Prognostic significance of TBX2 expression in non-small cell lung cancer

Hu, Bo; Mu, Hai-Ping; Zhang, Yuqing; Su, Chong-Yi; Song, Jiantao; Meng, Chong; Liu, Dong-Xing

doi:10.1007/s10735-014-9569-0

Cited by 12 publications

(11 citation statements)

References 14 publications

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“…Up-regulation of TBX2 has been reported in a wide range types of cancer [ 13 – 19 ]. In the present study, we reported that TBX2 mRNA and protein expression was significantly higher in NPC tissues samples than that in the adjacent normal tissues.…”

Section: Discussionmentioning

confidence: 99%

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TBX2 over-expression promotes nasopharyngeal cancer cell proliferation and invasion

Chen

et al. 2017

Oncotarget

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TBX2 is a member of the T box transcription factor family. Its expression and potential biological functions in nasopharyngeal cancer (NPC) cells are studied here. We showed that TBX2 mRNA and protein expression was significantly elevated in multiple human NPC tissues, as compared with that in adjacent normal tissues. Knockdown of TBX2 by targeted-siRNA significantly inhibited proliferation and invasion of NPC cells (CNE-1 and HONE-1 lines). Meanwhile, TBX2 knockdown also induced G1-phase cell cycle arrest. At the molecular level, we discovered that expressions of several tumor suppressor genes, including p21, p27, phosphatase with tensin homology (PTEN) and E-Cadherin, were increased dramatically after TBX2 knockdown in above NPC cells. Collectively, our results imply that TBX2 over-expression promotes NPC cell proliferation and invasion, possibly via silencing several key tumor suppressor genes.

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Section: Discussionmentioning

confidence: 99%

“…Existing evidences have linked TBX2 to tumorigenesis. TBX2 expression is up-regulated in a wide range of cancers, including melanoma [ 13 ], pancreatic cancer [ 14 ], bladder cancer, breast cancer [ 15 – 17 ], colorectal cancer [ 18 ] and lung cancer [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

TBX2 over-expression promotes nasopharyngeal cancer cell proliferation and invasion

Chen

et al. 2017

Oncotarget

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“…We found that most of those probes identified in 7 cancers are located in non-island regions. Moreover, some genes of those CpG sites located have been reported to be associated with the prognosis of various cancers (such as SHANK2 [31], LTBP1 [32], GRIA4 [33], OSR2 [33], PHLDB2 [34], TBX2 [35][36][37] and GPR37 [38]). Currently, no qualified independent dataset is available for systematically estimating the reproducibility and validity of the probe-based prognostic classifier, thus a further verification of this prognostic model would be necessary in the future.…”

Section: Prognostic Model Successfully Divides Patients Into High-rismentioning

confidence: 99%

Integrative analysis identifies potential DNA methylation biomarkers for pan-cancer diagnosis and prognosis

2019

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DNA methylation status is closely associated with diverse diseases, and is generally more stable than gene expression, thus abnormal DNA methylation could be important biomarkers for tumor diagnosis, treatment and prognosis. However, the signatures regarding DNA methylation changes for pan-cancer diagnosis and prognosis are less explored. Here we systematically analyzed the genome-wide DNA methylation patterns in diverse TCGA cancers with machine learning. We identified seven CpG sites that could effectively discriminate tumor samples from adjacent normal tissue samples for 12 main cancers of TCGA (1216 samples, AUC > 0.99). Those seven potential diagnostic biomarkers were further validated in the other 9 different TCGA cancers and 4 independent datasets (AUC > 0.92). Three out of the seven CpG sites were correlated with cell division, DNA replication and cell cycle. We also identified 12 CpG sites that can effectively distinguish 26 different cancers (7605 samples), and the result was repeatable in independent datasets as well as two disparate tumors with metastases (micro-average AUC > 0.89). Furthermore, a series of potential signatures that could significantly predict the prognosis of tumor patients for 7 different cancer were identified via survival analysis (p-value < 1e-4). Collectively, DNA methylation patterns vary greatly between tumor and adjacent normal tissues, as well as among different types of cancers. Our identified signatures may aid the decision of clinical diagnosis and prognosis for pan-cancer and the potential cancer-specific biomarkers could be used to predict the primary site of metastatic breast and prostate cancers.

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“…Earlier reports have suggested that expression levels of TBX2 are elevated in NSCLC [ 39 , 40 ]. The reports by Hu et al [ 39 ] and Zhang et al [ 40 ] interrogated TBX2 protein by immunohistochemistry in NSCLCs alone (tissue microarrays) and suggested that tumors with relatively high expression of the protein (based on percent positivity within the tumors themselves) exhibited comparatively poor prognosis [ 39 , 40 ]. The same reports studied expression levels of the TBX2 gene (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…The same reports studied expression levels of the TBX2 gene (e.g. by quantitative real-time PCR) in NSCLCs and paired normal lung tissues in a smaller subset of NSCLC cases ( n = 40 to 50) [ 39 , 40 ] demonstrating that the gene is elevated in the tumors. These earlier studies [ 39 – 41 ], albeit few, point to putative oncogenic roles and properties for the TBX2 gene in human NSCLC.…”

Section: Discussionmentioning

confidence: 99%

TBX2subfamily suppression in lung cancer pathogenesis: a high-potential marker for early detection

et al. 2017

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The TBX2 subfamily (TBXs 2, 3, 4 and 5) transactivates or represses genes involved in lung organogenesis. Yet TBX2 subfamily expression in pathogenesis of non-small cell lung cancer (NSCLC), the most common lung malignancy, remains elusive. We sought to probe the expression profile of the TBX2 subfamily in early phases of NSCLC. Expression of TBX2 subfamily was analyzed in datasets of pan-normal specimens as well as NSCLCs and normal lung tissues. TBX2 subfamily expression in matched normal lungs, premalignant hyperplasias and NSCLCs was profiled by transcriptome sequencing. TBX2 subfamily expression was evaluated in the cancerization field consisting of matched NSCLCs and adjacent cytologically-normal airways relative to distant normal lungs and in a dataset of normal bronchial samples from smokers with indeterminate nodules suspicious for malignancy. Statistical analysis was performed using R. TBX2 subfamily expression was markedly elevated in normal lungs relative to other organ-specific normal tissues. Expression of the TBXs was significantly suppressed in NSCLCs relative to normal lungs (P < 10−9). TBX2 subfamily was significantly progressively decreased across premalignant lesions and NSCLCs relative to normal lungs (P < 10−4). The subfamily was significantly suppressed in NSCLCs and adjacent normal-appearing airways relative to distant normal lung tissues (P < 10−15). Further, suppressed TBX2 subfamily expression in normal bronchi was associated with lung cancer status (P < 10−5) in smokers. Our findings suggest that the TBX2 subfamily is notably suppressed in human NSCLC pathogenesis and may serve as a high-potential biomarker for early lung cancer detection in high-risk smokers.

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Prognostic significance of TBX2 expression in non-small cell lung cancer

Cited by 12 publications

References 14 publications

TBX2 over-expression promotes nasopharyngeal cancer cell proliferation and invasion

TBX2 over-expression promotes nasopharyngeal cancer cell proliferation and invasion

Integrative analysis identifies potential DNA methylation biomarkers for pan-cancer diagnosis and prognosis

TBX2subfamily suppression in lung cancer pathogenesis: a high-potential marker for early detection

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