PROX1 Promotes Secretory Granule Formation in Medullary Thyroid Cancer Cells

Ishii, Jun; Yazawa, Takuya; Chiba, Tomohiro; Shishido‐Hara, Yukiko; Arimasu, Yuu; Sato, Hidemitsu; Kamma, Hiroshi

doi:10.1210/en.2015-1973

Cited by 12 publications

(15 citation statements)

References 34 publications

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“… 9 Among these three signatures, only one gene, SCG2 , overlapped between the gene-pair signature and 13-gene signature, which has been reported in multiple cancers. 19 – 21 This may have contributed to the limited sample size and subsequent selection bias, and a systematic method was needed to identify the prognostic genes. In addition, no signatures based on the microarray data were validated in the RNA-sequencing data, and this may affect their further application in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

A novel gene-pair signature for relapse-free survival prediction in colon cancer

Chen

Wang

Zhang

et al. 2018

CMAR

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BackgroundColon cancer (CC) patients with early relapse usually have a poor prognosis. In this study, we aimed to identify a novel signature to improve the prediction of relapse-free survival (RFS) in CC.MethodsFour microarray datasets were merged into a training set (n=1,045), and one RNA-sequencing dataset was used as a validation set (n=384). In the training set, microarray meta-analysis screened out 596 common RFS-related genes across datasets, which were used to construct 177,310 gene pairs. Then, the LASSO penalized generalized linear model identified 16 RFS-related gene pairs, and a risk score was calculated for each sample according to the model coefficients.ResultsThe risk score demonstrated a good ability in predicting RFS (area under the curve [AUC] at 5 years: 0.724; concordance index [C-index]: 0.642, 95% CI: 0.615–0.669). High-risk patients showed a poorer prognosis than low-risk patients (HR: 3.519, 95% CI: 2.870–4.314). Subgroup analysis reached consistent results when considering multiple confounders. In the validation set, the risk score had a similar performance (AUC at 5 years: 0.697; C-index: 0.696, 95% CI: 0.627–0.766; HR: 2.926, 95% CI: 1.892–4.527). When compared with a 13-gene signature, a 15-gene signature, and TNM stage, the score showed a better performance (P<0.0001; P=0.0004; P=0.0125), especially for the patients with a longer follow-up (R2=0.988, P<0.0001). When the follow-up was >5 years (n=314), the score demonstrated an excellent performance (C-index: 0.869, 95% CI: 0.816–0.922; HR: 13.55, 95% CI: 7.409–24.78).ConclusionOur study identified a novel gene-pair signature for prediction of RFS in CC.

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Section: Discussionmentioning

confidence: 99%

A novel gene-pair signature for relapse-free survival prediction in colon cancer

Chen

Wang

Zhang

et al. 2018

CMAR

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“…Analysis of the RNA-seq has identified both CSMs as well as potential regulators of thyroid fate in AFE and early TPs. Some of the TFs identified ( Irx5 , Hoxb8 , Isl1 ) have been involved in mouse foregut and thyroid development ( Millien et al., 2008 , Westerlund et al., 2008 ), while others, such as PROX1 , have been implicated in human thyroid disease ( Ishii et al., 2016 ). Future PSC-based and in vivo studies will unravel the thyroid-related function of select TFs during thyroid specification and development.…”

Section: Discussionmentioning

confidence: 99%

Thyroid Progenitors Are Robustly Derived from Embryonic Stem Cells through Transient, Developmental Stage-Specific Overexpression of Nkx2-1

et al. 2017

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SummaryThe clinical importance of anterior foregut endoderm (AFE) derivatives, such as thyrocytes, has led to intense research efforts for their derivation through directed differentiation of pluripotent stem cells (PSCs). Here, we identify transient overexpression of the transcription factor (TF) NKX2-1 as a powerful inductive signal for the robust derivation of thyrocyte-like cells from mouse PSC-derived AFE. This effect is highly developmental stage specific and dependent on FOXA2 expression levels and precise modulation of BMP and FGF signaling. The majority of the resulting cells express thyroid TFs (Nkx2-1, Pax8, Foxe1, Hhex) and thyroid hormone synthesis-related genes (Tg, Tpo, Nis, Iyd) at levels similar to adult mouse thyroid and give rise to functional follicle-like epithelial structures in Matrigel culture. Our findings demonstrate that NKX2-1 overexpression converts AFE to thyroid epithelium in a developmental time-sensitive manner and suggest a general methodology for manipulation of cell-fate decisions of developmental intermediates.

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“…Generally, anti-PDGFβ drugs play an auxiliary role in anti-VEGF treatment. Some other markers, such as CRISP-3 94, CCR7 168, GATA2 169, Prox1 170, and Foxc2 171 have also been found and are well used in the treatment. In conclusion, abnormal tumor vasculature exhibited remarkable spatiotemporal heterogeneousness, and not only damaged perfusion and drug delivery, but also made chemoradiotherapy less expeditious.…”

Section: The Blood and Lymphatic Vascular Networkmentioning

confidence: 99%

Role of tumor microenvironment in tumorigenesis

et al. 2017

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Tumorigenesis is a complex and dynamic process, consisting of three stages: initiation, progression, and metastasis. Tumors are encircled by extracellular matrix (ECM) and stromal cells, and the physiological state of the tumor microenvironment (TME) is closely connected to every step of tumorigenesis. Evidence suggests that the vital components of the TME are fibroblasts and myofibroblasts, neuroendocrine cells, adipose cells, immune and inflammatory cells, the blood and lymphatic vascular networks, and ECM. This manuscript, based on the current studies of the TME, offers a more comprehensive overview of the primary functions of each component of the TME in cancer initiation, progression, and invasion. The manuscript also includes primary therapeutic targeting markers for each player, which may be helpful in treating tumors.

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PROX1 Promotes Secretory Granule Formation in Medullary Thyroid Cancer Cells

Cited by 12 publications

References 34 publications

A novel gene-pair signature for relapse-free survival prediction in colon cancer

A novel gene-pair signature for relapse-free survival prediction in colon cancer

Thyroid Progenitors Are Robustly Derived from Embryonic Stem Cells through Transient, Developmental Stage-Specific Overexpression of Nkx2-1

Role of tumor microenvironment in tumorigenesis

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