Transcriptomic dissection of tongue squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>The head and neck/oral squamous cell carcinoma (HNOSCC) is a diverse group of cancers, which develop from many different anatomic sites and are associated with different risk factors and genetic characteristics. The oral tongue squamous cell carcinoma (OTSCC) is one of the most common types of HNOSCC. It is significantly more aggressive than other forms of HNOSCC, in terms of local invasion and spread. In this study, we aim to identify specific transcriptomic signatures that associated with OTSCC.</p> <p>Results</p> <p>Genome-wide transcriptomic profiles were obtained for 53 primary OTSCCs and 22 matching normal tissues. Genes that exhibit statistically significant differences in expression between OTSCCs and normal were identified. These include up-regulated genes (MMP1, MMP10, MMP3, MMP12, PTHLH, INHBA, LAMC2, IL8, KRT17, COL1A2, IFI6, ISG15, PLAU, GREM1, MMP9, IFI44, CXCL1), and down-regulated genes (KRT4, MAL, CRNN, SCEL, CRISP3, SPINK5, CLCA4, ADH1B, P11, TGM3, RHCG, PPP1R3C, CEACAM7, HPGD, CFD, ABCA8, CLU, CYP3A5). The expressional difference of IL8 and MMP9 were further validated by real-time quantitative RT-PCR and immunohistochemistry. The Gene Ontology analysis suggested a number of altered biological processes in OTSCCs, including enhancements in phosphate transport, collagen catabolism, I-kappaB kinase/NF-kappaB signaling cascade, extracellular matrix organization and biogenesis, chemotaxis, as well as suppressions of superoxide release, hydrogen peroxide metabolism, cellular response to hydrogen peroxide, keratinization, and keratinocyte differentiation in OTSCCs.</p> <p>Conclusion</p> <p>In summary, our study provided a transcriptomic signature for OTSCC that may lead to a diagnosis or screen tool and provide the foundation for further functional validation of these specific candidate genes for OTSCC.</p

Global Expression-Based Classification of Lymph Node Metastasis and Extracapsular Spread of Oral Tongue Squamous Cell Carcinoma

Regional lymph node metastasis is a critical event in oral tongue squamous cell carcinoma (OTSCC) progression. The identification of biomarkers associated with the metastatic process would provide critical prognostic information to facilitate clinical decision making for improved management of OTSCC patients. Global expressional profiles were obtained for 25 primary OTSCCs, where 11 cases showed lymph node metastasis (pN(+)) histologically and 14 cases were nonmetastatic (pN(-)). Seven of pN(+) cases also exhibited extracapsular spread (ECS) of metastatic nodes. Multiple expression indices were used to generate signature gene sets for pN(+/-) and ECS(+/-) cases. Selected genes from signature gene sets were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The classification powers of these genes were then evaluated using a logistic model, receiver operating characteristic curve analysis, and leave-one-out cross-validation. qRT-PCR validation data showed that differences at RNA levels are either statistically significant (P < .05) or suggestive (P < .1) for six of eight genes tested (BMP2, CTTN, EEF1A1, GTSE1, MMP9, and EGFR) for pN(+/-) cases, and for five of eight genes tested (BMP2, CTTN, EEF1A1, MMP9, and EGFR) for ECS(+/-) cases. Logistic models with specific combinations of genes (CTTN+MMP9+EGFR for pN and CTTN+EEF1A1+MMP9 for ECS) achieved perfect specificity and sensitivity. Leave-one-out cross-validation showed overall accuracy rates of 85% for both pN and ECS prediction models. Our results demonstrated that the pN and the ECS of OTSCCs can be predicted by gene expression analyses of primary tumors

Induction chemotherapy with docetaxel, cisplatin and fluorouracil followed by concurrent chemoradiotherapy or chemoradiotherapy alone in locally advanced non-endemic nasopharyngeal carcinoma

Objectives: To evaluate the efficacy of induction chemotherapy with docetaxel, cisplatin and fluorouracil (TPF) followed by concurrent chemoradiotherapy (IC + CCRT) or CCRT alone in non-endemic locally advanced nasopharyngeal carcinoma (NPC) patients. Materials and methods: Data of 106 patients with NPC treated from January 1999 to June 2012 with IC + CCRT (n = 58) or CCRT alone (n = 48) were retrospectively reviewed. Results: Median follow-up was 6.4 years. Distribution of age, performance status, stage and concurrent chemotherapy regimen were imbalanced between the two groups. The 5-year overall survival (OS) and progression-free survival (PFS) were not significantly different between IC + CCRT and CCRT groups (OS: 78.3% vs. 82.7%, p = 0.77; PFS: 72.5% vs. 68.2%, p = 0.81, respectively). There were less total cumulative incidence of grade 3-4 late radiation morbidity in the IC + CCRT group (44.8% vs. 70.8%, p = 0.01). Five-year OS for patients with post-IC complete response (CR), partial response (PR) and stable disease (SD) sub-groups were 100%, 79.4% and 60%, respectively. Conclusion: Compared with CCRT alone, IC (TPF regimen) + CCRT did not improve OS or PFS in patients with NPC, but less grade 3-4 late toxicities were observed. Responsiveness of IC may provide additional prognostic informatio

Influence of tumor-associated macrophages and HLA class I expression according to HPV status in head and neck cancer patients receiving chemo/bioradiotherapy

International audienc

MET Genetic Abnormalities Unreliable for Patient Selection for Therapeutic Intervention in Oropharyngeal Squamous Cell Carcinoma

Background: Identification of MET genetic alteration, mutation, or amplification in oropharyngeal squamous cell carcinoma (OPSCC) could lead to development of MET selective kinase inhibitors. The aim of this study was to assess the frequency and prognostic value of MET gene mutation, amplification, and protein expression in primary OPSCC. Methods: A retrospective chart review was conducted of patients treated for single primary OPSCC between January 2007 and December 2009. Pre-treatment OPSCC tissue samples were analyzed for MET mutations, gene amplification, and overexpression using Sanger sequencing, FISH analysis, and immunohistochemistry respectively. Univariate and multivariate analyses were used to analyze correlations between molecular abnormalities and patient survival. Results: 143 patients were included in this study. Six cases (4%) were identified that had a genetic variation, but previously described mutations such as p. Tyr1235Asp (Y1235D) or p.Tyr1230Cys (Y1230C) were not detected. There were 15 high polysomy cases, and only 3 cases met the criteria for true MET amplification, with >= 10% amplified cells per case. Immunohistochemistry evaluation showed 43% of cases were c-MET negative and in 57% c-MET was observed at the tumor cell level. Multivariate analysis showed no significant association between MET mutation, amplification, or expression and survival. Conclusions: Our study shows a low frequency of MET mutations and amplification in this cohort of OPSCC. There was no significant correlation between MET mutations, amplification, or expression and patient survival. These results suggest that patient selection based on these MET genetic abnormalities may not be a reliable strategy for therapeutic intervention in OPSCC