Identification of MMP1 and MMP2 by RNA-seq analysis in laryngeal squamous cell carcinoma

Cao

et al. 2021

neo

This study aims to elucidate the potential genes of the matrix metalloproteinase (MMP) family, responsible for the progression of laryngeal squamous cell carcinoma (LSCC). Besides, we ascertained the changes in common malignant behaviors in vitro by knocking down MMP1. TCGA, GEO, Oncomine, and Microarray data were conducted to analyze the expression levels of MMPs and to find tissue-specific genes in LSCC. Univariate and multivariate Cox regression analyses were established in the construction of a prognostic model based on expression profiles and clinical information of LSCC in TCGA. We then comprehensively analyzed survival, co-expression network, and immune infiltration based on a prognostic model by Kaplan-Meier analysis, WGCNA, and CIBERSORT. Thereafter, qRT-PCR, proliferation, Transwell, and wound healing assays were used to assess the accuracy of the bioinformatics data. A total of seven genes in the MMP family were identified as differentially expressed genes (DEGs) by integrating three public databases and microarray data. Additionally, multivariate Cox regression was used to establish a four-gene (MMP1/3/8/10) prognostic model, which exhibited a better predictive accuracy than the TNM (tumors/nodes/metastases) based model. The prognostic model was related to plasma cells, CD8+ T cells, follicular helper T cells, resting NK cells, and M0 macrophages infiltration. The expression of MMP1, MMP3, and MMP10 was the highest in head and neck squamous cell carcinoma (HNSC) compared to other cancer in the Oncomine and GEPIA dataset. Further, MMP1 demonstrated significant upregulation in 40 paired LSCC tissues. Eventually, MMP1 downregulation inhibited cell viability, colony formation, and cell migration in TU686 and FaDu cells. Our findings suggest that the four-gene signature might be associated with the prognos is. Further, we revealed that MMP1 is a pivotal biomarker for the biotherapy and prognostic evaluation of patients with LSCC.

Section: Discussionmentioning

confidence: 98%

The matrix metalloproteinase gene family: a significant prognostic gene lineage correlated with immune infiltrates in laryngeal squamous cell carcinoma

Cao

et al. 2021

neo

“…[20] Fang and Shen (2020) have also worked on the MMP-2 by RNA sequence analysis in laryngeal cancer patients and found the upregulated expression of the protein in laryngeal cancer patients compared to controls. [21] Till now a limited number of studies have been published concerning MMP expression and the risk of LC. Most of the already reported studies have used a small study cohort of laryngeal cancer patients.…”

Section: Introductionmentioning

confidence: 99%

“…Grzelczyk et al, used 96 laryngeal cancer sections, Matulka et al, used 27 laryngeal cancer sections and, Fang and Shen (2020) used 6 sections of laryngeal cancer patients. [19][20][21] The present study is designed to check the involvement of MMP-2 and MMP-9 in a larger study cohort of laryngeal cancer patients. MMP-2 and MMP-9 expression levels were also correlated with the smoking status of laryngeal cancer patients which is considered as one of the important risk factors for laryngeal carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

Deregulation of MMP-2 and MMP-9 in laryngeal cancer: A retrospective observational study

Lin,

Ashraf,

Mahjabeen

2024

Medicine

Laryngeal carcinoma (LC) is reported to have a higher incidence rate among all types of head and neck cancers around the globe. Mechanisms resulting in the pathogenesis of LC are complicated due to involvement of invasion and metastasis and there is a need to understand this complicated multistep process. Numerous molecules including matrix metalloproteinases (MMPs) are involved in regulating metastatic mechanisms. Furthermore, activation and expression of different classes of MMPs have been observed in multiple pathological and physiological events including inflammation, invasion, and metastasis. Among all members of MMPs, matrix metalloproteinases-2 (MMP-2), and matrix metalloproteinases-9 (MMP-9) have been frequently reported to correlate with tumor pathogenesis. The present study is designed to check the involvement of MMP-2 and MMP-9 in LC pathogenesis. 184 laryngeal tumor samples along with adjacent uninvolved healthy sections were collected to check the expression deregulation of the above-mentioned gene in LC using real-time PCR and immunohistochemistry (IHC). Real-time PCR and IHC analyses showed the significant upregulation of MMP-2 (P < .0001) and MMP-9 (P < .0001) genes in laryngeal tumors compared to controls. Spearman correlation showed the positive correlation of expression deregulation of selected MMPs with advanced TNM stage [MMP-2, (P < .0001); MMP-9, P < .0001] and smoking status [MMP-2 (P < .0001); MMP-9 P < .0001] in laryngeal pathogenesis. Receiver operating curve (ROC) analysis showed the good diagnostic/prognostic value of said markers in laryngeal cancer patients. The present study showed that significant upregulation of selected MMPs was found associated with an increased risk of laryngeal cancer and can act as good diagnostic markers for the detection of said disease.

“…These data encourage to conduct of further research on potential blood- or tissue-based biomarkers for early LSCC diagnosis. Intensive and long-lasting smoking and alcohol consumption as a potentialyzer for cancerogenic smoking are the potential risk factors for the development of LSCC and are also influenced by some genetic factors [ 12 , 13 , 14 ]. The genetic factor that could potentially be important in the LSCC development is the ApoE gene.…”

Section: Introductionmentioning

confidence: 99%

The Role of ApoE Serum Levels and ApoE Gene Polymorphisms in Patients with Laryngeal Squamous Cell Carcinoma

et al. 2022

Recent studies have revealed that the inflammatory ApoE effect may play a significant role in various cancer development. However, this effect has still not been analyzed in patients with laryngeal squamous cell carcinoma (LSCC). In the present study, we evaluated two single nucleotide polymorphisms (SNPs) of ApoE (rs7412 and rs429358) and determined their associations with LSCC development and the LSCC patients’ five-year survival rate. Additionally, we analyzed serum ApoE levels using an enzyme-linked immunosorbent assay. A total of 602 subjects (291 histologically verified LSCC patients and 311 healthy controls) were involved in this study. The genotyping was carried out using the real-time PCR. We revealed that ApoE ε3/ε3 was associated with a 1.7-fold higher probability of developing LSCC (p = 0.001), with 1.7-fold increased odds of developing LSCC without metastasis to the lymph nodes (p = 0.002) and with a 2.0-fold increased odds of developing well-differentiated LSCC (p = 0.008), as well as 1.6-fold increased odds of developing poorly differentiated LSCC development (p = 0.012). The ApoE ε2/ε4 and ε3/ε4 genotypes were associated with a 2.9-fold and 1.5-fold decrease in the likelihood of developing LSCC (p = 0.042; p = 0.037, respectively). ApoE ε3/ε4 was found associated with a 2.4-fold decreased likelihood of developing well-differentiated LSCC (p = 0.013). Conclusion: ApoE ε2/ε4 and ε3/ε4 were found to play a protective role in LSCC development, while ApoE ε3/ε3 may have a risk position in LSCC development.