scholarly journals Oncofetal Protein CR-1 in a new clinical role: a potential tumor marker for Oral Squamous Cell Carcinoma

2019 ◽  
Author(s):  
Jain Anu ◽  
Mallupattu Sumanth Kumar ◽  
Thakur Reetu ◽  
Mohindra Satyawati ◽  
Bal Amanjit ◽  
...  

AbstractPURPOSECR-1 (CR-1) is an oncofetal protein with its role as a key factor in early process of carcinoma has been evaluated in cases of various cancers. However, very few studies have reported its role in oral cancers, which is the sixth most common cancer around the world, particularly with high prevalence in developing countries. Oral squamous cell carcinoma (OSCC) is the most predominant (90%) of all the histological types of oral cancer. Late detection, associated with increased morbidity and mortality, is mainly attributed to non-availability of a suitable biomarker for the disease. In the present pilot study we have evaluated the role of soluble CR-1, in serum as a potential tumor marker for OSCC.METHODSCR-1 was estimated using sandwich ELISA in serum samples of 50 biopsy proven OSCC patients (pre and post treatment) along with age and gender matched healthy controls. Immunohistochemistry was also done in corresponding tumor tissue sections to check the expression of CR-1.RESULTSPre-treatment CR-1 was found to be 2.25 fold higher in serum of OSCC patients as compared to control (p<0.0001***), which was reduced to 1.6 folds post treatment (p=0.0006***). CR-1 levels were comparatively higher in early stage of disease. Upon IHC 80% of the cases were found to be positive for CR-1.CONCLUSIONThis study provides evidence that serum levels of CR-1 are elevated in patients of Oral Squamous Cell Carcinoma, which decrease post treatment. Also, the association of expression of protein with tumor progression predicts CR-1 as a molecule that can be further evaluated as a potential tumor maker in OSCC.

2012 ◽  
Vol 13 (5) ◽  
pp. 671-675 ◽  
Author(s):  
Jude J Balan ◽  
BR Premalatha

ABSTRACT Background The mortality and morbidity associated with oral squamous cell carcinoma (OSCC) can be greatly reduced if tumor markers which can detect OSCC at an early stage are available. The use of saliva as an alternative to blood could provide a substantial advantage in sampling convenience. Cancer antigen 125 (CA 125) is a tumor-associated antigen found to be increased in epithelial tumors like oral, breast and ovarian cancers. Aim To determine whether salivary CA 125 levels are increased significantly in OSCC patients than the control group. Materials and methods Sixty OSCC patients and 60 healthy controls were taken for the study. Saliva samples from both the groups were collected, centrifuged and supernatant fluid were subjected to ELISA for assessment of CA 125. The mean salivary CA 125 values of OSCC patients and control group were statistically analyzed using Mann-Whitney U-test. Results The mean salivary CA 125 concentration of OSCC group was 320.25 and that of control group was 33.14. Thus, CA 125 was found to be significantly increased in the saliva of OSCC patients than the control group (p < 0.001). Also, there was significant increase in the CA 125 levels as the stage of OSCC increased. Conclusion The convenience, reliability and noninvasive nature of salivary CA 125 testing makes it a feasible adjunctive diagnostic tool for detection of OSCC. How to cite this article Balan JJ, Rao RS, Premalatha BR, Patil S. Analysis of Tumor Marker CA 125 in Saliva of Normal and Oral Squamous Cell Carcinoma Patients: A Comparative Study. J Contemp Dent Pract 2012;13(5):671-675.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Chi T. Viet ◽  
Gary Yu ◽  
Kesava Asam ◽  
Carissa M. Thomas ◽  
Angela J. Yoon ◽  
...  

Abstract Background Oral squamous cell carcinoma (OSCC) is a capricious cancer with poor survival rates, even for early-stage patients. There is a pressing need to develop more precise risk assessment methods to appropriately tailor clinical treatment. Genome-wide association studies have not produced a viable biomarker. However, these studies are limited by using heterogeneous cohorts, not focusing on methylation although OSCC is a heavily epigenetically-regulated cancer, and not combining molecular data with clinicopathologic data for risk prediction. In this study we focused on early-stage (I/II) OSCC and created a risk score called the REASON score, which combines clinicopathologic characteristics with a 12-gene methylation signature, to predict the risk of 5-year mortality. Methods We combined data from an internal cohort (n = 515) and The Cancer Genome Atlas (TCGA) cohort (n = 58). We collected clinicopathologic data from both cohorts to derive the non-molecular portion of the REASON score. We then analyzed the TCGA cohort DNA methylation data to derive the molecular portion of the risk score. Results 5-year disease specific survival was 63% for the internal cohort and 86% for the TCGA cohort. The clinicopathologic features with the highest predictive ability among the two the cohorts were age, race, sex, tobacco use, alcohol use, histologic grade, stage, perineural invasion (PNI), lymphovascular invasion (LVI), and margin status. This panel of 10 non-molecular features predicted 5-year mortality risk with a concordance (c)-index = 0.67. Our molecular panel consisted of a 12-gene methylation signature (i.e., HORMAD2, MYLK, GPR133, SOX8, TRPA1, ABCA2, HGFAC, MCPH1, WDR86, CACNA1H, RNF216, CCNJL), which had the most significant differential methylation between patients who survived vs. died by 5 years. All 12 genes have already been linked to survival in other cancers. Of the genes, only SOX8 was previously associated with OSCC; our study was the first to link the remaining 11 genes to OSCC survival. The combined molecular and non-molecular panel formed the REASON score, which predicted risk of death with a c-index = 0.915. Conclusions The REASON score is a promising biomarker to predict risk of mortality in early-stage OSCC patients. Validation of the REASON score in a larger independent cohort is warranted.


2022 ◽  
Vol 2 ◽  
Author(s):  
Rasheed Omobolaji Alabi ◽  
Alhadi Almangush ◽  
Mohammed Elmusrati ◽  
Antti A. Mäkitie

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide and its incidence is on the rise in many populations. The high incidence rate, late diagnosis, and improper treatment planning still form a significant concern. Diagnosis at an early-stage is important for better prognosis, treatment, and survival. Despite the recent improvement in the understanding of the molecular mechanisms, late diagnosis and approach toward precision medicine for OSCC patients remain a challenge. To enhance precision medicine, deep machine learning technique has been touted to enhance early detection, and consequently to reduce cancer-specific mortality and morbidity. This technique has been reported to have made a significant progress in data extraction and analysis of vital information in medical imaging in recent years. Therefore, it has the potential to assist in the early-stage detection of oral squamous cell carcinoma. Furthermore, automated image analysis can assist pathologists and clinicians to make an informed decision regarding cancer patients. This article discusses the technical knowledge and algorithms of deep learning for OSCC. It examines the application of deep learning technology in cancer detection, image classification, segmentation and synthesis, and treatment planning. Finally, we discuss how this technique can assist in precision medicine and the future perspective of deep learning technology in oral squamous cell carcinoma.


2020 ◽  
Author(s):  
Koel Mukherjee ◽  
Debpali Sur ◽  
Abhijeet Singh ◽  
Sandhya Rai ◽  
Neeladrisingha Das ◽  
...  

AbstractRetrotransposons are sequences which transpose within genomes using RNA as an intermediate. Long INterpersed Element-1 (LINE1 or L1) is the only active retrotransposon occupying around 17% of the human genome with an estimated 500,000 copies. An active L1 encodes two proteins (L1ORF1p and L1ORF2p); both of which are critical in the process of retrotransposition. In-order to propagate to the nextgeneration, L1s remain active in germ tissues and at an early stage of development. Surprisingly, by some unknown mechanism, L1 also shows activity in certain parts of the normal brain and many cancers. L1 activity is generally determined by assaying L1ORF1p because of its high expression and availability of the antibody. However, due to its lowerexpression and the unavailability of a robust antibody, detection of L1ORF2p has been limited. L1ORF2p is the crucial protein in the process of retrotransposition as it provides endonuclease and reverse transcriptase (RT) activity. Here, we report a novel human L1ORF2p antibody generated using an 80-amino-acid stretch from the RT domain, which is highly conserved among different species. The antibody detects significant L1ORF2p expression in murine germ tissues and human oral squamous cell carcinoma (OSCC) samples. This particular cancer is prevalent in India due to excessive use of tobacco. Here, using our in-house antibodies against L1 proteins, we show that more than fifty percent of samples are positive for L1 proteins. Overall, we reported a novel L1ORF2p antibody that detects L1 activity in germ tissues and OSCC


Oral Diseases ◽  
2019 ◽  
Vol 26 (7) ◽  
pp. 1357-1365 ◽  
Author(s):  
Patrícia Carlos Caldeira ◽  
Andrea María López Soto ◽  
Maria Cássia Ferreira Aguiar ◽  
Carolina Castro Martins

2016 ◽  
Vol 21 (1) ◽  
pp. 135-141 ◽  
Author(s):  
Andre Peisker ◽  
Gregor Franziskus Raschke ◽  
Arndt Guentsch ◽  
Paul Luepke ◽  
Korosh Roshanghias ◽  
...  

Head & Neck ◽  
2006 ◽  
Vol 29 (1) ◽  
pp. 3-11 ◽  
Author(s):  
Ana Capote ◽  
Veronica Escorial ◽  
Mario F. Muñoz-Guerra ◽  
Francisco J. Rodríguez-Campo ◽  
Carlos Gamallo ◽  
...  

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17572-e17572
Author(s):  
Daniel Sanghoon Shin ◽  
Eri Srivatsan ◽  
Hassan Nasser ◽  
Anela Tosevska ◽  
Jonathan Jacobs ◽  
...  

e17572 Background: Natural botanical drugs, such as curcumin, resveratrol and related flavonoids, are under clinical studies. Previous pilot study of curcumin, a polyphenol, for normal and patients with oral squamous cell carcinoma (OSCC) showed significant inhibition of inflammatory cytokines in saliva. Phase I investigation was performed on APG-157 to evaluate the potential utility an as oral drug for the treatment of OSCC. Methods: A double-blind, randomized, placebo-controlled phase I clinical trial was conducted with a botanical preparation containing a combination of curcumin related polyphenol molecules (pharmaceutical name APG-157). 12 Subjects with oral cancer and 13 normal control subjects were recruited. Two doses of the drug, 3x100 mg and 3x200 mg, were tested. The drug was administered orally each hour for 3 consecutive hours. Blood and saliva were collected pre-treatment and 1, 2, 3, and 24 hours post-treatment. Salivary cells and supernatants were analyzed for the expression of cytokines by multiplex ELISA and microbial content by 16S RNA sequence. Pre- and post-treatment tumor biopsies of one subject were studied for expression using the RNA seq and immunofluorescence (IF). Results: This study did not reveal any toxicity and there was a dose dependent inhibition of inflammatory cytokines, IL-1β, TNF-alpha and IL-8 in the salivary supernatant of cancer subjects treated with the drug. Tumor RNA-seq revealed down regulation of gene ontologies of cell adhesion, cell cycle and cell division and up regulation of generation of precursor metabolite/energy in the post-treatment tumor sample. Microbiome study showed significant decrease in Bacterioides after 24 hours of treatment. There was also a trend of decreasing Bacteroides among other cancer subjects treated with APG-157. IF showed a marked increase in the number of CD4, CD8 T cells in post-treatment tumor. PD-L1 expression was up-regulated in the post-treatment tumor sample. Conclusions: APG-157 is found to be safe and toxicity was not observed. The drug has shown a decrease in inflammatory cytokines. Moreover, there was a markedly increased CD4, CD8 T cells infiltration on a subject and decreased Bacteriodes microbial population after APG-157 treatment suggesting that it might have potential synergistic effect with immune checkpoint blockade immunotherapy. Decreased expression of cell growth related genes and increased expression of growth inhibitory genes pointed to a potential anti-tumor activity of APG-157.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15548-e15548
Author(s):  
Ritvi K Bagadia ◽  
Vishal Uchila Shishir Rao ◽  
Ajay Balakrishnan ◽  
Abhijith George ◽  
Prashant Kumar

e15548 Background: Around 90% of cancer-related mortalities are caused by tumor metastasis. CTC clusters, which constitute an intermediate stage of metastasis, have not been studied extensively in head & neck cancers. The mortality rate of oral cancers remains alarmingly high, despite multimodality treatment. The aim of the study is to identify the presence of CTC clusters in patients with Oral Squamous Cell Carcinoma (OSCC) and to correlate their presence with clinical and pathological factors. Methods: Fifty patients diagnosed with histologically proven OSCC, treatment naïve, and underwent surgery at HCG Cancer Centre, Bangalore, were consented and enrolled in the study. An IRB-approved protocol allowed for the collection of 10 ml of blood from central (jugular) and peripheral veins intra-operatively, prior to tumor removal. The culturing of CTC clusters was done using ellipsoidal microwell plates maintained at hypoxic conditions, at the Institute of Bioinformatics, Bangalore. After fourteen days of culturing, the cells were fixed and stained for DAPI, Pan-CK and CD45. The CTC clusters were classified into Loose, Tight and very Tight based on the median gray values obtained from DAPI staining on ImageJ software. Clinical data was collected from patient records and subjected to analysis using Descriptive statistics. Results: From the 50 patients included in the study, 22 (44%) patients exhibited tight clusters in central blood, while only 13 (26%) patients exhibited tight clusters in peripheral blood. A higher clinical stage was observed in a greater percentage of patients with tight clusters in central blood (early: 45.5% versus late: 54.5%), but the same findings could not be inferred with pathological staging (early stage: 59.1% versus late stage: 40.1%). No significant correlation with adverse pathological features was noted. Conclusions: This observational study provides an insight into the varying biological behaviours of similarly grouped cancers, which is based on the standard TNM staging. The study forms the basis for the hypothesis of tight clusters in the central and peripheral circulation, correlating with loco-regional and distant metastasis respectively, thus leading to poorer disease-free and overall survival rates.


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