TGFβ isoforms and receptors mRNA expression in breast tumours: prognostic value and clinical implications

Abstract

BackgroundTransforming growth factor beta (TGFβ) signalling is involved in both tumour suppression and tumour progression. The mRNA expression levels of the TGFβ isoforms and receptors in breast tumours may have prognostic value and clinical implications.MethodsThe mRNA levels of TGFB1, TGFB2, TGFB3, TGFBR1 and TGFBR2 were analysed in primary breast tumours and adjacent normal breast tissues, and the associations with tumour characteristics and patients’ overall and relapse-free survival were evaluated, using the public gene expression microarray data from The Cancer Genome Atlas (n = 520) and the Gene Expression Omnibus (four datasets) and our quantitative real-time PCR validation data (n = 71).ResultsSignificantly higher TGFB1 and TGFB3 mRNA levels and lower TGFBR2 mRNA levels were observed in primary tumours compared with their paired normal tissues. TGFB1 mRNA expression was seemly lower in triple-negative tumours and in tumours from lymph node-negative patients. TGFB3 mRNA expression was significantly lower in estrogen receptor-negative/progesterone receptor-negative/Basal-like/Grade 3 tumours. High TGFB2, TGFB3 and TGFBR2 mRNA levels in tumours were generally associated with better prognosis for patients, especially those diagnosed with lymph node-negative diseases. High TGFBR1 mRNA levels in tumours were associated with poorer clinical outcomes for patients diagnosed with small (diameter ≤2 cm) tumours.ConclusionsThe results indicate a reduced responsiveness of tumour cells to TGFβ, a preferential up-regulation of TGFB1 in malignant tumours and a preferential up-regulation of TGFB3 in premalignant tumours. The results may not only provide prognostic value for patients but also assist in classifying tumours according to their potential responses to TGFβ and selecting patients for TGFβ signalling pathway targeted therapies.

Methylation silencing of TGF-β receptor type II is involved in malignant transformation of esophageal squamous cell carcinoma

“…These results have indicated that loss of TGFBR2 expression promotes epithelial oncogenesis. Several studies have shown that TGFBR2 inhibits cell growth, invasion, migration, and metastasis in breast and pancreatic cancer [30,31]. TCGA consortium and others have reported the mutations of TGFBR2 in ESCC [26].…”

Microarray and RNA in situ hybridization assay for recurrence risk markers of breast carcinoma and ductal carcinoma in situ: Evidence supporting the use of diverse pathways panels

“…Seventeen markers were found to be differentially expressed: 7 lncRNAs, AC078802.1 to 2, BBC3-1, CHURC1-FNTB-1, FER3, RAD21-AS1-1, SLC39A8-1, and ZEB1-2 (Table 3A), none of which have current citations in PubMed; and, 10 mRNAs, upregulated: GLO1, GLTSCR2, TGFB1, RAB34; downregulated: IL2RA, INTS6, MXD1, RAB5B, TCF20 (SPBP), TLR2 (Table 3B); associations with breast or other cancers have previously been reported for all 10. [12][13][14][15][16][17][18][19][20][21] Of the upregulated mRNAs, TGFB1 and RAB34 are commonly cited as associated with proliferation and of the downregulated group INTS6 is cited as a tumor suppressor gene (search and review of the NCBI gene database https://www.ncbi. nlm.nih.gov/gene).…”

Long non‐coding NR2F1‐AS1 is associated with tumor recurrence in estrogen receptor‐positive breast cancers

“…Since late metastasis has been confined to the reactivation of dormant DTCs, these results highlighted the coexistence of cell subpopulations at different points of the dormant-toawaken state. To resume proliferation, quiescent cells activate EGF, RAS, TGFb1, and TGFb3, which upregulation have been attributed to cause higher malignancy in breast tumors (Chen et al, 2015;Lo et al, 2006). To investigate the metastatic potential of NR2F1-AS1, we firstly tested whether NR2F1-AS1 influences anoikis resistance in BT474 cells.…”