Fecal expression of Escherichia coli lysine decarboxylase (LdcC) is downregulated in E-cadherin negative lobular breast carcinoma.

Zs Sári,P Bai,T Kovács,Zs Karányi,P Árkosy,K Uray,M Török,I Kovács,T Csonka,É Sebő,E Mikó,J Toth,D Szeőcs,G Méhes,D Tóth,B Kiss

doi:10.1556/2060.2020.00016

Abstract

Breast cancer is characterized by oncobiosis, the abnormal composition of the microbiome in neoplastic diseases. The biosynthetic capacity of the oncobiotic flora in breast cancer is suppressed, as suggested by metagenomic studies. The microbiome synthesizes a set of cytostatic and antimetastatic metabolites that are downregulated in breast cancer, including cadaverine, a microbiome metabolite with cytostatic properties. We set out to assess how the protein expression of constitutive lysine decarboxylase (LdcC), a key enzyme for cadaverine production, changes in the feces of human breast cancer patients (n = 35). We found that the fecal expression of Escherichia coli LdcC is downregulated in lobular cases as compared to invasive carcinoma of no special type (NST) cases. Lobular breast carcinoma is characterized by low or absent expression of E-cadherin. Fecal E. coli LdcC protein expression is downregulated in E-cadherin negative breast cancer cases as compared to positive ones. Receiver operating characteristic (ROC) analysis of LdcC expression in lobular and NST cases revealed that fecal E. coli LdcC protein expression might have predictive values. These data suggest that the oncobiotic transformation of the microbiome indeed leads to the downregulation of the production of cytostatic and antimetastatic metabolites. In E-cadherin negative lobular carcinoma that has a higher potential for metastasis formation, the protein levels of enzymes producing antimetastatic metabolites are downregulated. This finding represents a new route that renders lobular cases permissive for metastasis formation. Furthermore, our findings underline the role of oncobiosis in regulating metastasis formation in breast cancer.

Highlights

Breast cancer is characterized by an altered gut [1,2,3,4,5,6,7], breast [8], oral [9], and urinary [9] microbiome
We found that the fecal expression of Escherichia coli LdcC is downregulated in lobular cases as compared to invasive carcinoma of no special type (NST) cases
Fecal expression of LdcC is low in the E-cadherin negative, lobular subtype of breast cancer

Summary

Introduction

Breast cancer is characterized by an altered gut [1,2,3,4,5,6,7], breast [8], oral [9], and urinary [9] microbiome. Changes to the microbiome can affect the immune functions of the host [15] and the microbes can modulate the behavior of the host by secreting pleiotropic metabolites These metabolites get to cancer cells through the systemic circulation [10]. The majority of the studies report lower diversity in the breast cancer oncobiome as compared to the healthy eubiome, resulting in a restricted biosynthetic capacity [3, 6, 7]. This lower biosynthetic capacity probably leads to lower production of bacterial metabolites in both the serum and the tumor. A number of antineoplastic bacterial metabolites were identified in breast cancer, including short chain fatty acids [10], lithocholic acid [7, 16] and cadaverine [6]

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