree of Lymph Node Metastasis in Colorectal Cancer

International Surgery ◽

10.9738/1399.1 ◽

2011 ◽

Vol 96 (3) ◽

pp. 207-216 ◽

Cited By ~ 19

Author(s):

Toshiaki Watanabe ◽

Takashi Kobunai ◽

Yoko Yamamoto ◽

Keiji Matsuda ◽

Soichiro Ishihara ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Lymph Node Metastases ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Node Metastasis ◽

Node Metastases ◽

Colorectal Cancer Patients

Abstract In stage III colorectal cancer, patients with N1 stage tumors show poorer outcome than patients with N2 stage tumors. Our objective was to identify genes that are predictive for the presence of lymph node metastasis, and to characterize the aggressiveness of lymph node metastases. Gene expression profiles of colorectal cancer were determined by microarray in training (n = 116) and test (n = 25) sets of patients. We identified 40 discriminating probes in patients with and without lymph node metastases. Using these probes, we could predict the presence of lymph node metastasis with an accuracy of 87.1% (training set) and 76.0% (test set). Among discriminating probes, FOXC2 expression was significantly correlated with the degree of lymph node metastasis. FOXC2 was expressed significantly and disparately in patients with N1 and N2 stage tumors as analyzed by real-time reverse transcriptase–polymerase chain reaction. FOXC2 appears to be involved in determining the aggressiveness of lymph node metastasis in colorectal cancer.

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