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Salivary Matrix Metalloproteinase (MMP)-1 as Non-Invasive Tool for The Diagnosis of Oral Squamous Cell Carcinoma (OSCC)
Abstract
OBJECTIVE: To determine the diagnostic accuracy of salivary MMP1 as non-invasive diagnostic biomarker of OSCC through conventional sandwich ELISA technique. Analytical cross-sectional study. METHODOLOGY: Individuals with clinical suspicion for OSCC (IWCS-OSCC) were included in the study after fulfilling selection criteria. Saliva samples were collected from IWCS-OSCC. To confirm OSCC, the patients were referred for biopsy. After definitive diagnosis on biopsy, patients were labeled OSCC positive or OSCC negative. The colorimetric sandwich-ELISA test was performed on saliva samples to measure the level of MMP1. Data was entered in "Statistical Package for the Social Sciences (SPSS) -16" and levels of MMP1 were correlated with the biopsy status of patient (OSCC positive or OSCC negative). RESULTS: Our sample included twice as many males as females (2.1:1) and a wide age range of 22-77years with median age of 50yrs. Of all the IWCS-OSCC 85% were OSCC +ve and 15% were OSCC-ve. Diagnostic accuracy was measured as; Area under curve (AUC) = 0.623, Sensitivity (Sn) = 50%, Specificity (Sp)= 83.3%, Positive predictive value (PPV)= 94.4%, Negative predictive value (NPV)= 22.7% CONCLUSION: MMP1 as detected by conventional sandwich-ELISA technique is not proven as an accurate diagnostic biomarker of OSCC. KEY WORDS: OSCC; MMP1; IWCS-OSCC; Sandwich-ELISA HOW TO CITE: Zaidi SJ, Riaz N, Iqbal A, Khan AA. Salivary matrix metalloproteinase (MMP)-1 as non-invasive tool for the diagnosis of oral squamous cell carcinoma (OSCC). J Pak Dent Assoc 2021;30(1):18-23.
... 9 Another issue associated with incisional biopsy is the elevated risk of metastasis resulting from the disruption to the tissue barrier. 2 The establishing of a diagnosis of OSCC at an early stage can prevent the necessity for more extensive treatment procedures by the utilisation of diagnostic tools, including biomarkers. Salivary biomarkers, which consist of DNA, RNA, and protein markers, are one of the diagnostic modalities that have a significant relevance in the field of molecular biology. ...
... 18 Vol 11, compromised individuals who are at high risk after surgical intervention. 2 In addition to having several advantages, the salivary examination also has disadvantages, including that the concentration of most analytes in the saliva is considered insufficient (100-1000 times) compared to concentrations in blood, but this is not a restriction for salivary sampling in oral cancer because biomarkers are usually produced spontaneously and locally to the tumor area. Moreover, the currently available technology is considered very sensitive for examination using salivary media. ...
Introduction: Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide and the most prevalent form of oral cancer. The five-year survival rate for OSCC varies considerably depending on the stage of the disease, ranging from 40% to 60%. The majority of cases are diagnosed at an advanced stage, resulting in a significantly reduced life expectancy. Therefore, there is a clear need for effective strategies to detect cancer at an early stage. Aim: The objective of this article is to identify the potential of matrix metalloproteinase (MMP) as a salivary biomarker for the early detection of oral squamous cell carcinoma (OSCC). Review: Saliva is considered a potential source of biomarkers for oral cancer due to its continuous contact with cancerous lesions in the oral cavity and the various enzymes, hormones, antibodies, antimicrobial constituents, and cytokines it contains. MMP is an extracellular endopeptidase enzyme present in saliva and associated with the carcinogenesis process. It has been identified as a salivary biomarker for the early detection of OSCC. The levels of several MMP proteins in the saliva of OSCC patients have been found to be elevated, including MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-12, and MMP-13. Conclusion: The increased levels of salivary MMP, which were most specifically found in OSCC patients, included MMP-1, MMP-2, MMP-3, MMP-9, MMP-10, MMP-12, and MMP-13. This suggests that MMP may be a potential salivary biomarker for the early detection of OSCC
... Choudhry et al. reported an accuracy (64%), sensitivity (71.1%), and specificity (55.3%) for serum MMP-1 to predict the presence of oral squamous cell carcinoma [57]. Zaidi et al. found an accuracy (62%), sensitivity (50%), and specificity (83.3%) for salivary MMP-1 to correctly diagnose the oral squamous cell carcinoma [69]. In order to create a sensitive biosensor for detecting MMP-1, Zhong et al. created a commercial test strip. ...
Oral cancer is one of most common noncommunicable diseases that imposed significant burden on healthcare around the globe including India. Several molecular markers have been extensively researched for their potential as diagnostic and prognostic biomarkers for oral cancer. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) found to play a crucial role in cytoskeleton dynamics and thus tumor growth and metastasis. The present study aims to analyze the MMP (MMP-1, MMP-3, MMP-9, and MMP-13) and TIMP (TIMP-1 and TIMP-3) expression in the oral cancer patients as compared to healthy controls. We also aim to compare the diagnostic accuracy of MMPs and TIMPs on enzyme-linked immunosorbent assay (ELISA) with respect to the immunohistochemistry (IHC). A total of 15 oral cancer patients and 14 healthy controls were enrolled in this study. Blood sample from oral cancer patients and healthy controls was obtained to analyze the MMP and TIMP expression levels in serum sample using ELISA. Tumor tissue sample from patients for IHC analysis was obtained by biopsy under local anesthesia. Data were compared between ELISA and IHC for sensitivity and specificity analysis. The mean age of the patients was 47.07 ± 15.74 years with the highest incidence of disease found in male gender (86.7%). MMPs and TIMPs exhibited higher expression in oral cancer patients as compared to healthy controls and the difference was statistically significant in case of MMP-13. MMPs and TIMPs showed stronger expression at advanced stages of cancer on IHC with MMP-9 exhibiting the highest expression level. The highest sensitivity and specificity on ELISA with respect to IHC were exhibited by the MMP-3 followed by MMP-13, TIMP-1, TIMP-3, and MMP-1. MMP-3 and MMP-13 were found to be reliable in terms of diagnostic marker for oral cancer as they found to have the highest sensitivity and specificity on ELISA with respect to IHC. MMP-9 was found to be reliable as a prognostic marker as it expresses highest on IHC at advanced stages of oral cancer.
Oral squamous cell carcinoma (OSCC) accounts for >90% of cases of oral cancer, including cancer at the lip and oral cavity and cancer at the oropharynx. Most OSCCs develop from oral potentially malignant disorders (OPMDs), which consist of heterogeneous lesions with different malignant transformation potentials that make early detection of OSCC a challenge. Using a targeted mass spectrometry-based assay to compare multiple candidate proteins, we previously identified matrix metalloproteinase-1 (MMP-1) as one of the most promising salivary OSCC biomarkers. To explore the clinical utility of MMP-1 in OSCC detection, we developed an in-house, sensitive enzyme-linked immunosorbent assay (ELISA) for measuring MMP-1 content, and tested it on saliva samples from 1160 subjects (313 healthy controls, and 578 OPMD and 269 OSCC patients) collected at two medical centers. Salivary MMP-1 levels measured by our in-house ELISA significantly discriminated OSCC patients from non-cancerous groups. A receiver operating characteristic curve analysis showed that MMP-1 was effective in separating non-cancer groups from patients with OSCCs at the oral cavity. Additionally, salivary MMP-1 levels in oral cavity cancer patients were highly correlated with tumor progression (tumor size, lymph node metastasis, and overall stage). Collectively, our results indicate that salivary MMP-1 is an effective biomarker for OSCC that can be sensitively detected using our newly developed ELISA. The newly developed MMP-1 ELISA may be used as a new adjunctive tool to aid in detecting and monitoring OSCC.
Objective:
To compare the salivary MMP - 9 concentration among subjects with oral squamous cell carcinoma (OSCC), oral potentially malignant disorders (OPMD), tobacco users, and control groups.
Materials and methods:
A total of 88 subjects were enrolled and divided into four study groups viz., OSCC (n=24), OPMD (n=20), tobacco habits (n=22), and healthy controls (n=22). All subjects gave unstimulated saliva samples for the evaluation MMP - 9 by ELISA kit. Demographic information like age, gender, type of tobacco, and duration of the habit were recorded.
Results:
Subjects with OSCC and OPMD had significantly higher mean MMP-9 levels than subjects with tobacco habits and control groups (P<0.001). Also, poorly differentiated OSCC group had significantly higher mean saliva MMP-9 than moderate and well-differentiated OSCC. The optimal cut-off point was 214.37 ng/mL with a sensitivity of 100% and specificity of 59% for OSCC versus the control group. The optimal cut-off point was as 205.87 ng/mL with a sensitivity of 100% and a specificity of 54% for OPMD versus the control group.
Conclusion:
The data obtained from this study indicated that OSCC and OPMD had an increased level of salivary MMP-9. Salivary MMP-9 could be a useful, non-invasive adjunct technique in the diagnosis, treatment, and follow-up of OSCC and OPMD.
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Background:
Delayed diagnosis of Oral Cancer (OC) can mean a difference in quality and expectancy of life for the patient. This delay could be from the healthcare side, or more importantly from the patient's side. Globally, there are studies enumerating the causes for delays from the patients' side in seeking healthcare for Oral Cancer; however, no similar research is found in the context of Pakistan. This study endeavoured to understand the health seeking behaviour, reasons for delay in consultation and the impact on OC patients' lives.
Methods:
In-depth interviews were conducted with randomly selected OC patients at a private sector tertiary care facility in Islamabad (who met the inclusion criteria of having successfully been treated for Oral Cancer) which caters to the most diverse population for the treatment of Oral Cancer. Theoretical saturation was achieved at 14 interviews. All participants gave verbal consent for participation, which was recorded prior to the interviews.
Results:
Patients (age range 43-68 years) had received the surgical treatment and radiation. The reported delay before seeking a proper medical advice ranged from 1 month to 2 years. Lack of awareness about OC risk factors, symptoms, and whom to approach for treatment were the main reasons. Most respondents relied on self-treatment considering the non-healing wound/ulcer to be a minor issue until they were advised a consultation with a specialist. Treatment started within 1-3 months after a confirmed diagnosis on biopsy. The reported average expenditure on treatment was US$5000-10,000, mostly covered through a private health insurance and others borrowed the money.
Conclusion:
A socio-behavioural change campaign for the general population can result in earlier presentation of the OC, minimizing the financial burden on the patient as well as the health system, and improving the quality of life of the patients.
Production of antibodies to erythropoietin-stimulating drugs is an important problem of therapy with recombinant human erythropoietin (EPO). It leads to changes in the pharmacokinetic profile and decreased therapeutic efficiency. Upon long-term treatment with EPO preparations, neutralizing antibodies can result in rare cases, thus leading to complete pure red cell aplasia. Hence, detection of antibodies to EPO is an important stage in the assessment of the drug immunogenicity in preclinical and clinical studies, as well as during the treatment with EPO. We have compared colorimetric and chemiluminescent ELISA tests for detection of IgG antibodies to human EPO with 3,3’,5,5’-tetramethylbenzidine – hydrogen peroxide and luminol -hydrogen peroxide detection systems, respectively. Аntibodies to human EPO were determined in blood serum samples of experimental animals, i.e., rabbits and guinea pigs following their immunization withdifferent doses of pegylated human recombinant EPO-beta subcutaneously or intravenously. The affinitypurified rabbit polyclonal antibodies to human EPO were used as a reference material. The effects of hydrogen peroxide and luminol concentrations upon sensitivity of a chemiluminescent method were also studied. We have shown a 1.5-2-fold increase in sensitivity when using 4-iodophenol for amplification of chemiluminescence. A comparison of the chemiluminescence intensity with time has demonstrated a better stability for the substrate mixture prepared on borate buffer. A decrease in chemiluminescence signal with time was proportional to the decrease in background signal, thus rendering stability of the signal/background ratio for 3 to 30 minutes. Due to optimizing the substrate mixture composition and conditions of chemiluminescence recording, the reached detection limits for colorimetric and chemiluminescent ELISA’s were, respectively, 0.6 ng/ml and 0.08 ng/ml. The measurement range was extended by more than 20 times for chemiluminescent ELISA. The chemiluminescent ELISA for anti-erythropoietin antibody detection showed a 1.9 to 2.6-fold increase in sensitivity for rabbit serum, and 1.8 to 8.9-fold for guinea pigs serum. Good correlation of results was found for quantitative detection of antibodies in rabbit sera using the two methods (R = 0.981). Thus, chemiluminescent ELISA allowed develop a more sensitive detection technique of IgG antibodies to human erythropoietin.
Biopsy is the removal of tissue from a living person for microscopic examination to confirm or to establish the diagnosis of a disease The purpose of this article is to review those skills, to discuss new developments in this area, and to highlight some of the potential pitfalls that may occur in taking a biopsy and methods available to avoid them. We feel it will be of value to both general dental practitioners and junior hospital staff. Problems related to specific areas will be covered including apical lesions and those associated with the dental hard tissues.
The oral squamous cell carcinoma (OSCC) is one of the most common epithelial malignancies with significant morbidity and mortality. Recent observations indicate that the clinical and histological appearance of oral mucosa may not truly depict the damage occurring at the genetic level. This phenotypic and genotypic disparity may account in part for the failure to establish effective screening and surveillance protocols, based on the traditional clinical and microscopic examination. The tumor markers are playing an increasingly important role in cancer detection and management. These laboratory-based tests are potentially useful in screening for early malignancy, aiding in cancer diagnosis, determining prognosis, surveillance following curative surgery for cancer, up-front predicting drug response or resistance, and monitoring therapy in advanced disease. A systematic review of the literature was performed based on the English titles listed in the PubMed, EBSCO, Cochrane, Science Direct, ISI web Science, and SciELO databases using the keywords. Abstracts and full-text articles were assessed. This article may help to identify the potential biomarkers for screening and the molecular pathology analysis in the high-risk patients with the OSCC.
Oral squamous cell carcinoma (OSCC) accounting for about 90% of malignant oral lesions is the 6th most common malignancy worldwide. Diagnostic delay may contribute to dismal survival rate therefore, there is a need for developing specific and sensitive biomarkers to improve early detection. Hungarian population occupies the top places of statistics regarding OSCC incidence and mortality figures therefore, we aimed at finding potential salivary protein biomarkers suitable for the Hungarian population. In this study we investigated 14 proteins which were previously reported as significantly elevated in saliva of patients with OSCC. In case of IL-1α, IL-1β, IL-6, IL-8, TNF-α and VEGF a Luminex-based multiplex kit was utilized and the salivary concentrations were determined. In case of catalase, profilin-1, S100A9, CD59, galectin-3-bindig protein, CD44, thioredoxin and keratin-19, SRM-based targeted proteomic method was developed and the relative amount of the proteins was determined in the saliva of patients with OSCC and controls. After several rounds of optimization and using stable isotope-containing peptides, we developed an SRM-based method for rapid salivary protein detection. The validation of the selected potential biomarkers by ELISA revealed salivary protein S100A9 and IL-6 as useful protein biomarkers for OSCC detection improving the diagnostic accuracy for OSCC in the Hungarian population.A noninvasive diagnostic method to detect biomarkers useful for the early diagnosis of OSCC was developed. This can be an attractive strategy in screening saliva samples collected in a nation-wide multi-centric study in order to decrease morbidity, mortality, to enhance survival rate and to improve quality of life. The heterogeneity of protein biomarkers found in different ethnic groups presented in the literature highlights the importance of identification of population-tailored protein biomarkers.
Objective
: Oral squamous-cell carcinoma (OSCC) accounts for >90% of oral cancers affecting adults mostly between the fourth to seventh decades of life. The most common OSCC treatment is concomitant chemoradiotherapy (CCRT) having both loco-regional and distant control, but CCRT has acute and chronic toxic effects on adjacent normal tissue. This study aimed to determine the side effects of CCRT on the oral mucosa and to characterize the clinicopathology of oral lesions in patients with OSCC.
Methods
This descriptive, cross-sectional study was certified by the Ethical Review Committee (UHS/Education/126-12/2728) of the University of Health Sciences, Lahore, Pakistan. OSSC patients (n=81) with various histological subtypes, grades, and stages were recruited, and findings on their oral examination were recorded. These patients received 70, 90, and 119 Gy of radiotherapy dosages in combination with the chemotherapy drugs cisplatin and 5-fluorouracil. Data were analyzed using SPSS 20.0.
Results
: The most common presentation of OSCC was a nonhealing ulcer (63%) involving tongue (55.6%). Clinical findings included mucositis (92.6%) and xerostomia of mild, moderate, and severe degrees in 11.1%, 46.9%, and 35.8% cases, respectively. Ulcers (87.7%), palpable lymph nodes (64.2%), limited mouth opening (64.2%) and fistula (40.7%) were also observed. In females, the association of radiotherapy dosage with limited mouth opening, xerostomia, and histological grading was statistically significant (P<0.05). The association of chemotherapy drugs with xerostomia (P=0.003) was also statistically significant.
Conclusions
: CCRT induced mucositis, xerostomia, and trismus in patients with OSCC.
Background
Colorectal cancer (CRC) screening programs based on the fecal occult blood test (FOBT) reduce CRC mortality. We carried out an observational prospective study to determine the accuracy of immunochemical FOBTs for the detection of CRC in individuals at average risk for the disease.
Methods
This population-based study was performed between April 2015 and January 2016 in two gastroenterology referral centers in Southern Brazil. It included 1039 average-risk volunteers aged 50-75 years who were symptom-free for colonic disease. Participants underwent OC-Light immunochemical fecal occult blood test (i-FOBT, EIKEN chemical Co., Tokyo, Japan) as well as screening colonoscopy.
Results
Nine hundred forty-eight (91.2%) of the 1039 participants completed and returned the i-FOBT (95% confidence interval [CI] 89.4-92.9). Among the 73 participants with a positive i-FOBT who underwent colonoscopy, advanced CRC was detected in 9 (12.3%). Two (2.7%) early CRCs, 7 (9.5%) high-grade dysplasia adenomas and 25 (34.2%) low-grade dysplasia adenomas were also diagnosed. Among the 243 negative i-FOBT cases who underwent colonoscopy, one (0.4%) advanced CRC and 91 (37.6%) low-grade dysplasia adenomas were detected. The detection rate of CRC considering the whole screened population (n=1039) was 1.05% (11/1039).
Conclusions
The i-FOBT test in the CRC screening programs in Brazil showed a high compliance and high detection rates for cancers and high-risk adenomas. The i-FOBT test is feasible for CRC screening in an average-risk population.
Objectives
To determine the frequency of delayed diagnosis of oral squamous cell carcinoma in our setup; highlighting factors responsible for any delay and their possible relevance to demographic and diagnostic features.
Methods
This cross sectional study of six months duration was conducted in the Oral and Maxillofacial Surgery Department of the Armed Forces Institute of Dentistry, Rawalpindi, Pakistan. A total of 246 patients, both male and female, having a biopsy proven definitive diagnosis of OSCC were included using a consecutive sampling technique. Delay in diagnosis was assessed from the stated period of time from when the patient first noticed symptoms of disease until a definitive diagnosis was made. We concluded delayed diagnosis if this was more than 40 days.
Results
The ages of patients ranged from 27 to 60 years with a mean of 46.7 ± 10.2 years and a marked male predominance (3.7:1). Delayed diagnosis was observed in 91.5% of cases. However, statistically no significant differences were found with age, gender, marital, education status, household income and time of biopsy.
Conclusion
Our primary finding of delayed diagnosis with no prior contact with any health care professional clearly reflects a need of taking urgent measures to avoid serious impacts on morbidity and mortality associated with OSCC.
Significance
Oral squamous cell carcinoma (OSCC) accounts for 90% of oral cancers, and earlier detection efficiently increases the survival rate. Here, we used a comprehensive literature review to select candidates and used LC-multiple reaction monitoring-MS to qualitatively and quantitatively measure target proteins in saliva samples from individuals of the at-risk population in Taiwan. Statistical analysis of the results establishes a four-protein panel sufficient to detect 88.6% of early-stage patients and 91.6% of all patients with 80.4% specificity. This panel can also be used to evaluate the risk of malignant progression from high-risk oral potential malignant disorder. Our study offers a practical foundation for clinical trials examining the ability of this panel to enable early detection of OSCC, risk assessment for cancer development, and treatment monitoring.
Oral cancer is the sixth most common malignancy in the world. Oral cancer is of major concern in Southeast Asia primarily because of the prevalent oral habits of betel quid chewing, smoking, and alcohol consumption. Despite recent advances in cancer diagnoses and therapies, the 5.year survival rate of oral cancer patients has remained at a dismal 50% in the last few decades. This paper is an overview of the various etiological agents and risk factors implicated in the development of oral cancer.
Oral squamous cell carcinoma (OSCC) has a remarkably high incidence worldwide, and a fairly serious prognosis, encouraging further research into advanced technologies for noninvasive methods of making early diagnoses, ideally in primary care settings.
Our purpose was to examine the validity of using advanced noninvasive technologies in diagnosis of OSCC by identifying and evaluating relevant published reports.
Data source
MEDLINE, EMBASE, and CINAHL were searched to identify clinical trials and other information published between 1990 and 10 June 2014; the searches of MEDLINE and EMBASE were updated to November 2014. Study selection: Studies of noninvasive methods of diagnosing OSCC, including oral brush biopsy, optical biopsy, saliva-based oral cancer diagnosis, and others were included.
Data extraction
Data were abstracted and evaluated in duplicate for possible relevance on two occasions at an interval of 2 months before being included or excluded.
Data synthesis
This study identified 163 studies of noninvasive methods for diagnosing OSCC that met the inclusion criteria. These included six studies of oral brush biopsy, 42 of saliva-based oral diagnosis, and 115 of optical biopsy. Sixty nine of these studies were assessed by the modified version of the QUADAS instrument. Saliva-based oral cancer diagnosis and optical biopsy were found to be promising noninvasive methods for diagnosing OSCC.
The strength of evidence was rated low for accuracy outcomes because the studies did not report important details required to assess the risk for bias.
It is clear that screening for and early detection of cancer and pre-cancerous lesions have the potential to reduce the morbidity and mortality of this disease. Advances in technologies for saliva-based oral diagnosis and optical biopsy are promising pathways for the future development of more effective noninvasive methods for diagnosing OSCC that are easy to perform clinically in primary care settings.
The family of human matrix metalloproteinases (MMPs) comprises several tightly regulated classes of proteases. These enzymes and their specific inhibitors play important roles in tumour progression and the metastatic process by facilitating extracellular matrix degradation. As scientific understanding of the MMPs has advanced, therapeutic strategies focusing on blocking these enzymes by matrix metalloproteinase inhibitors have rapidly developed. Low molecular weight tissue inhibitors of matrix metalloproteinase (TIMPs) represent a new therapeutic approach for the treatment of individual types of cancer. This paper aims to briefly summarize current knowledge about the role of MMPs in select non- tumorous lesions, tumor invasion and metastasis. The perspectives in therapeutic intervention in cancer are also mentioned. The role of MMPs in diagnosis and prognosis of colorectal and thyroid cancer is discussed in detail.
Analysis of 23 published transcriptome studies allowed us to identify nine genes displaying frequent alterations in HNSCC (FN1, MMP1, PLAU, SPARC, IL1RN, KRT4, KRT13, MAL, and TGM3). We aimed to independently confirm these dysregulations and to identify potential relationships with clinical data for diagnostic, staging and prognostic purposes either at the tissue level or in saliva rinse.
For a period of two years, we systematically collected tumor tissue, normal matched mucosa and saliva of patients diagnosed with primary untreated HNSCC. Expression levels of the nine genes of interest were measured by RT-qPCR in tumor and healthy matched mucosa from 46 patients. MMP1 expression level was measured by RT-qPCR in the salivary rinse of 51 HNSCC patients and 18 control cases.
Dysregulation of the nine genes was confirmed by the Wilcoxon test. IL1RN, MAL and MMP1 were the most efficient diagnostic markers of HNSCC, with ROC AUC > 0.95 and both sensitivity and specificity above 91%. No clinically relevant correlation was found between gene expression level in tumor and T stage, N stage, tumor grade, global survival or disease-free survival. Our preliminary results suggests that with 100% specificity, MMP1 detection in saliva rinse is potentially useful for non invasive diagnosis of HNSCC of the oral cavity or oropharynx, but technical improvement is needed since sensitivity was only 20%.
IL1RN, MAL and MMP1 are prospective tumor diagnostic markers for HNSCC. MMP1 overexpression is the most promising marker, and its detection could help identify tumor cells in tissue or saliva.
Oral squamous cell carcinoma (OSCC) is the most commonly occurring malignant tumor in South East Asian region. It is a major cause of morbidity and mortality.. Our sample size is comprised of 80 patients with histologically proven cases of OSCC of both genders were included in this study. In present study, most predominant site of occurrence of OSCC was buccal mucosa 34(50%) nevertheless least cases were found affected at floor of the mouth 1(1.5%). Of the total sample size maximum number of cases were reported between the age group of 31-60 years, 53(77.9%) and showed higher predilection towards male gender. However the OSCC of the hard palate and upper alveolar mucosa were specifically found more in female. Almost all of these patients gave a positive history of betal chewing. This has now become major public health problem, and awareness to the masses is necessary to control the rising rate of oral malignant disease in the country.
Background:
MMP-1 (Matrix metalloproteinase-1) promotes carcinogenesis and distant metastasis in different cancers. Regulation of MMP-1 could occur at multiple levels: epigenetically, post-transcriptionally, or post-translationally. An increasing body of evidence supports that the cytoplasmic transcription factor STAT3 (signal transducer and activator of transcription 3) is activated constitutively in a variety of cancers wherein it significantly affects the growth of tumors and also facilitates metastasis. In addition, STAT3 has been found to regulate nuclear activity pro-inflammatory transcriptional factor, NF-κB signaling, especially, the alternative one (RelB/p100) by directly interacting with them METHOD AND RESULTS: In this proof of concept study, we tested the hypothesis that STAT3 interacts with RelB to promote tumor invasion by positively regulating MMP-1 in colon cancer. We found that RelB and STAT3 were constitutively localized in the nucleus of colon cancer in surgically-resected specimens with use of Western blot analysis, which was further confirmed by immunofluorescence (IF) staining in colon carcinoma cell line HT29. We further observed that STAT3/RelB knockdown resulted in reduced MMP-1. Our results from chromatin immunoprecipitation studies further established that association between RelB and MMP-1 promoter decreased when STAT3 was depleted, and conversely, STAT3 association with MMP-1 decreased with the knockdown of RelB.
Conclusion:
These results suggest that STAT3 and ReB constitute a minimal activator complex for positive regulation of MMP-1 in colon cancer.
AimTo compare the performance of history and examination findings combined with transvaginal ultrasound (TVS) ‘soft marker’ evaluation of ovarian mobility for the prediction of fixed ovaries secondary to endometriosis at laparoscopy. Methods
This was a prospective observational study performed at the University Gynecology unit, National Hospital of Colombo Sri Lanka. Women who were scheduled for laparoscopic assessment of their pelvis to investigate subfertility or chronic pelvic pain were enrolled. All women underwent history evaluation for dysmenorrhea and dyspareunia, vaginal examination and detailed presurgical TVS. TVS was used to assess ‘soft marker’ of ovarian mobility. ‘Fixed’ ovaries on ultrasound were defined as one or other of the ovaries being fixed or adherent to the internal iliac artery or pelvic sidewall laterally or to the uterus medially. These findings were compared with ‘fixed’ ovaries confirmed at laparoscopy. ResultsA total of 106 patients were analyzed. Mean age was 33.3 years (standard deviation, 5.1). Sensitivity, specificity, positive and negative predictive values of each of the screening methods against laparoscopy in detecting endometriosis were as follows: dyspareunia, 45.9%, 76.8%, 51.5% and 72.6%; dysmenorrhea, 75.7%, 69.6%, 57.1% and 84.2%; positive vaginal examination, 73%, 88.4%, 77.1% and 85.9%; fixed ovaries with TVS, 78.4%, 94.2%, 87.9% and 89%; and a combination of history, examination findings and detection of fixed ovaries in TVS, 91.9%, 60.9%, 55.7% and 93.3%, respectively. ConclusionA combination of clinical and TVS-based ‘soft marker’ of ovarian mobility provides a valid method for identifying fixed ovaries secondary to endometriosis.
The matrix metalloproteinases (MMP) cause degradation of the extracellular matrix and basement membranes, and thus may play a key role in cancer development.
In our search for biomarkers for oral squamous cell carcinomas (OSCC), we compared primary OSCC, oral dysplasia and control subjects with respect to: (i) expression of MMP1, MMP3, MMP10, and MMP12 in oral epithelial tissue using Affymetrix U133 2.0 Plus GeneChip arrays, followed by quantitative reverse transcription-PCR (qRT-PCR) for MMP1, and (ii) determination of MMP1 and MMP3 concentrations in saliva.
MMP1 expression in primary OSCC (n = 119) was >200-fold higher (P = 7.16 × 10(-40)) compared with expression levels in nonneoplastic oral epithelium from controls (n = 35). qRT-PCR results on 30 cases and 22 controls confirmed this substantial differential expression. The exceptional discriminatory power to separate OSCC from controls was validated in two independent testing sets (AUC% = 100; 95% CI: 100-100 and AUC% = 98.4; 95% CI: 95.6-100). Salivary concentrations of MMP1 and MMP3 in OSCC patients (33 stage I/II, 26 stage III/IV) were 6.2 times (95% CI: 3.32-11.73) and 14.8 times (95% CI: 6.75-32.56) higher, respectively, than in controls, and displayed an increasing trend with higher stage disease.
Tumor and salivary MMPs are robust diagnostic biomarkers of OSCC.
The capacity of MMP gene expression to identify OSCC provides support for further investigation into MMPs as potential markers for OSCC development. Detection of MMP proteins in saliva in particular may provide a promising means to detect and monitor OSCC noninvasively.
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