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      The expression of CXCL13 and its relation to unfavorable clinical characteristics in young breast cancer

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          Abstract

          Background

          Young breast cancer occupies a higher and higher proportion of breast cancer, especially in Asia, and is associated with a more unfavorable prognosis compared with the disease arising in older women. However, the poor prognosis of young breast cancer cannot be fully explained by the clinical and molecular factors.

          Methods

          This study investigated 1125 Chinese breast cancer patients diagnosed from 2009 to 2013. A data mining of gene expression profiles was performed for the young and older breast cancer patients, identifying significantly differentially expressed genes. Quantitative RT-PCR, Western blotting and immunohistochemistry assay were carried out for the clinical sample validations.

          Results

          The investigation firstly displayed that young patients (≤45 years) accounted for 47.6 % (535/1125) of breast cancer, and clinically associated with some unfavorable factors related to poor prognosis, such as invasive pathological type, high tumor grade, lymph node positive, ER negative and triple-negative subtype. Subsequently, 553 significantly differentially expressed genes were identified by the data mining. Of them, a set of genes related to immune function were observed to be up-regulated in young patients with breast cancer. Impressively, the CXCL13 (C-X-C motif chemokine 13) expression level showed the most significant difference (FC = 2.64, P = 8.2 × 10 −4). Furthermore, the validations with clinical samples and correlation analysis demonstrated that CXCL13 was indeed highly expressed in young breast cancer and closely associated with some prognostic factors including lymph node positive and ER negative.

          Conclusion

          This is the first to indicate the clinical relevance of CXCL13 to young breast cancer and represents a potential therapeutic target for young breast cancer.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12967-015-0521-1) contains supplementary material, which is available to authorized users.

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          In silico prediction of protein-protein interactions in human macrophages

          Oussema Souiai, Fatma Zahra Guerfali, Slimane Miled … (2015)
          Background: Protein-protein interaction (PPI) network analyses are highly valuable in deciphering and understanding the intricate organisation of cellular functions. Nevertheless, the majority of available protein-protein interaction networks are context-less, i.e. without any reference to the spatial, temporal or physiological conditions in which the interactions may occur. In this work, we are proposing a protocol to infer the most likely protein-protein interaction (PPI) network in human macrophages. Results: We integrated the PPI dataset from the Agile Protein Interaction DataAnalyzer (APID) with different meta-data to infer a contextualized macrophage-specific interactome using a combination of statistical methods. The obtained interactome is enriched in experimentally verified interactions and in proteins involved in macrophage-related biological processes (i.e. immune response activation, regulation of apoptosis). As a case study, we used the contextualized interactome to highlight the cellular processes induced upon Mycobacterium tuberculosis infection. Conclusion: Our work confirms that contextualizing interactomes improves the biological significance of bioinformatic analyses. More specifically, studying such inferred network rather than focusing at the gene expression level only, is informative on the processes involved in the host response. Indeed, important immune features such as apoptosis are solely highlighted when the spotlight is on the protein interaction level.
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            Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer.

            Carsten Denkert, Sibylle Loibl, Aurelia Noske … (2010)
            PURPOSE Preclinical data suggest a contribution of the immune system to chemotherapy response. In this study, we investigated the prespecified hypothesis that the presence of a lymphocytic infiltrate in cancer tissue predicts the response to neoadjuvant chemotherapy. METHODS We investigated intratumoral and stromal lymphocytes in a total of 1,058 pretherapeutic breast cancer core biopsies from two neoadjuvant anthracycline/taxane-based studies (GeparDuo, n = 218, training cohort; and GeparTrio, n = 840, validation cohort). Molecular parameters of lymphocyte recruitment and activation were evaluated by kinetic polymerase chain reaction in 134 formalin-fixed, paraffin-embedded tumor samples. Results In a multivariate regression analysis including all known predictive clinicopathologic factors, the percentage of intratumoral lymphocytes was a significant independent parameter for pathologic complete response (pCR) in both cohorts (training cohort: P = .012; validation cohort: P = .001). Lymphocyte-predominant breast cancer responded, with pCR rates of 42% (training cohort) and 40% (validation cohort). In contrast, those tumors without any infiltrating lymphocytes had pCR rates of 3% (training cohort) and 7% (validation cohort). The expression of inflammatory marker genes and proteins was linked to the histopathologic infiltrate, and logistic regression showed a significant association of the T-cell-related markers CD3D and CXCL9 with pCR. CONCLUSION The presence of tumor-associated lymphocytes in breast cancer is a new independent predictor of response to anthracycline/taxane neoadjuvant chemotherapy and provides useful information for oncologists to identify a subgroup of patients with a high benefit from this type of chemotherapy.
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              Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199.

              Sylvia Adams, Robert J Gray, Sandra Demaria … (2014)
              Recent studies suggest that tumor-infiltrating lymphocytes (TILs) are associated with disease-free (DFS) and overall survival (OS) in operable triple-negative breast cancer (TNBC). We seek to validate the prognostic impact of TILs in primary TNBCs in two adjuvant phase III trials conducted by the Eastern Cooperative Oncology Group (ECOG). Full-face hematoxylin and eosin–stained sections of 506 tumors from ECOG trials E2197 and E1199 were evaluated for density of TILs in intraepithelial (iTILs) and stromal compartments (sTILs). Patient cases of TNBC from E2197 and E1199 were randomly selected based on availability of sections. For the primary end point of DFS, association with TIL scores was determined by fitting proportional hazards models stratified on study. Secondary end points were OS and distant recurrence–free interval (DRFI). Reporting recommendations for tumor marker prognostic studies criteria were followed, and all analyses were prespecified. The majority of 481 evaluable cancers had TILs (sTILs, 80%; iTILs, 15%). With a median follow-up of 10.6 years, higher sTIL scores were associated with better prognosis; for every 10% increase in sTILs, a 14% reduction of risk of recurrence or death (P = .02), 18% reduction of risk of distant recurrence (P = .04), and 19% reduction of risk of death (P = .01) were observed. Multivariable analysis confirmed sTILs to be an independent prognostic marker of DFS, DRFI, and OS. In two national randomized clinical trials using contemporary adjuvant chemotherapy, we confirm that stromal lymphocytic infiltration constitutes a robust prognostic factor in TNBCs. Studies assessing outcomes and therapeutic efficacies should consider stratification for this parameter.
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                Author and article information

                Contributors
                Lujia Chen: Dr.Looker@hotmail.com
                Zhongxi Huang: zxhuang@smu.edu.cn
                Guangyu Yao: ygy531@163.com
                Xiaoming Lyu: lvxiaoming6108@126.com
                Jinbang Li: lzcy2008@126.com
                Xiaolei Hu: 4991132@qq.com
                Yahong Cai: choiyh@126.com
                Wenji Li: liwenji1979@163.com
                Xin Li: xinli268@gmail.com
                Changsheng Ye: yechsh2014@hotmail.com
                Journal
                Journal ID (nlm-ta): J Transl Med
                Journal ID (iso-abbrev): J Transl Med
                Title: Journal of Translational Medicine
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1479-5876
                Publication date (Electronic): 20 May 2015
                Publication date PMC-release: 20 May 2015
                Publication date Collection: 2015
                Volume: 13
                Electronic Location Identifier: 168
                Affiliations
                [ ]Breast Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515 People’s Republic of China
                [ ]Cancer Research Institute and the Provincial Key Laboratory of Functional Proteomics, Southern Medical University, Guangzhou, Guangdong 510515 People’s Republic of China
                [ ]Department of Laboratory Medicine, the Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong 510630 People’s Republic of China
                Article
                Publisher ID: 521
                DOI: 10.1186/s12967-015-0521-1
                PMC ID: 4471911
                PubMed ID: 25990390
                SO-VID: 80b10882-9ba6-4fd0-babd-1b1ec0d1ee84
                Copyright © © Chen et al. 2015
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 9 November 2014
                Date accepted : 6 May 2015
                Categories
                Subject: Research
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                issue-copyright-statement © The Author(s) 2015

                ScienceOpen disciplines: Medicine
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                ScienceOpen disciplines: Medicine

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