Dataset Information

Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer.

ABSTRACT: The Krüppel-like factor 5 (KLF5), a zinc-finger transcriptional factor, is highly expressed in several solid tumors, but its role in PTC remains unclear. We investigated the expression of KLF5 protein in a large cohort of PTC patient samples and explored its functional role and mechanism in PTC cell lines in vitro and in vivo. KLF5 overexpression was observed in 65.1% of all PTC cases and it was significantly associated with aggressive clinico-pathological parameters and poor outcome. Given the significant association between KLF5 and HIF-1? overexpression in PTC patients, we investigated the functional correlation between KLF5 and HIF-1? in PTC cells. Indeed, the analysis revealed the co-immunoprecipitation of KLF5 with HIF-1? in PTC cells. We also identified KLF5-binding sites in the HIF-1? promoter that specifically bound to KLF5 protein. Mechanistically, KLF5 promoted PTC cell growth, invasion, migration, and angiogenesis, while KLF5 downregulation via specific inhibitor or siRNA reverses its action in vitro. Importantly, the silencing of KLF5 decreases the self-renewal ability of spheroids generated from PTC cells. In addition, the depletion of KLF5 reduces PTC xenograft growth in vivo. These findings suggest KLF5 can be a possible new molecular therapeutic target for a subset of PTC.

SUBMITTER: Pratheeshkumar P

PROVIDER: S-EPMC7825749 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer.

Pratheeshkumar Poyil P Siraj Abdul K AK Divya Sasidharan Padmaja SP Parvathareddy Sandeep Kumar SK Siraj Sarah S Diaz Roxanne R Begum Rafia R Al-Sobhi Saif S SS Al-Dayel Fouad F Al-Kuraya Khawla S KS

Cancers 20210107 2

The Krüppel-like factor 5 (KLF5), a zinc-finger transcriptional factor, is highly expressed in several solid tumors, but its role in PTC remains unclear. We investigated the expression of KLF5 protein in a large cohort of PTC patient samples and explored its functional role and mechanism in PTC cell lines in vitro and in vivo. KLF5 overexpression was observed in 65.1% of all PTC cases and it was significantly associated with aggressive clinico-pathological parameters and poor outcome. Given the ...[more]

PMID: 33430300

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Project description:IntroductionThyroid cancer is a very common malignant tumor in the endocrine system, while the incidence of papillary thyroid carcinoma (PTC) throughout the world also shows a trend of increase year by year. In this study, we constructed two models: ICIscore and Riskscore. Combined with these two models, we can make more accurate and reasonable inferences about the prognosis of PTC patients.MethodsWe selected 481 PTC samples from TCGA and 147 PTC samples from GEO (49 samples in GSE33630, 65 samples in GSE35570 and 33 samples in GSE60542). We performed consistent clustering for them and divided them into three subgroups and screened differentially expressed genes from these three subgroups. Then we divided the differential genes into three subtypes. We also distinguished the up-regulated and down-regulated genes and calculated ICIscore for each PTC sample. ICIscore consists of two parts: (1) the PCAu was calculated from up-regulated genes. (2) the PCAd was calculated from down-regulated genes. The PCAu and PCAd of each sample were the first principal component of the relevant gene. What's more, we divided the patients into two groups and constructed mRNA prognostic signatures. Additionally we also verified the independent prognostic value of the signature.ResultsThough ICIscore, we were able to observe the relationship between immune infiltration and prognosis. The result suggests that the activation of the immune system may have both positive and negative consequences. Though Riskscore, we could make more accurate predictions about the prognosis of patients with PTC. Meanwhile, we also generated and validated the ICIscore group and Riskscore group respectively.ConclusionAll the research results show that by combining the two models constructed, ICIscore and Riskscore, we can make a more accurate and reasonable inference about the prognosis of patients with clinical PTC patients. This suggests that we can provide more effective and reasonable treatment plan for clinical PTC patients.

Dataset Information

Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer.

Publications

Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer.

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