scholarly journals Downregulation of CCL22 and mutated NOTCH1 in tongue and mouth floor squamous cell carcinoma results in decreased Th2 cell recruitment and expression, predicting poor clinical outcome

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuejie Li ◽  
Zheqi Liu ◽  
Wenkai Zhou ◽  
Xiaofang Liu ◽  
Wei Cao
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Early Stage ◽  
Clinical Stage ◽  
Th2 Cells ◽  
Advanced Stage ◽  
Cell Recruitment ◽  
Th2 Cell ◽  
Stage Disease

Abstract Objective Tongue and mouth floor squamous cell carcinoma (T/MF SCC) exhibits a high rate of local recurrence and cervical lymph node metastasis. The effect of the tumor microenvironment on T/MF SCC remains unclear. Materials and methods Transcriptome and somatic mutation data of patients with T/MF SCC were obtained from HNSC projects of the Cancer Genome Atlas. Immune infiltration quantification in early- (clinical stage I–II) and advanced-stage (clinical stage III–IV) T/MF SCC was performed using single sample Gene Set Enrichment Analysis and MCPcounter. Differentially expressed gene data were filtered, and their function was assessed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Kaplan–Meier survival curve analysis and Cox regression model were conducted to evaluate the survival of patients with the CCL22 signature. Maftools was used to present the overview of somatic mutations. Results In T/MF SCC, T helper (Th)2 cell counts were significantly increased in patients with early-stage disease compared to those with advanced-stage disease. Expression of the Th2 cell-related chemokine, CCL22, was downregulated in patients with advanced-stage T/MF SCC. Univariate and multivariate Cox analyses revealed that CCL22 was a good prognostic factor in T/MF SCC. A nomogram based on the expression of CCL22 was constructed to serve as a prognostic indicator for T/MF SCC. NOTCH1 mutations were found at a higher rate in patients with advanced-stage T/MF SCC than in those with early-stage T/MF SCC, resulting in the inhibition of the activation of the NOTCH1-Th2 cell differentiation pathway. The expression levels of CCL22, GATA-3, and IL4 were higher in patients with early-stage T/MF SCC than in those with advanced-stage T/MF SCC. Conclusion In T/MF SCC, high expression of CCL22 may promote the recruitment of Th2 cells and help predict a better survival. Mutations in NOTCH1 inhibit the differentiation of Th2 cells, facilitating tumor progression through a decrease in Th2 cell recruitment and differentiation.

scholarly journals Downregulation of CCL22 and Mutation of NOTCH1 in Tongue Squamous Cell Carcinoma Decreases Th2 Cell Recruitment and Expression to Predict Poor Clinical Outcomes

2021 ◽  
Author(s):  
Xuejie Li ◽  
Zheqi Liu ◽  
Wenkai Zhou ◽  
Wei Cao ◽  
Xiaofang Liu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Early Stage ◽  
Tongue Squamous Cell Carcinoma ◽  
Gene Set Enrichment Analysis ◽  
Th2 Cells ◽  
Advanced Stage ◽  
Cell Recruitment ◽  
Th2 Cell

Abstract Background: Tongue squamous cell carcinoma (TSCC) exhibits a high rate of local recurrence and cervical lymph node metastasis. The effect of the tumor microenvironment on TSCC remains unclear.Methods: Transcriptome data and somatic mutation data of TSCC were obtained from the HNSC project of The Cancer Genome Atlas (TCGA). Immune filtration analysis between early stage (clinical stage I–II) and advanced stage (III–IV) was performed using single-sample Gene Set Enrichment Analysis and MCPcounter. Differentially expressed genes were filtered and their related functions were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Kaplan-Meier survival analysis and a Cox-regression model were used to evaluate the survival of patients with the CCL22 signature. Maftools was used to show an overview of somatic mutations in TSCC. Results: In patients with TSCC, Th2 cells were significantly increased in patients in the early stage of the disease. The Th2 cell-related chemokine CCL22 was downregulated in patients in the advanced stage. Univariate and multivariate Cox analyses revealed CCL22 as a good prognostic factor for TSCC. A nomogram based on the expression of CCL22 was constructed as a prognostic indicator for TSCC. NOTCH1 mutation was increased in patients in the advanced stage, which inhibited activation of the NOTCH1-Th2 differentiation pathway.Conclusions: In TSCC, high expression of CCL22 can promote the recruitment of Th2 cells and predict better survival. Mutation of NOTCH1 inhibits the differentiation of Th2 cells. Combined with decreased Th2 cell recruitment and differentiation, tumor progression may occur.

scholarly journals Hypoxia-Inducible Factor-1α Expression in Indonesian Laryngeal Squamous Cell Carcinoma Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Agus Surono ◽  
Priyanto Priyanto ◽  
Sagung Rai Indrasari
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Early Stage ◽  
Clinical Stage ◽  
Hypoxia Inducible Factor ◽  
Advanced Stage ◽  
Chi Square ◽  
Chi Square Test

Objectives. This research aimed to determine the association between hypoxia-inducible factor-1α (HIF-1α) expression and laryngeal squamous cell carcinoma clinical stage. Methods. We retrospectively analyzed paraffin-embedded tissue from 47 laryngeal squamous cell carcinoma (LSCC) patients from 2011 to 2014. HIF-1α expression was analyzed by immunohistochemistry using an anti-HIF-1α mouse monoclonal antibody. The association between HIF-1α expression and clinical stage was analyzed using the chi square test. Results. The glottis was the predominant site of laryngeal squamous cell carcinoma occurrence, and 43/47 (91.5%) patients presented at an advanced stage. Of the advanced stage patients, 27/43 stained positive for HIF-1α expression and 16/43 stained negative. Of the early stage patients, 2/4 stained positive for HIF-1α expression and 2/4 stained negative. Statistical analysis did not demonstrate significant association of HIF-1α expression. Conclusion. There was no statistically significant association between HIF-1α expression and the clinical stage or histological differentiation of LSCC.

Association between central and peripheral circulating tumor cell (CTC) clusters in oral squamous cell carcinoma (OSCC): A prospective, observational study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15548-e15548
Author(s):  
Ritvi K Bagadia ◽  
Vishal Uchila Shishir Rao ◽  
Ajay Balakrishnan ◽  
Abhijith George ◽  
Prashant Kumar
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Observational Study ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Early Stage ◽  
Clinical Stage ◽  
Survival Rates ◽  
Tnm Staging ◽  
Dapi Staining

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.

scholarly journals Adjunctive Therapy in Oral Cancer

2021 ◽  
pp. 1903-1913
Author(s):  
Amit Dhawan
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Patients ◽  
Squamous Cell ◽  
Adjunctive Therapy ◽  
Early Stage ◽  
Advanced Stage ◽  
Oral Cancer Patients

AbstractOral squamous cell carcinoma is the third most common cancer in Indian subcontinent affecting people with lower socioeconomic status. Due to inadequate screening facilities and lack of awareness among individuals most of the oral cancer cases are detected at an advanced stage. As early stage oral squamous cell carcinoma patients can be treated with single modality treatment (surgery or radical radiotherapy), multimodality regimen (surgery followed by concurrent chemoradiation) is adopted for high risk advanced stage cancers with multiple adverse features like extra nodal extension, lymphovascular invasion and perineural spread. The chapter outlines the principles of adjunctive therapy in oral cancer patients with special reference to different techniques, indications of radiotherapy and role of chemotherapeutic regimes in improving the overall survival of advanced stage oral cancer patients.

scholarly journals To evaluate disparity between clinical and pathological tumor-node-metastasis staging in oral cavity squamous cell carcinoma patients and its impact on overall survival: An institutional study

2015 ◽  
Vol 04 (04) ◽  
pp. 183-185 ◽  
Author(s):  
Karan Gupta ◽  
Naresh K Panda ◽  
Jaimanti Bakshi ◽  
Ashim Das
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Early Stage ◽  
Tnm Staging ◽  
Advanced Stage ◽  
Tumor Node Metastasis ◽  
Node Metastasis ◽  
N Stage

Abstract Background: Accurate clinical staging is important for patient counseling, treatment planning, prognostication, and rational design of clinical trials. In head and neck squamous cell carcinoma, discrepancy between clinical and pathological staging has been reported. Objective: To evaluate any disparity between clinical and pathological tumor-node-metastasis (TNM) staging in oral cavity squamous cell carcinoma (OCSCC) patients and any impact of the same on survival. Materials and Methods: Retrospective chart review from year 2007 to 2013, at a tertiary care center. Statistical Analysis: All survival analyses were performed using SPSS for Windows version 15 (Chicago, IL, USA). Disease-free survival curves were generated using Kaplan-Meier algorithm. Results: One hundred and twenty-seven patients with OCSCC were analyzed. Seventy-nine (62.2%) were males and 48 (37.8%) females with a mean age at presentation 43.6 years (29-79 years). The highest congruence between clinical and pathological T-staging seen for clinical stage T1 and T4 at 76.9% and 73.4% with pathological T-stage. Similarly, the highest congruence between clinical and pathological N-stage seen for clinical N0 and N3 at 86.4% and 91.7% with pathological N-stage. Of clinically early stage patients, 67.5% remained early stage, and 32.5% were upstaged to advanced stage following pathological analysis. Of the clinically advanced stage patients, 75% remained advanced, and 25% were pathologically downstaged. This staging discrepancy did not significantly alter the survival. Conclusion: Some disparity exists in clinical and pathological TNM staging of OCSCC, which could affect treatment planning and survival of patients. Hence, more unified and even system of staging for the disease is required for proper decision-making.

Demographics and incidence of anal squamous cell carcinoma in people living in high HIV prevalence geographical areas

2021 ◽  
pp. sextrans-2021-055271
Author(s):  
Danielle Rebecca Louise Brogden ◽  
Christos Kontovounisios ◽  
Sundhiya Mandalia ◽  
Paris Tekkis ◽  
Sarah Catherine Mills
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Early Stage ◽  
Incidence Rates ◽  
Hiv Prevalence ◽  
People Living With Hiv ◽  
Early Stage Disease ◽  
Anal Squamous Cell Carcinoma ◽  
Stage Disease

ObjectivesAnal squamous cell carcinoma (ASCC) is an uncommon cancer that is rapidly increasing in incidence. HIV is a risk factor in the development of ASCC, and it is thought that the rapidly increasing incidence in men is related to increasing numbers of people living with HIV (PLWH). We undertook a population-based study comparing the demographics and incidence of ASCC in patients residing high HIV prevalence areas in England to patients living in average HIV prevalence areas in England.MethodsThis is a cross-sectional study following the ‘Strengthening the Reporting of Observational Studies in Epidemiology’ statement. Demographic data and incidence rates of ASCC within Clinical Commissioning Groups (CCGs) between 2013 and 2018 were extracted from the Cancer Outcomes and Services Dataset. CCGs were then stratified by HIV prevalence from data given by Public Health England, and high HIV prevalence geographical areas were compared with average HIV geographical areas.ResultsPatients in high HIV areas were more likely to be young and male with higher levels of social deprivation. Incidence rates in men between 2013 and 2017 were higher in high HIV areas than average HIV areas with a rapidly increasing incidence rates in early-stage disease and a 79.1% reduction in incidence of metastatic stage 4 disease.Whereas women in high HIV areas had lower ASCC incidence than the national average and a low incidence of early-stage disease; however, metastatic disease in women had quintupled in incidence in high HIV areas since 2013.ConclusionsPatients presenting with ASCC in high HIV geographical areas have different demographics to patients presenting in average HIV geographical areas. This may be related to screening programmes for PLWH in high HIV areas.

Stat3 Expression in Oral Squamous Cell Carcinoma: Association with Clinicopathological Parameters and Survival

2006 ◽  
Vol 21 (3) ◽  
pp. 175-183 ◽  
Author(s):  
N.G. Shah ◽  
T.I. Trivedi ◽  
R.A. Tankshali ◽  
J.A. Goswami ◽  
D.H. Jetly ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Early Stage ◽  
Disease Stage ◽  
Clinicopathological Parameters ◽  
Early Event ◽  
Advanced Stage ◽  
Intense Staining

The present study sought to explore the occurrence of signal transducer and activator of transcription 3 (Stat3) in patients with oral squamous cell carcinoma (n=135) and its potential relationship with clinicopathological parameters and survival. Stat3 expression was studied by immunohistochemistry. Cytoplasmic or nuclear localization of Stat3 was observed in 62% of patients, whereas only nuclear Stat3 expression was found in 44%. Stat3 positivity in early-stage patients was 45% compared to 79% in advanced-stage patients. However, early-stage Stat3-positive patients showed a gradual increase in staining intensity, with intense staining seen in 52% of the tumors compared to 18% in Stat3-positive advanced-stage patients, where a gradual decrease in intensity expression was observed (p=0.001). Stat3 showed a significant positive correlation with disease stage (p=0.001), nodal status (p=0.033) and tumor size (p=0.001). Multivariate survival analysis using the Cox proportional hazard regression model showed that nuclear Stat3 was a significant independent prognosticator for both relapse-free survival (p=0.014) and overall survival (p=0.042) in early-stage patients. Our results indicated that Stat3 activation is an early event in oral squamous cell carcinoma and represents a potential risk factor for poor prognosis in early-stage patients.

Correlation of CTCs with disease progression in Indian oral cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15541-e15541
Author(s):  
Jayant Khandare ◽  
Burhanuddin Qayyumi ◽  
Atul Bharde ◽  
Gourishankar Aland ◽  
Sreeja Jayant ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Early Stage ◽  
Clinicopathological Parameters ◽  
Depth Of Invasion ◽  
Advanced Stage ◽  
Pathological Features ◽  
Positive Correlation

e15541 Background: Head and neck squamous cell carcinoma is leading cancer in the India with Oral squamous cell carcinoma (OSCC) as the most frequent subtype. OSCC is classified as a locoregional disease and its increased frequency is attributed to lack of good biomarkers compared to other epithelial cancers. At the time of diagnosis, above 50% of cases present the manifestation of advanced-stage disease, and are predisposed to disease failure in spite of appropriate treatment. Thus, early diagnosis of OSCC can significantly reduce the disease burden. Here we describe regulatory approved method to establish Circulating tumor cells (CTCs) presence in OSCC Indian patients and its positive correlation with various clinicopathological parameters, suggesting the potential use of CTCs as a significant parameter to stratify oral cancer with respect to the disease advancement. Methods: In a cross-sectional observational study, 230 OSCC patients at the different pathological stage of the disease and treatment mode were enrolled. CTCs were isolated using approved OncoDiscover liquid biopsy technology (Drug controller general of India approved), platform technology based on immunomagnetic CTC enumeration. CTCs were detected for CK18 presence and well-defined, DAPI-stained nuclei. Enumerated CTC subsequently analyzed for various clinic-pathological parameters such as pstage, extra-capsular spread (ECS), lymphovascular emboli (LVE), perineural invasion (PNI) and depth of invasion (DOI). CTC cut off values were obtained to differentiate early vs advanced stages with respect to different clinical stages and parameters. Results: CTCs of OSCC patients correlated positively with the cancer stages (clinical as well as pathological) as well as aggressive pathological features. The presence of aggressive pathological features that often suggest the poor outcome of the disease, we observed a 25-50 % increase in CTC number. Early stage, treatment naïve patients had lower number of CTCs. Mean CTC number in advanced-stage patients was 50 % higher than early-stage OSCC patients. Conclusions: Considering a positive correlation of CTC number with various pathophysiological features, CTC can be contemplated as a reliable parameter to predict the disease outcome in oral cancer. The consistent presence of CTC across all disease stages also suggests a probable nature of OSCC as a biological systematic disease. Clinical trial information: CTRI/2018/03/012905.

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