scholarly journals PDL-1 expression in oral squamous cell carcinoma and implications for treatment.

2019 ◽  
Vol 5 (suppl) ◽  
pp. 82-82
Author(s):  
Vijay Kumar Srinivasalu ◽  
Narayana Subramaniam ◽  
Subramania Iyer ◽  
Ajit Nambiar ◽  
Manzoor Koyakutty ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Significance ◽  
Tumour Microenvironment ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Expression Levels ◽  
Key Factor

82 Background: PDL-1 expression has been shown in multiple tumours to be a key factor in treatment response and immunogenicity. In oral squamous cell carcinoma (OSCC), its role is controversial; the expression levels, prognostic significance and therapeutic relevance are unclear. This study was performed to determine the incidence of PDL-1 expression in OSCC, and to determine its correlation with demographic, clinical and pathological features, recurrence and survival. Methods: PDL1 expression levels were determined by immunohistochemistry (DAKO kit) on 64 samples of OSCC obtained during resection on tumour (T) and tumour infiltrating lymphocytes (TILs). Statistical analysis was performed for corelation with clinicopathological features and survival. We also analysed PD1/PDL1 expression on the mRNA-seq data from The Cancer Genome Atlas (TCGA) (n = 527) and Gene Expression Omnibus (GEO) (n = 61) for validation. Results: PDL1 expression of < 1% was the most common for T (92%) and TILs (56%). Tumour PDL-1 expression < 1% had higher lymphovascular invasion (LVI) (p = 0.044) and bone invasion (p = 0.010). TIL PDL-1 expression < 1% was more common in patients < 45 years (p = 0.023) with more local recurrences (p = 0.020). For TCGA data, overall survival (OS) in the young ( < 45 years) was reduced in patients with low ( < 1%) PD1 expression (p = 0.010) while GEO data showed that older patients ( > 45 years) had a significantly higher PD1 expression level (p = 0.044). Conclusions: PDL1 expression in OSCC was low. Low TIL PDL1 expression was more common in patients with age < 45 years, with a higher chance of local recurrence. Genomic data also validated a potential link between PD1 expression and age. On the tumour, PD1 expression may be an important prognosticator, while on TILs, PDL1 is likely more relevant. Moreover PDL1 expression on the tumour is likely to be heterogeneous, so TIL PDL1 expression may be more representative of the tumour microenvironment and a better prognostic marker.

PDL-1 expression in oral squamous cell carcinoma and implications for treatment.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17527-e17527
Author(s):  
Vijay Kumar Srinivasalu ◽  
Narayana Subramaniam ◽  
Subramania Iyer ◽  
Ajit Nambiar ◽  
Manzoor Koyakutty ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Local Recurrence ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Significance ◽  
Final Analysis ◽  
The Cancer Genome Atlas ◽  
Curative Intent ◽  
Expression Levels

e17527 Background: PDL-1 expression has been shown in multiple tumours to be a key factor in treatment response and immunogenicity. In oral squamous cell carcinoma (OSCC), its role is controversial; the expression levels, prognostic significance and therapeutic relevance are unclear. This study was performed to determine the incidence of PDL-1 expression in OSCC, and to determine its correlation with demographic, clinical and pathological features, recurrence and survival. Methods: PDL-1 IHC (Dako kit) was determined on 64 samples of OSCC obtained during curative intent resection. PDL-1 expression levels were determined in tumour (T) and tumour infiltrating lymphocytes (TILs). Statistical analysis was performed. Results were validated on the mRNA-seq data from the Cancer Genome Atlas (TCGA) for head and neck squamous cell carcinoma (HNSCC). Results: 64 patients were included in the final analysis with a mean age of 54 years. < 1% expression was the most common for T (92%) and TILs (56%). Tumour PDL-1 expression < 1% had higher risk of lymphovascular invasion (LVI) (p = 0.044) and bone invasion (p = 0.010). TIL PDL-1 expression < 1% was more common in patients ≤45 years (p = 0.023) with higher chances of local recurrence (p = 0.020) and reduced local recurrence free survival (p = 0.047). For the TCGA data, low ( < 1%) PDL-1 expression was associated with a significant reduction in OS and DFS in the young (≤45 years) (p = 0.0078 and 0.0089 respectively), but not for older patients ( > 45 years) (p = 0.21 and 0.88 respectively). Conclusions: PDL-1 expression in OSCC was low. TIL PDL-1 expression < 1% was more common in those ≤45 years, and associated with a higher chance of local recurrence and poorer survival. The role of PDL-1 expression in prognosis of OSCC is controversial, with our data being the first to correlate low PDL-1 expression and poorer outcomes with younger patients. These results were validated by the TCGA data for HNSCC across multiple subsites. Further study is required to determine if this pathway plays a significant role in local control and survival.

scholarly journals JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chao Jing ◽  
Dandan Liu ◽  
Qingchuan Lai ◽  
Linqi Li ◽  
Mengqian Zhou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Gene Expression Omnibus ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
In Vivo Experiments

Abstract Background Deubiquitinating enzymes (DUBs) play critical roles in various cancers by modulating functional proteins post-translationally. Previous studies have demonstrated that DUB Josephin Domain Containing 1 (JOSD1) is implicated in tumor progression, however, the role and mechanism of JOSD1 in head and neck squamous cell carcinoma (HNSCC) remain to be explored. In this study, we aimed to identify the clinical significance and function of JOSD1 in HNSCC. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to find novel DUBs in HNSCC. Immunohistochemistry assay was performed to determine the expression of JOSD1 in our cohort of 42 patients suffered with HNSCC. Kaplan–Meier analysis was used to identify the correlation between JOSD1 and the prognosis of HNSCC patients. The regulation of BRD4 on JOSD1 was determined by using pharmacological inhibition and gene depletion. The in vitro and in vivo experiments were conducted to elucidate the role of JOSD1 in HNSCC. Results The results of IHC showed that JOSD1 was aberrantly expressed in HNSCC specimens, especially in the chemoresistant ones. The overexpression of JOSD1 indicated poor clinical outcome of HNSCC patients. Moreover, JOSD1 depletion dramatically impaired cell proliferation and colony formation, and promoted cisplatin-induced apoptosis of HNSCC cells in vitro. Additionally, JOSD1 suppression inhibited the tumor growth and improved chemosensitivity in vivo. The epigenetic regulator BRD4 contributed to the upregulation of JOSD1 in HNSCC. Conclusions These results demonstrate that JOSD1 functions as an oncogene in HNSCC progression, and provide a promising target for clinical diagnosis and therapy of HNSCC.

scholarly journals Salivary LDOC1 is a gender-difference biomarker of oral squamous cell carcinoma

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6732 ◽  
Author(s):  
Chung-Ji Liu ◽  
Jen-Hao Chen ◽  
Shih-Min Hsia ◽  
Chiu-Chu Liao ◽  
Hui-Wen Chang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Suppressor Gene ◽  
Clinicopathological Characteristics ◽  
Pcr Analysis ◽  
Expression Levels ◽  
Low Levels

Background The X-linked tumor suppressor gene LDOC1 is reported to be involved in oral cancer. The detection of biomarkers in salivary RNA is a non-invasive strategy for diagnosing many diseases. The aim of the present study was to investigate the potential of salivary LDOC1 as a biomarker of oral cancer. Methods We determined the expression levels of LDOC1 in the saliva of oral squamous cell carcinoma (OSCC) subjects, and investigated its correlation with various clinicopathological characteristics. The expression levels of salivary LDOC1 were detected in 53 OSCC subjects and 43 healthy controls using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. We used Fisher’s exact test to analyze the correlations between expression levels and clinicopathological characteristics. Results Salivary LDOC1 was significantly upregulated in females with OSCC (p = 0.0072), and significantly downregulated in males with OSCC (p = 0.0206). Eighty-nine percent of male OSCC subjects who smoked expressed low levels of LDOC1. OSCC cell lines derived from male OSCC subjects expressed low levels of LDOC1. Conclusions A high level of salivary LDOC1 expression is a biomarker of OSCC in females. A high percentage of male OSCC subjects who smoke express low levels of salivary LDOC1. A low level of salivary LDOC1 expression is a biomarker of OSCC in males.

scholarly journals Prognostic Significance of PD-L1 and mTOR Expression in Oral Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Nattinee Charoen ◽  
Kitti Jantharapattana ◽  
Paramee Thongsuksai
Keyword(s):  
Squamous Cell Carcinoma ◽  
Regression Analysis ◽  
Prognostic Factors ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cox Regression ◽  
Prognostic Significance ◽  
P Value ◽  
Cox Regression Analysis

Objective: Programmed cell death ligand 1 (PD-L1) and mammalian target of rapamycin (mTOR) are key players in host immune evasion and oncogenic activation, respectively. Evidence of the prognostic role in oral squamous cell carcinoma (OSCC) is conflicting. This study examined the associations of PD-L1 and mTOR expression with 5-year overall survival in OSCC patients. Material and Methods: The expressions of PD-L1 and mTOR proteins were immunohistochemically evaluated on tissue microarrays of 191 patients with OSCC who were treated by surgery at Songklanagarind Hospital, Thailand from 2008 to 2011. Cox regression analysis was used to determine independent prognostic factors. Results: PD-L1 expression was observed in 14.1% of cases while mTOR expression was present in 74.3% of cases. Females were more likely to have tumors with PD-L1 (p-value=0.007) and mTOR expressions (p-value=0.003) than males. In addition, lower clinical stage and well differentiated tumor are more likely to have mTOR expression (p-value= 0.038 and p-value<0.001, respectively). Cox regression analysis showed that age, tumor stage, nodal stage, combined surgical treatment with radiation or chemoradiation therapy, surgical margin status, PD-L1 expression and mTOR expression are independent prognostic factors. High PD-L1 expression (hazard ratio (HR) 3.14, 95% confidence interval (CI), 1.26–7.79) and high mTOR expression (HR 1.69, 95% CI, 1.00–2.84) are strong predictors of poor outcome. Conclusion: A proportion of OSCC expressed PD-L1 and mTOR proteins. Expression of PD-L1 and mTOR proteins are strong prognostic factors of OSCC.

Prognostic significance of molecular markers in oral squamous cell carcinoma: A multivariate analysis

Head & Neck ◽  
2009 ◽  
Vol 31 (12) ◽  
pp. 1544-1556 ◽  
Author(s):  
Neelam G. Shah ◽  
Trupti I. Trivedi ◽  
Rajen A. Tankshali ◽  
Jignesh V. Goswami ◽  
Dhaval H. Jetly ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Multivariate Analysis ◽  
Molecular Markers ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Significance

Prognostic significance of beta-2 adrenergic receptor in oral squamous cell carcinoma

2012 ◽  
Vol 10 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Diego Mauricio Bravo-Calderón ◽  
Denise Tostes Oliveira ◽  
Aparecido Nilceu Marana ◽  
Suely Nonogaki ◽  
André Lopes Carvalho ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Adrenergic Receptor ◽  
Prognostic Significance ◽  
Beta 2
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