Role of CXCR4 and MMP-9 Expressions with Regional Cervical Lymph Nodes Metastatic Status in Papillary Thyroid Carcinoma

Kusumastuti, Etty Hary; Djafar, Nurdhani Hi; Rahniayu, Alphania

doi:10.33371/ijoc.v15i2.771

Cited by 2 publications

(1 citation statement)

References 25 publications

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“…Several studies have examined the associations between MMP9 expression levels and clinicopathological parameters reflective of TC progression and prognosis (Table 6) [23,[61][62][63][64]73,77,78]. Higher MMP9 expression has been consistently associated with the presence of lymph node metastasis compared to PTC without metastasis in multiple studies [21,22,62,65,67,79,80].…”

Section: Associations With Clinicopathological Featuresmentioning

confidence: 99%

Matrix Metalloproteinase 9/microRNA-145 Ratio: Bridging Genomic and Immunological Variabilities in Thyroid Cancer

Toraih,

Hussein,

Al Ageeli

et al. 2023

Biomedicines

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Matrix metalloproteinase 9 (MMP9) and microRNA-145 (miR-145) have emerged as essential biomarkers in thyroid cancer progression and metastasis. However, their combined evaluation and clinical utility as a unified prognostic marker across diverse thyroid cancer subgroups remain unexplored. We investigated the diagnostic and prognostic value of the MMP9/miR-145 ratio in thyroid cancer, hypothesizing it may overcome inter-patient heterogeneity and serve as a versatile biomarker regardless of genetic mutations or autoimmune status. MMP9 and miR-145 expressions were analyzed in 175 paired papillary thyroid cancer (PTC) and normal tissues. Plasma levels were assessed perioperatively and longitudinally over 12–18 months in 86 matched PTC patients. The associations with clinicopathological parameters and patient outcomes were evaluated. MMP9 was upregulated, and miR-145 downregulated in cancer tissues, with a median MMP9/miR-145 ratio 17.6-fold higher versus controls. The tissue ratio accurately diagnosed thyroid malignancy regardless of BRAF mutation or Hashimoto’s thyroiditis status, overcoming genetic and autoimmune heterogeneity. A high preoperative circulating ratio predicted aggressive disease features, including lymph node metastasis, extrathyroidal extension, progression/relapse, and recurrence. Although the preoperative plasma ratio was elevated in patients with unfavorable outcomes, it had limited utility for post-surgical monitoring. In conclusion, the MMP9/miR-145 ratio is a promising biomarker in PTC that bridges genetic and immunological variabilities, enhancing preoperative diagnosis and prognostication across diverse patient subgroups. It accurately stratifies heterogenous cases by aggressiveness. The longitudinal trends indicate decreasing applicability for post-thyroidectomy surveillance. Further large-scale validation and protocol standardization can facilitate clinical translation of the MMP9/miR-145 ratio to guide personalized thyroid cancer management.

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Section: Associations With Clinicopathological Featuresmentioning

confidence: 99%

Matrix Metalloproteinase 9/microRNA-145 Ratio: Bridging Genomic and Immunological Variabilities in Thyroid Cancer

Toraih,

Hussein,

Al Ageeli

et al. 2023

Biomedicines

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Comparative evaluation of somatostatin and CXCR4 receptor expression in different types of thyroid carcinoma using well-characterised monoclonal antibodies

et al. 2022

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Background Papillary and follicular thyroid carcinomas can be treated surgically and with radioiodine therapy, whereas therapeutic options for advanced stage IV medullary and for anaplastic tumours are limited. Recently, somatostatin receptors (SSTs) and the chemokine receptor CXCR4 have been evaluated for the treatment of thyroid carcinomas, however, with contradictory results. Methods The expression of the five SSTs and of CXCR4 was assessed in 90 samples from 56 patients with follicular, papillary, medullary, or anaplastic thyroid carcinoma by means of immunohistochemistry using well-characterised monoclonal antibodies. The stainings were evaluated using the Immunoreactivity Score (IRS) and correlated to clinical data. In order to further substantiate the immunohistochemistry results, in serial sections of a subset of the samples receptor expression was additionally examined at the mRNA level using qRT-PCR. Results Overall, SST and CXCR4 protein expression was low in all four entities. In single cases, however, very high IRS values for SST2 and CXCR4 were observed. SST2 was the most frequently expressed receptor, found in 38% of cases, followed by SST5 and SST4, found in 14 and 9% of tumours, respectively. SST1 and SST3 could not be detected to any significant extent. CXCR4 was present in 12.5% of medullary and 25% of anaplastic carcinomas. Expression SST3, SST4, SST5 and CXCR4 was positively correlated with expression of the proliferation marker Ki-67. Additionally, a negative interrelationship between SST4 or SST5 expression and patient survival and a positive association between SST3 expression and tumour diameter were observed. qRT-PCR revealed a similar receptor expression pattern to that seen at the protein level. However, probably due to the low overall expression, no correlation was found for the SSTs or the CXCR4 between the IRS and the mRNA values. Conclusions SST- or CXCR4-based diagnostics or therapy in thyroid carcinomas should not be considered in general but may be feasible in single cases with high levels of expression of these receptors.

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Role of CXCR4 and MMP-9 Expressions with Regional Cervical Lymph Nodes Metastatic Status in Papillary Thyroid Carcinoma

Cited by 2 publications

References 25 publications

Matrix Metalloproteinase 9/microRNA-145 Ratio: Bridging Genomic and Immunological Variabilities in Thyroid Cancer

Matrix Metalloproteinase 9/microRNA-145 Ratio: Bridging Genomic and Immunological Variabilities in Thyroid Cancer

Comparative evaluation of somatostatin and CXCR4 receptor expression in different types of thyroid carcinoma using well-characterised monoclonal antibodies

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