Evaluation of MMP2 and Caspase-3 expression in 107 cases of papillary thyroid carcinoma and its association with prognostic factors

Saffar, Hiva; Sanii, Sanaz; Emami, Binesh; Heshmat, Ramin; Panah, Vahid Hagh; Azimi, Sima; Tavangar, Seyed Mohammad

doi:10.1016/j.prp.2012.06.011

Cited by 19 publications

(12 citation statements)

References 36 publications

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“…Among them, caspase-3/9 is one of the pro-apoptotic factors locating in the upstream of caspase cascade reaction. Moreover, it is also one of the most critical components in the caspase system that induces cell apoptosis (23,24). We also confirmed that overexpression of miRnA-148a significantly induced Bax protein expression and caspase-3/9 levels, and suppressed phosphorylation of STAT3 (p-STAT3), PI3K and p-Akt protein expression of papillary thyroid cancer in vitro.…”

Section: Discussionsupporting

confidence: 73%

miRNA-148a inhibits cell growth of papillary thyroid cancer through STAT3 and PI3K/AKT signaling pathways

Han

Zhu

et al. 2017

Oncology Reports

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The function of miRNA‑148a in lymphatic metastases of papillary thyroid cancer and its mechanism were tested. In this investigation, miRNA‑148a expression of lymphatic metastases of papillary thyroid cancer patients was inhibited, compared with normal group. We found that miRNA‑148a overexpression was effectively reduced cell cell proliferation and metastases, and induced apoptosis of papillary thyroid cancer in vitro. Overexpression of miRNA‑148a significantly induced Bax protein expression and caspase‑3/9 levels, and suppressed phosphorylation STAT3 (p‑STAT3), PI3K and p‑Akt protein expression of papillary thyroid cancer in vitro. Next, si‑STAT3, could inhibit p‑STAT3 protein expression, reducing cell-cell proliferation and metastases, and inducing apoptosis of papillary thyroid cancer following miRNA‑148a overexpression. Then, the PI3K inhibitor was able to inhibit PI3K and p‑Akt protein expression, reduced cell cell proliferation and metastases, and induced apoptosis of papillary thyroid cancer following miRNA‑148a overexpression. Taken together, our results suggest that miRNA‑148a inhibits lymphatic metastases of papillary thyroid cancer through STAT3 and PI3K/AKT signaling pathways.

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Section: Discussionsupporting

confidence: 73%

miRNA-148a inhibits cell growth of papillary thyroid cancer through STAT3 and PI3K/AKT signaling pathways

Han

Zhu

et al. 2017

Oncology Reports

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“…Papillary thyroid carcinoma (PTC) is the predominant histological type of thyroid malignancy, accounting for 80%‒85% of cases [ 1 , 2 ]. Previous studies always focused on female patients with PTC.…”

Section: Introductionmentioning

confidence: 99%

Serum MMP-2 as a potential predictive marker for papillary thyroid carcinoma

Shi

et al. 2018

PLoS ONE

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ObjectiveThe prevalence of papillary thyroid carcinoma (PTC) is rising rapidly. However, there are no reliable serum biomarkers for PTC. This study aimed to investigate the validity of preoperative serum matrix metalloproteinase-2 (MMP-2) as a biomarker for predicting prognosis of PTC after total or partial thyroidectomy.MethodsMale patients with PTC or a benign thyroid nodule (BTN) and healthy controls (HCs) were retrospectively included. Receiver operating characteristic (ROC) curves were constructed to evaluate the performance of preoperative serum MMP-2 in diagnosing PTC, predicting lymph node metastasis (LNM), and predicting structurally persistent/recurrent disease (SPRD). Multivariate logistic regression and Cox regression were applied to identify independent risk factors for SPRD.ResultsThe preoperative serum MMP-2 concentration in the PTC group was higher than those in BTN and HC groups. The concentration of postoperative serum MMP-2 decreased in comparison with pre-operation. ROC curves showed that serum MMP-2 could differentially diagnose PTC from BTN at the cutoff value of 86.30 ng/ml with an area under the curve (AUC) of 0.905 and could predict central LNM (CLNM) at the cutoff value of 101.55 ng/ml with an AUC of 0.711. Serum MMP-2 ≥101.55 ng/ml, age ≥45 years, and advanced TNM stage were independent risk factors for CLNM. Patients with SPRD had a higher median MMP-2 level (149.22 ng/ml) than patients without SPRD (104.55 ng/ml). Serum MMP-2 at the cutoff value of 144.04 ng/ml could predict SPRD in PTC patients with an AUC of 0.803. Advanced TNM stage and serum MMP-2 ≥144.04 ng/ml were independent risk factors for SPRD. Patients with serum MMP-2 ≥144.04 ng/ml had a worse clinical outcome than those with MMP-2 <144.04 ng/ml.ConclusionPreoperative serum MMP-2 may serve as a biomarker for diagnosing PTC and a predictive indicator for LNM and SPRD in male patients with PTC.

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“…Cleaved caspase-3 leads to proteolysis and ultimately apoptosis of cells. Few studies addressed cleaved caspase-3 in thyroid carcinomas, showing no predictive or prognostic role in thyroid carcinomas [ 41 , 42 ]. Some studies have also linked the expression of caspase-3 with aggressiveness of the tumor in PTC [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

An Appraisal of Proliferation and Apoptotic Markers in Papillary Thyroid Carcinoma: An Automated Analysis

et al. 2016

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IntroductionProliferation and apoptosis are opposing processes by which the cell numbers are kept in a delicate balance, essential for tissue homeostasis, whereas uncontrolled growth of cells is a hallmark of cancer. Papillary thyroid cancer (PTC) is the commonest type of thyroid cancer, with some PTC following an indolent course, whereas the other ones are more aggressive.AimTo evaluate respective contribution of proliferation and apoptosis in the tumorigenesis of PTC by automated analysis.Materials and MethodsWe investigated the immunolabeling of phosphorylated histone H3 (pHH3), cyclin D1, active caspase-3, and bcl-2 in thirteen cases each of metastatic PTC, follicular variant of PTC (FVPTC), papillary microcarcinoma (PMC) and well differentiated tumor of uncertain malignant potential (WDT-UMP). FVPTC cases comprised seven encapsulated and six unencapsulated cases.ResultsProliferation, as assessed by pHH3 and cyclin D1 immunolabeling, was increased in all PTC variants, including the putative precursor lesion WDT-UMP, compared to normal thyroid tissue. pHH3 was immunolabeled in more cells of metastatic PTC than of PMC and of encapsulated FVPTC. Surprisingly, metastatic PTC and unencapsulated FVPTC also demonstrated more cleaved caspase-3 immunolabeled cells than the other types. In contrast, increased expression of bcl-2 protein was seen in normal thyroid areas, encapsulated FVPTC and PMC as compared to metastatic PTC. Metastatic PTC shows higher proliferation than other types of PTC but unexpectedly also higher apoptotic levels. Similar results were also seen with unencapsulated FVPTC, thus suggesting that unencapsulated FVPTC has a potential for adverse outcome. Bcl-2 was immunolabeled in a low percentage of cells in WDT-UMP.ConclusionsThe expression of the proliferative protein pHH3 together with the apoptotic marker cleaved caspase-3 may indicate an aggressive behaviour of PTC and loss of apoptosis inhibition by bcl-2 protein can further amplify the role of these proteins in tumor progression. Both cyclin D1 and bcl-2 could prove to be interesting markers of PTC precursor lesions. Automated/digital image quantification approach helps in refining the diagnostic accuracy.

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Evaluation of MMP2 and Caspase-3 expression in 107 cases of papillary thyroid carcinoma and its association with prognostic factors

Cited by 19 publications

References 36 publications

miRNA-148a inhibits cell growth of papillary thyroid cancer through STAT3 and PI3K/AKT signaling pathways

miRNA-148a inhibits cell growth of papillary thyroid cancer through STAT3 and PI3K/AKT signaling pathways

Serum MMP-2 as a potential predictive marker for papillary thyroid carcinoma

An Appraisal of Proliferation and Apoptotic Markers in Papillary Thyroid Carcinoma: An Automated Analysis

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