Correlation between the expression of matrix metalloproteinase-9, matrix metalloproteinase-13, tissue inhibitor of metalloproteinases-1, p16 and differentiation of head and neck squamous cell carcinoma: A prospective observational study

Abstract

Introduction: The expression of matrix metalloproteinase-9 (MMP-9), MMP-13, and tissue inhibitor of metalloproteinases (TIMP-1) in head and neck squamous cell carcinoma (HNSCC) could be a useful predictor of tumour differentiation, nodal metastasis, and invasiveness. We conducted this study to ascertain the correlation between the expression of these markers and differentiation of tumour cells. Materials and Methods: A prospective observational study was conducted in a tertiary care center. Forty-three cases of proven HNSCC were recruited after obtaining informed consent. Using the surgically excised specimen, tumour differentiation and invasiveness were assessed and correlated with rates of expression of the markers. Chi-square test was done to correlate immunohistochemical (IHC) marker positivity and the degree of differentiation of the tumour, lymph node metastasis, and invasiveness. Results: MMP-9, MMP-13, and TIMP-1 were expressed in 72%, 34%, and 18% of cases, respectively. p16 expression was not found in any of the cases. MMP-13 expression correlated with poorer differentiation of the tumour ( p = 0.03), and relatively younger age at diagnosis ( p = 0.01). However, there was no correlation with lymphovascular or perineural invasion or lymph node metastasis. Discussion: In our study, MMP-13 expression correlated with poorer tumour differentiation and younger age at diagnosis, giving indirect evidence of tumour aggressiveness. IHC markers can provide additional information to prognosticate HNSCC. Identifying potential targets for newer biological therapy is essential in the Indian population as there are biological differences in cancer behavior. Increased expression of the proteolytic MMP-13 correlated with poorer differentiation of HNSCC.

Interleukin‐11/gp130 upregulates MMP‐13 expression and cell migration in OSCC by activating PI3K/Akt and AP‐1 signaling

“…Several MMPs have been investigated regarding their roles in the progression of various cancers as well as metastatic processes (Miguel et al, 2020). MMPs are endopeptidases, capable of degrading most ECM components, and are reportedly essential for tumor invasion; MMPs are not generally expressed in nontumor tissue (Soni et al, 2021). It is known that MMP‐1, ‐2, ‐3, ‐7, ‐9, and ‐14 stimulate OSCC lymph node metastasis (Miguel et al, 2020).…”

“…In our study, silencing MMP‐13 significantly reduced IL‐11‐induced migratory ability of OSCC cells. In an Indian cohort of patients with HNSCC, 72%, 34%, and 18% of cases expressed MMP‐9, MMP‐13, and tissue inhibitor of metalloproteinases (TIMP‐1), respectively; only MMP‐13 expression was significantly associated with poorer tumor differentiation, and no associations were observed between MMP‐9, MMP‐13, or TIMP‐1 with lymph node metastasis (Soni et al, 2021). The evidence indicates that targeting MMP‐13 is worthwhile in OSCC metastasis.…”

A perspective of matrix metalloproteases gene expression profile revealed by pan-cancer transcriptome and single cell data

“…This is consistent with a previous study conducted by Aparna et al, who determined that MMP1, 3, 7, 8, 10, 12, 20, and 27 genes showed multiple mutations in patients with HNSC and con rmed a positive correlation between MMP20 expression and cancer staging (21). A prospective study by Soni et al discovered an association between MMP13 expression and a low diagnostic age for HNSC (22). MMP17 has also been found to strengthen the metastasis of HNSC cells in a hypoxic environment by promoting invadopodium formation and amoeboid movement (21).…”