High PD-L1 Expression Correlates with Metastasis and Poor Prognosis in Oral Squamous Cell Carcinoma.
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ABSTRACT:
SUBMITTER: Lin YM
PROVIDER: S-EPMC4642967 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesOral cancer is the ninth most common cancer worldwide and a leading cause of cancer-related death. Oral squamous cell carcinoma (OSCC) accounts for 90% of all oral cancers. Autophagy is a conserved essential catabolic process related to OSCC. The aim of this study was to elucidate diagnostic and prognostic autophagy-related biomarkers in OSCC.MethodsThe OSCC gene expression data set was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between the OSCC samples and adjacent healthy tissues were identified by R software. The Human Autophagy Database was screened, which revealed 222 autophagy-related genes. The autophagy-related DEGs were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were applied. Protein-protein interaction network analysis was performed in the STRING database. cytoHubba in the Cytoscape software was applied to determine the top 10 hub genes. The data set of patients with OSCC from The Cancer Genome Atlas (TCGA) was used to evaluate the prognostic value of the 10 hub genes. The association between prognosis-related hub genes and immune infiltrates was explored.ResultsTwenty-seven autophagy-related DEGs were identified. The top 10 hub genes were CCL2, CDKN2A, CTSB, CTSD, CXCR4, ITGA6, MAP1LC3A, MAPK3, PARP1, and RAB11A. ITGA6 was identified as the most efficient biomarker. Receiver operating characteristic curve analysis indicated that ITGA6 had the highest diagnostic accuracy for OSCC (area under the curve = 0.925). ITGA6 expression was significantly related to immune infiltrates.ConclusionsThe autophagy-related gene ITGA6 might be an efficient diagnostic and prognostic biomarker in OSCC.
| S-EPMC10023534 | biostudies-literature
Project description:BackgroundPTPRF interacting protein alpha 1 (PPFIA1) is reportedly related to the occurrence and progression of several kinds of malignancies. However, its role in esophageal squamous cell carcinoma (ESCC) is unclear. This current study investigated the prognostic significance and biological functions of PPFIA1 in ESCC.MethodsOncomine, Gene Expression Profiling Interactive Analysis (GEPIA), and Gene Expression Omnibus (GEO) were used to investigate PPFIA1 expression in esophageal cancer. The relationship between PPFIA1 expression and clinicopathological characteristics and patient survival was evaluated in GSE53625 dataset, and verified in the cDNA array based on qRT-PCR and tissue microarray (TMA) dataset based on immunohistochemistry. The impact of PPFIA1 on the migration and invasion of cancer cells were investigated by wound-healing and transwell assays, respectively.ResultsThe expression of PPFIA1 was obviously increased in ESCC tissues versus adjacent esophageal tissues according to online database analyses (all P < 0.05). High PPFIA1 expression was closely related to several clinicopathological characteristics, including tumor location, histological grade, tumor invasion depth, lymph node metastasis, and tumor-node-metastasis (TNM) stage. High PPFIA1 expression was related to worse outcomes and was identified as an independent prognostic factor of overall survival in ESCC patients (GSE53625 dataset, P = 0.019; cDNA array dataset, P < 0.001; TMA dataset, P = 0.039). Downregulation of PPFIA1 expression can significantly reduce the migration and invasion ability of ESCC cells.ConclusionPPFIA1 is related to the migration and invasion of ESCC cells, and can be used as a potential biomarker to evaluate the prognosis of ESCC patients.
| S-EPMC10169376 | biostudies-literature
Project description:MicroRNAs (miRNAs) in oral squamous cell carcinoma (OSCC)-derived small extracellular vesicles (sEVs) play a pivotal role in modulating intercellular communications between tumor cells and other cells in microenvironment, thereby influencing tumor progression and the efficacy of therapeutic interventions. However, a comprehensive inventory of these secretory miRNAs in sEVs and their biological and clinical implications remains elusive. This study aims to profile the miRNA content of OSCC cell lines sEVs and computationally elucidate their biological and clinical relevance. We conducted miRNA sequencing to compare the miRNA profiles of OSCC cells and their corresponding sEVs. Our motif enrichment analysis identified specific sorting motifs that are implicated in either cellular retention or preferential sEVs secretion. Target cell analysis suggested that the sEVs miRNAs potentially interact with various immune cell types, including natural killer cells and dendritic cells. Additionally, we explored the clinical relevance of these miRNAs by correlating their expression levels with TNM stages and patient survival outcomes. Intriguingly, our findings revealed that a distinct sEVs miRNA signature is associated with lymph node metastasis and poorer survival in patients in TCGA-HNSC dataset. Collectively, this research furthers our understanding of the miRNA sorting mechanisms in OSCC and underscores their clinical implications.
2024-02-07 | GSE254937 | GEO
Project description:The association between the hypoxia-inducible gene termed regulated in development and DNA damage responses 1 (REDD1) and microvessel density (MVD) in human oral cancer has rarely been reported. The present study aimed to explore REDD1 expression in oral squamous cell carcinoma (OSCC), its clinical prognostic significance and its correlation with angiogenesis. REDD1 expression in 23 pairs of fresh-frozen OSCC and matched peritumoral mucosal tissues was quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Furthermore, 74 formalin-fixed paraffin-embedded OSCC tissues were collected to detect REDD1 expression and CD34-positive MVD by immunohistochemistry (IHC). The association between REDD1 expression and MVD, patients' clinicopathological characteristics and cancer-associated survival rate was also evaluated using the log-rank (Mantel-Cox) test. The results from RT-qPCR and western blotting demonstrated that REDD1 expression was significantly higher in OSCC tissues compared with peritumoral mucosal tissues (P<0.05). In addition, the results from IHC revealed that REDD1 expression was higher in OSCC tissues compared with peritumoral tissues. Furthermore, REDD1 expression was associated with advanced clinical stage, poorer tumor differentiation, lymphatic metastasis and tumor recurrence (P=0.000, P=0.003, P=0.006 and P<0.001, respectively). Additionally, REDD1 overexpression was positively correlated with MVD (r=0.7316; P<0.001). The results from Kaplan-Meier survival analysis demonstrated a significantly reduced disease-free survival and overall survival in patients with OSCC and high REDD1 expression (P<0.001). REDD1 may therefore serve as a novel prognostic biomarker, a key regulatory checkpoint that could coordinate angiogenesis and a new therapeutic target for patients with OSCC.
| S-EPMC6923876 | biostudies-literature
Project description:Objective Pleomorphic carcinoma (PC) is a rare pulmonary epithelial malignant tumor with a poor prognosis. The objective of the present study was to investigate the programmed death-ligand 1 (PD-L1) expression in PC and its correlation between the clinicopathological factors and prognosis. Methods Clinical and pathological data of 35 patients with surgically resected PC encountered from 2002 to 2016 at our institution were collected. The PD-L1 expression on tumor cells was evaluated via immunohistochemistry (clone 22C3). We examined the correlation between the PD-L1 expression and patients' clinicopathological factors and their prognosis. Results A high PD-L1 expression (≥50%) was seen in 21 (60%) patients, and parietal-pleural invasion was significantly correlated with a high PD-L1 expression (p=0.012). The 5-year overall survival and relapse-free survival were 68.2% and 43.2%, respectively. Tumor size ≥50 mm (p=0.021), lymph node metastasis (p=0.023), and a high PD-L1 expression (p=0.047) were correlated with a short relapse-free survival. Since lymph node metastasis was an independent risk factor of a poor overall survival (p=0.012), patients with a high PD-L1 expression also tended to have a worse overall survival than those with low levels (p=0.081). Conclusion A high PD-L1 expression is frequently seen in PC. The PD-L1 expression is associated with parietal-pleural invasion and might indicate a poor prognosis.
| S-EPMC6478980 | biostudies-literature
Project description:Oral squamous cell carcinoma (OSCC) is a common public health problem worldwide with poor prognosis, which is largely due to lymph node metastasis and recurrence. Identification of specific molecular markers of OSCC with lymph node metastasis would be very important for early and specific diagnosis. In this study, we screened for the potential prognosis markers via unbiased transcriptomic microarray analysis in paired two OSCC cell lines, a lymph node metastatic HN12 cell line and a low metastatic parental HN4 cell line. The results showed that vimentin, with 87-fold increase of expression, was on the top of all upregulated genes in metastatic HN12 cells compared to non-metastatic HN4 cells. Treatment of non-metastatic HN4 cells with TGF-β1 induced epithelial to mesenchymal transition (EMT), with increased vimentin expression as well as enhanced migration activity. Consistently, knockdown of vimentin via siRNA resulted in suppressed invasion and migration activities of HN12 cells, suggesting an essential role of vimentin in EMT-related functions of OSCC cells. Finally, immunohistochemical (IHC) staining analysis showed that high vimentin expression was strongly associated with high lymph node metastases (p < 0.05), and poor overall survival (p < 0.05) in OSCC patients. Thus, high vimentin expression is strongly associated with increased metastatic potential, and may serve as a prediction marker for poor prognosis in OSCC patients.
| S-EPMC5155220 | biostudies-literature
Project description:BackgroundWhether the expression of Golgi phosphoprotein 3 (GOLPH3) correlates with esophageal cancer tumorigenesis is currently unclear. The aim of this study was to examine GOLPH3 expression in patients with esophageal squamous cell cancer (ESCC) and explore its clinical significance.MethodsDifferences in the expression of GOLPH3 at the mRNA and protein level were examined via quantitative reverse transcriptase PCR and western blotting, respectively. GOLPH3 expression levels in ESCC tissue were determined through immunohistochemistry, and were compared in accordance with specific clinicopathological features of the patients and tissue specimens. Factors associated with patient survival were also analyzed.ResultsA notably higher level of GOLPH3 expression was found in ESCC cell lines and tissues at both mRNA and protein levels. High expression of GOLPH3 in ESCC patients was positively associated with clinical stage, TNM classification, histological differentiation and vital status (all P<0.0001). Expression of GOLPH3 was found to be an independent prognostic factor in ESCC patients. ESCC patients expressing high levels of GOLPH3 exhibited a substantially lower 5-year overall survival than GOLPH3-negative patients. Furthermore, a significant correlation between high GOLPH3 expression and shorter overall survival time was found in different subgroups of ESCC patients stratified by the clinical stage, T classification, and lymph node metastasis.ConclusionsExperiments demonstrated potential involvement of GOLPH3 in the development, differentiation, and tumorigenesis of ESCC, and concludes the possibility of its use as a diagnostic and prognostic marker in patients with ESCC.
| S-EPMC3462781 | biostudies-literature
Project description:To analyze the expression of the transforming acidic coiled-coil protein 3 (TACC3) in esophageal squamous cell carcinoma (ESCC) samples, and to identify whether TACC3 can serve as a biomarker for the diagnosis and prognosis of ESCC, qPCR, western blotting and immunohistochemistry staining (IHC) were utilized to detect the expression of TACC3. Furthermore, cell growth, colony formation, migration ability and the epithelial-mesenchymal transition markers of ESCC cells in which TACC3 were knocked-down were measured. The mRNA and protein levels of TACC3 were higher in ESCC specimens compared to non-tumorous esophageal epithelial tissues. IHC results revealed TACC3 expression was significantly correlated to differentiation (p = 0.017) and lymphoid nodal status (p = 0.028). The patients with high-expression of TACC3 had a significantly poor prognosis compared to those of low-expression (p = 0.017), especially in the patients at stages I-II (p = 0.028). Multivariate analysis indicated that TACC3 expression was an independent prognostic factor for ESCC patients (p = 0.025). Knockdown of TACC3 inhibited the ability of cell proliferation, colony formation and migration. This study first identifies TACC3 not only as a useful biomarker for diagnose and prognosis of ESCC, but also as a potential therapeutic target for patients with ESCC.
| S-EPMC4466654 | biostudies-literature
Project description:BACKGROUND:Lymph node metastasis (LNM) is a major determinant of prognosis and treatment planning of oral squamous cell carcinoma (OSCC). Cysteine cathepsins constitute a family of proteolytic enzymes with known role in the degradation of the extracellular matrix. Involvement in pathological processes, such as inflammation and cancer progression, has been proved. The aim of the study was to discover the clinicopathological and prognostic implications of cathepsin K (CTSK) expression in oral squamous cell carcinoma. METHODS:Eighty-three patients with primary OSCC, treated surgically between 1996 and 2000, were included. Gene expression data were acquired from a previously reported study. Human papilloma virus (HPV) status was previously determined by an algorithm for HPV-16. CTSK Protein expression was semi-quantitatively determined by immunohistochemistry in tumor and stromal cells. Expression data were correlated with various clinicopathological variables. RESULTS:Elevated gene and protein expression of CTSK were strongly associated to LNM and perineural invasion (p?<?0.01). Logistic regression analysis highlighted increased CTSK protein expression in tumor cells as the most significant independent factor of lymphatic metastasis (OR?=?7.65, CI:2.31-23.31, p?=?0.001). Survival analysis demonstrated CTSK protein expression in both stromal and tumor cells as significant indicators of poor 5-year disease specific survival (HR?=?2.40, CI:1.05-5.50, p?=?0.038 for stromal cells; HR?=?2.79, CI:1.02-7.64, p?=?0.045 for tumor cells). CONCLUSION:Upregulation of CTSK seems to be associated with high incidence of lymphatic spread and poor survival in OSCC. CTSK could therefore serve as a predictive biomarker for OSCC.
| S-EPMC5885370 | biostudies-literature
Project description:Despite its rare incidence worldwide, penile squamous cell carcinoma (PeSCC) still presents with significant morbidity and mortality due to the limited treatment options for advanced patients, especially those in developing countries. The program death-1 (PD-1)/PD-1 ligand (PD-L1) axis has been demonstrated to play an important role in tumor immune escape, and immunotherapies targeting this pathway have shown great success in certain cancer types. Here, we analyzed the expression pattern of PD-L1 in tumor cells and tumor-infiltrating lymphocytes (TILs) in PeSCC with a multi-center cohort. We found that the majority of PeSCCs (53.4%) were PD-L1-positive and that high PD-L1 expression in tumor cells was associated with a poor prognosis. Notably, PD-L1 expression in tumor cells was significantly associated with the extent of TILs and CD8+ TILs. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) showed that PD-L1 was positively correlated with interferon-gamma (IFNγ) and CD8+ gene expression. Moreover, we defined the constitutive and inducible surface expression of PD-L1 in newly established primary PeSCC cell lines. Interestingly, two PeSCC cell lines had high intrinsic PD-L1 expression. Another cell line showed low PD-L1 expression, but the PD-L1 expression could be induced by IFNγ stimulation. Overall, our data showed that high PD-L1 expression in penile tumor cells indicated a poor prognosis. The upregulation of PD-L1 in PeSCC included both extrinsic and intrinsic mechanisms. These findings indicated that the PD-1/PD-L1 axis might be a potential therapeutic target for patients with penile squamous cell carcinoma.
| S-EPMC5353932 | biostudies-literature