Figure 1.
Differentially expressed genes between tumors in TCGA datasets with high and low expression of TTP.
Gene expression profiling showing differentially expressed genes between TTP-high and TTP-low expressing tumors in TCGA breast cancer (A), lung adenocarcinoma (B), lung squamous cell carcinoma (C), and colon adenocarcinoma (D) databases. Information regarding the tumor samples in the TTP-high and TTP-low cohorts and the differentially expressed genes for each tumor type is presented in S1, S2, S3, S4, S5, S6, S7, S8 Tables. All genes shown are hierarchically clustered, have >2.0-fold change, and are significantly altered by unpaired t-test analysis (corrected p-value <0.05).
Figure 2.
Identification of the TTP-low tumor gene signature.
Venn diagram showing the overlap of differentially expressed genes between TTP-high and TTP-low expressing tumors. The center of the diagram indicates that there are 50 genes shared by all four cancer datasets that make up the TTP-low tumor gene signature. These 50 genes are listed in Table 1, and their fold change in each tumor dataset is listed in Table 2.
Table 1.
AREs located in genes in the TTP-low tumor gene signature.
Table 2.
Fold change in gene expression between high and low TTP-expressing tumors in TCGA datasets.
Figure 3.
Low expression of TTP connotes poor outcome for breast cancer and lung adenocarcinoma patients.
Relapse-free survival data from TCGA breast cancer (A) and overall survival data from TCGA lung adenocarcinoma (B), lung squamous cell carcinoma (C), and colon adenocarcinoma (D) was used to generate Kaplan-Meier survival curves of TTP-high versus TTP-low patients in each dataset. The p-values were determined by the Mantel-Cox log-rank test.
Table 3.
Top 20 other human cancers with similarities to the TTP-low tumor gene signature.
Figure 4.
Differences in breast cancer biomarkers and lung adenocarcinoma mutations based on TTP expression levels.
(A) Percentages of estrogen receptor-negative (ER-), progesterone receptor-negative (PR-), human epidermal growth factor receptor 2-enriched-positive (HER2+), and triple negative breast cancer (TNBC) patients in the TTP-high and TTP-low TCGA breast cancer sets. (B) Percentages of ERBB4, KRAS, and STK11 mutations in TTP-high and TTP-low TCGA lung adenocarcinoma patients.
Figure 5.
Low TTP expression correlates with more aggressive tumor subtypes and advanced tumor stage.
Percentages of tumor expression subtypes (left column) and tumor stage (right column) are shown for patients in the TTP-high and TTP-low groups for TCGA breast cancer (A and B), lung adenocarcinoma (C and D), lung squamous cell carcinoma (E and F), and colon adenocarcinoma (G and H) datasets.
Table 4.
Top 20 canonical pathways significantly altered by the TTP-low tumor gene signature.
Figure 6.
Low TTP levels correlate with increased tumor necrosis in breast cancer and lung adenocarcinoma.
Average percentages of tumor necrosis in TTP-high and TTP-low tumors in TCGA breast cancer, lung adenocarcinoma, lung squamous cell carcinoma, and colon adenocarcinoma datasets. The p-values were determined by Student's t-test (*p<0.05, *** p<0.001).
Figure 7.
CREB-target genes are a core component of the TTP-low tumor gene signature.
Diagram of the 20 CREB-target genes found by Ingenuity Pathway Analysis in the TTP-low tumor gene signature.
Figure 8.
Expression of CREB family members in breast cancer and lung adenocarcinoma based on TTP levels.
Gene expression profiling showing the expression levels of canonical CREB family members (A), and comparing the expression levels of CREM versus its dominant negative splice variants ICER and CREMΔZIP (C) in TTP-high and TTP-low expressing TCGA breast cancers and lung adenocarcinomas. (B) Cartoon showing the canonical CREM protein and its dominant negative splice variants ICER and CREMΔZIP.
Table 5.
Top 10 upstream regulators of the TTP-low tumor gene signature.