The MYH9 (Myosin heavy chain 9), an architecture component of the actomyosin cytoskeleton, has been reported to be dysregulated in several types of cancers. However, how this molecule contributes to cancer development is still obscure. This study deciphered the molecular function of MYH9 in head and neck cancer (HNC). Cellular methods included clonogenic survival, wound-healing migration, and Matrigel invasion assays. Molecular techniques included RT-qPCR, western blot, luciferase reporter assays, and flow cytometry. Clinical association studies were undertaken by TCGA data mining, Spearman correlation, and Kaplan-Meier survival analysis. We found that MYH9 was overexpressed in tumors and associated with poor prognosis in HNC patients. MYH9 promoted cell motility along with the modulation of the extracellular matrix (fibronectin, ITGA6, fascin, vimentin, MMPs). Also, MYH9 contributed to radioresistance and was related to the expression of anti-apoptotic and DNA repairing molecules (XIAP, MCL1, BCL2L1, ATM, RAD50, and NBN). Mechanically, MYH9 suppressed cellular ROS levels, which were achieved by activating the pan-MAPK signaling molecules (Erk, p38, and JNK), the induction of Nrf2 transcriptional activity, and the up-regulation of antioxidant enzymes (GCLC, GCLM, GPX2). The antioxidant enzyme GCLC was further demonstrated to facilitate cell invasion and radioresistance in HNC cells. Thus, MYH9 exerts malignant functions in HNC by regulating cellular ROS levels via activating the MAPK-Nrf2-GCLC signaling pathway. As MYH9 contributes to radioresistance and metastasis, this molecule may serve as a prognostic biomarker for clinical application. Furthermore, an in vivo study is emergent to support the therapeutic potential of targeting MYH9 to better manage refractory cancers.

To clarify the effect of induction chemotherapy (ICT) in patients with advanced pharyngeal and laryngeal squamous cell carcinoma (PLSCC) treated with concurrent chemoradiotherapy (CCRT). Patients with treatment-naïve nonmetastatic advanced PLSCC were stratified according to disease stage (III or IV) and resectability before being randomized to either a ICT/CCRT or CCRT arm. A cisplatin/tegafur-uracil/leucovorin regimen was administered during ICT and CCRT. The primary end point was overall survival (OS). We enrolled 151 patients during December 2006 to February 2011. The median follow-up of surviving patients was 54.5 months. The ICT/CCRT arm included more patients with hypopharynx cancer (57.1% vs 40.5%, p = 0.09) and N2 or N3 diseases (85.7% vs 74.4%, p = 0.02). In the ICT/CCRT and CCRT arms, the 5-year OS was 48.1% and 53.2% (p = 0.45); progression-free survival (PFS) was 31.8% and 55.6% (p = 0.015); and locoregional control (LRC) was 37.7% and 56.2% (p = 0.026), respectively. The adverse events and compliance to radiotherapy were similar. However, the proportion of patients receiving a total dose of cisplatin during CCRT <150 mg/m2 was higher in the ICT/CCRT arm (46.8% vs 16.2%; p = 0.000) and independently predicted poorer PFS and LRC in multivariate analysis. OS did not vary between the ICT/CCRT and CCRT arms. However, poorer compliance to CCRT and inferior LRC and PFS were observed in the ICT/CCRT arm. Optimizing the therapeutic ratio in both ICT and CCRT settings are necessary for developing a sequential strategy for patients with advanced-stage PLSCC.

To investigate the prognostic value of the relative maximum standardized uptake value (SUV) ratio between neck lymph node and primary tumor (NTR) measured by pretreatment 18F-FDG PET in patients with nasopharyngeal carcinoma (NPC). We retrospectively reviewed patients with non-disseminated NPC who underwent PET scans before radical intensity-modulated radiotherapy (IMRT). Receiver operating characteristic analysis was performed to identify the optimal cut-off value for NTR. The prognostic value of NTR for distant metastasis-free survival (DMFS) was evaluated using Kaplan-Meier method for survival analyses and Cox regression for multivariable analysis. Among the 437 eligible patients, the median follow-up time was 62.9 (range, 2.1-113.0) months. Patients with high NTR (NTR > 0.9181) experienced significantly worse DMFS (5-year 80.5% vs. 91.6%, P < 0.001). In the subgroup analysis, we found that patients with high NTR had significantly lower DMFS in T1-2 category (5-year 86.1% vs. 98.1%, P = 0.002), T3-4 category (5-year 71.5% vs. 86.2%, P = 0.010), N2-3 category (5-year 75.3% vs. 86.2%, P = 0.048), and stage IVA-B (5-year 69.8% vs. 85.4%, P = 0.012). Multivariable analysis showed that NTR was an independent prognostic factor for DMFS (HR 2.20, 95% CI 1.20-4.03, P = 0.011). Pretreatment NTR is an easily accessible but potential prognosticator for DMFS in NPC patients treated by IMRT, which may help in providing more personalized treatment or designing future clinical trials.

We prospectively investigated the prognostic value of imaging parameters for nasopharyngeal carcinoma (NPC) using dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI), and 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography (¹⁸F-FDG PET)/computed tomography (CT). Patients with stage III–IVb NPC underwent F-FDG PET/CT, DCE-MRI, and DWI before treatment. Kaplan-Meier and Cox-regression analyses were used to assess associations of PET and MRI imaging biomarkers with overall survival (OS) and recurrence-free survival (RFS). We used independent prognosticators to establish prognostic models; model performance was examined using Harrell’s concordance index (c-index). Sixty-one patients were available for analysis, as 13 patients died and 20 experienced recurrence. Total lesion glycolysis (TLG) (p = 0.002) from PET/CT and the initial area under the curve (iAUC) (p = 0.036) from DCE-MRI were identified as independent prognosticators of OS; Epstein-Barr virus (EBV) DNA (p = 0.027), the extracellular volume fraction (V_e) (p = 0.027) from DCE-MRI, and TLG/iAUC (p = 0.025) were significant predictors of RFS. The c-indices of the prognostic models incorporating TLG + iAUC in predicting OS and incorporating EBV DNA + V_e + TLG/iAUC in predicting RFS were 0.79 and 0.76, respectively. These were significantly higher than the corresponding c-indices of the TNM staging system (p = 0.047 and 0.025, respectively); they were also higher than those of models with only MRI or PET biomarkers. In conclusion, the combination of pretreatment DCE-MRI and ¹⁸F-FDG PET/CT imaging biomarkers helps survival prediction in advanced NPC. Integrating MRI perfusion with PET metabolism and plasma EBV information may aid clinicians in planning the optimal personalized management strategy.

Head and neck cancer (HNC) is one of the most prevalent cancers worldwide, accounting for approximately 5% of all cancers. While the underlying molecules and their pathogenetic mechanisms in HNC have yet to be well elucidated, recent studies have shown that dysregulation of lncRNAs may disrupt the homeostasis of various biological pathways. However, the understanding of lncRNAs in HNC is still limited by the lack of expression profiling. In the present study, we employed a systematic strategy to identify a panel of lncRNA associated with HNC. A cancer-related lncRNA profile PCR array was screened to explore potential molecules specific for HNC. A total of 55 lncRNAs were found to be dysregulated in HNC cells when compared to normal keratinocytes. Further analysis of the prognostic significance using The Cancer Genome Atlas (TCGA) database revealed 15 lncRNAs highly correlated with overall survival in HNC patients. Additionally, clinical sample expression analysis of the TCGA-HNSC cohort revealed 16 highly dysregulated lncRNAs in HNC, resulting in a combined 31-lncRNA signature panel that could predict prognosis. Validation of these molecules confirmed the considerable level of altered expressions in HNC cells, with XIST, HOXA11-AS, TSIX, MALAT1, WT1-AS, and IPW being the most prominently dysregulated. We further selected a molecule from our panel (XIST) to confirm the validity of these lncRNAs in the regulation of cancer aggressiveness. Gene ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses demonstrated that XIST participated in various cancer-related functions, including cell proliferation and metastasis. XIST silencing with the RNAi technique substantially reduced invasion and migration in several HNC cell lines. Thus, our study defined a 31-lncRNA panel as prognostic signatures in HNC. These perspective results provide a knowledge foundation for further application of these molecules in precision medicine.

To predict the outcome of reirradiation (re-RT) for oral cavity squamous cell carcinoma (OSCC). Eighty-three patients met the criterion of having previously irradiated OSCC treated via curative intent re-RT for recurrent or new primary OSCC. The exclusion criteria were a suboptimal dose (<45 Gy) for the first RT and palliative intent for the second irradiation. Re-RT was defined as at least 75% volume at second RT after receiving at least 45 Gy at the first RT. The 2-year locoregional progression-free survival (LRPFS) and overall survival (OS) rates were 20% and 28%. For LRPFS, four predictors were noted through univariate analyses: performance status (PS) (p = 0.001), a dose of at least 60 Gy (p = 0.001), stage IVB (p = 0.020), and surgery before re-RT (p = 0.041). In multivariate analyses, only PS (p = 0.005) and a dose of at least 60 Gy (p = 0.001) remained significant. For OS, PS (p = 0.001) and a dose of at least 60 Gy (p = 0.042) were still independently associated predictors, but surgery before re-RT became marginally beneficial (p = 0.053). For patients with a poor PS (ECOG = 2–3), the 2-year OS was only 4.5%. Twenty-nine percent of the patients experienced severe late complications (≥Grade 3), and 18% had new episodes of osteoradionecrosis during their follow-up. We identified PS and a re-RT dose ≥60 Gy as predictors for LRPFS and OS. Surgery before re-RT might improve OS. However, the treatment results of re-RT for OSCC were suboptimal. Prospective trials using modern RT techniques, in combination with new therapeutic drugs or radioenhancers, are warranted for improving these dismal outcomes.