High-level TNFSF13 predict a good response to post-operative chemotherapy in patients with basal-like breast cancer: A systematic review 林惠鈺1,2 歸家豪1,3 李薰華1,4,5,7 邱惠雯1,6 蕭宏昇8 林源峰1* 1台北醫學大學醫學院醫學系臨床醫學研究所 2天主教耕莘醫院新店總院外科部一般外科乳房醫學中心 3泌尿外科 4台北醫學大學雙和醫院神經科 5暈眩及平衡障礙中心 6腎臟內科 7台北醫學大學醫學院醫學系神經學科 8中央研究院基因體研究中心 107.03.18外科年會乳房外科(國防醫學院)

Purpose As a result, identifying molecular markers to predict prognosis is thus urgently needed. The majority of patients with TNBC exhibited a poor response to chemotherapy. 70~75% triple-negative are basal gene expression, adjuvant therapy is commonly used to treat patients after surgery.

Material and methods We investigated the correlation of TNFSF13 expression with tumor growth of basal-like breast cancers and its transcriptional activity upon chemo-sensitivity of basal-like breast cancers We used RT-PCR technique to validate the gene expression of TNFSF13 in a panel of TNBC cell lines. We utilized public database to perform a global meta-analysis and prognostic estimation against TNFSF13 transcript.

A globally meta-analysis of TNFSF13 using PrognoScan database (GEO) Nucleic Acids Research, Volume 41, Issue D1, 1 January 2013, Pages D991–D995, https://doi.org/10.1093/nar/gks1193

Kaplan-Meier analysis for TNFSF13 K-M Plotter database Survexpress database http://kmplot.com/analysis/ PLoS One. 2013 Sep 16;8(9):e74250. doi: 10.1371/journal.pone.0074250. eCollection 2013

Transcriptional profiling and prognostic significance of TNFSF13 transcript in different subtypes of breast cancer (A) Heatmap of TNFSF13 mRNA levels in normal breast tissues and PAM50 subtyping breast cancer tissues. (B) Comparison of TNFSF13 transcript in normal breast tissues (NT) and luminal A (Lum A), luminal B (Lum B), HER2-enriched (HER2) and basal-like (BL) breast cancer tissues. Statistical significance was analyzed by One-way ANOVA using Turkey’s test. (C) Differential display of TNFSF13 transcript in paired normal adjacent tissues (NAT) and breast tumor tissues from patients with basal-like breast cancer (red lines) and other breast cancer subtypes (gray lines). Paired t-test was used to evaluate the statistical difference. (D) Kaplan-Meier analysis for TNFSF13 transcript using K-M Plotter database under the condition of recurrence-free survival (RFS) probability in patients with different PAM50 subtyping breast cancers. (E) Univariate analysis using Cox regression test for TNFSF13 transcript against patients with different breast cancer subtypes.

Correlation among TNFSF13 expression, tumor growth and chemosensitivity in breast cancer cell lines (A) RT-PCR analysis for TNFSF13 and GAPDH transcripts in a panel of breast cancer cell lines. The normalized TNFSF13 expression levels against GAPDH transcripts are presented in lower histogram. (B) Correlation between normalized TNFSF13 expression levels and tumor growth in the tested basal-like breast cancer cells. (C) Correlation of TNFSF13 expression levels detected RT-PCR and microarray in basal-like breast cancer cells. Spearman’s correlation test was used to analyze the statistical significance in B and C. (D) The differences of TNFSF13 mRNA level in untreated (UT) and eribulin (ERI) or paclitaxel (PTX)-treated breast cancer cells. The statistical difference was analyzed by paired t-test.

Prognostic significance of TNFSF13 transcript in adjuvant or neoadjuvant chemotherapy-treated patients with PAM50 subtyping breast cancers. Kaplan-Meier analysis was performed using K-M Plotter database under the condition of RFS probability against breast cancer patients who were classified into different PAM50 breast cancer subtypes and recorded to receive pre or post-operative chemotherapy.

Summary TNFSF13  unfavorable outcomes  poor recurrence-free survival rate Basal like breast cancer , TNFSF13  good prognosis as they received chemotherapy. TNFSF13 expression is negatively correlated with the in vivo tumor growth and dramatically downregulated after paclitaxel and eribulin treatments in TNBC cells.

mIR 17 negative correlation with TNFSF13

Poor pronosis mIR17 TNFSF13 https://genome-cancer.ucsc.edu/proj/site/hgHeatmap/

Conclusion TNFSF13 may be a useful biomarker for predicting chemotherapy response in basal-like breast cancer patients. This finding might also decline patients suffer to unnecessary chemotherapeutic treatments.

Thank you

Prognosis of the TNBC Lung mets is doubling compared with non-triple negative; brain mets is 3 times Rates of breast-specific survival in triple-negative and other breast cancers. Rates of distant recurrences following surgery in triple-negative and other breast cancers. Rebecca Dent et al. Clin Cancer Res 2007;13:4429-4434