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

Author(s):  
Xuejie Li ◽  
Zheqi Liu ◽  
Wenkai Zhou ◽  
Wei Cao ◽  
Xiaofang Liu

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.

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuejie Li ◽  
Zheqi Liu ◽  
Wenkai Zhou ◽  
Xiaofang Liu ◽  
Wei Cao

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.


Author(s):  
Amit Dhawan

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.


2015 ◽  
Vol 04 (04) ◽  
pp. 183-185 ◽  
Author(s):  
Karan Gupta ◽  
Naresh K Panda ◽  
Jaimanti Bakshi ◽  
Ashim Das

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.


Head & Neck ◽  
2016 ◽  
Vol 39 (1) ◽  
pp. 147-150 ◽  
Author(s):  
Orna Katz ◽  
Yuval Nachalon ◽  
Ohad Hilly ◽  
Thomas Shpitzer ◽  
Gideon Bachar ◽  
...  

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