Major depressive disorder (MDD) is a complex psychiatric disorder characterized by changes in both resting state and stimulus-evoked activity. Whether resting state changes are carried over to stimulus-evoked activity, however, is unclear. We conducted a combined rest (3 min) and task (three-stimulus auditory oddball paradigm) EEG study in n=28 acute depressed MDD patients, comparing them with n=25 healthy participants. Our focus was on the temporal dynamics of both resting state and stimulus-evoked activity for which reason we measured peak frequency (PF), coefficient of variation (CV), Lempel-Ziv complexity (LZC), and trial-to-trial variability (TTV). Our main findings are: i) atypical temporal dynamics in resting state, specifically in the alpha and theta bands as measured by peak frequency (PF), coefficient of variation (CV) and power; ii) decreased reactivity to external deviant stimuli as measured by decreased changes in stimulus-evoked variance and complexity—TTV, LZC, and power and frequency sliding (FS and PS); iii) correlation of stimulus related measures (TTV, LZC, PS, and FS) with resting state measures. Together, our findings show that resting state dynamics alone are atypical in MDD and, even more important, strongly shapes the dynamics of subsequent stimulus-evoked activity. We thus conclude that MDD can be characterized by an atypical temporal dynamic of its rest–stimulus interaction; that, in turn, makes it difficult for depressed patients to react to relevant stimuli such as the deviant tone in our paradigm.

Laryngeal squamous cell carcinoma (LSCC) from different subsites have distinct presentations and prognosis. In this study, we carried out a multiomic comparison of LSCC subsites. The Cancer Genome Atlas (TCGA) LSCC cohort was analyzed in the R statistical environment for differences between supraglottic and glottic cancers in single nucleotide variations (SNVs), copy number alterations (CNAs), mRNA abundance, protein abundance, pathway overrepresentation, tumor microenvironment (TME), hypoxia status, and patient outcome. Supraglottic cancers had significantly higher overall and smoking-associated SNV mutational load. Pathway analysis revealed upregulation of muscle related pathways in glottic cancer and neural pathways in supraglottic cancer. Proteins involved in cancer relevant signaling pathways including PI3K/Akt/mTOR, the cell cycle, and PDL1 were differentially abundant between subsites. Glottic and supraglottic tumors have different molecular profiles, which may partially account for differences in presentation and response to therapy.

Loss of the 3p chromosome arm has previously been reported to be a biomarker of poorer outcome in both human papillomavirus (HPV)-positive and HPV-negative head and neck cancer. However, the precise operational measurement of 3p arm loss is unclear and the mutational profile associated with the event has not been thoroughly characterized. We downloaded the clinical, single nucleotide variation (SNV), copy number aberration (CNA), RNA sequencing, and reverse phase protein assay (RPPA) data from The Cancer Genome Atlas (TCGA) and The Cancer Proteome Atlas HNSCC cohorts. Survival data and hypoxia scores were downloaded from published studies. In addition, we report the inclusion of an independent Memorial Sloan Kettering cohort. We assessed the frequency of loci deletions across the 3p arm separately in HPV-positive and -negative disease. We found that deletions on chromosome 3p were almost exclusively an all or none event in the HPV-negative cohort; patients either had <1% or >97% of the arm deleted. 3p arm loss, defined as >97% deletion in HPV-positive patients and >50% in HPV-negative patients, had no impact on survival (p > 0.05). However, HPV-negative tumors with 3p arm loss presented at a higher N-category and overall stage and developed more distant metastases (p < 0.05). They were enriched for SNVs in TP53, and depleted for point mutations in CASP8, HRAS, HLA-A, HUWE1, HLA-B, and COL22A1 (false discovery rate, FDR < 0.05). 3p arm loss was associated with CNAs across the whole genome (FDR < 0.1), and pathway analysis revealed low lymphoid–non-lymphoid cell interactions and cytokine signaling (FDR < 0.1). In the tumor microenvironment, 3p arm lost tumors had low immune cell infiltration (FDR < 0.1) and elevated hypoxia (FDR < 0.1). 3p arm lost tumors had lower abundance of proteins phospho-HER3 and ANXA1, and higher abundance of miRNAs hsa-miR-548k and hsa-miR-421, which were all associated with survival. There were no molecular differences by 3p arm status in HPV-positive patients, at least at our statistical power level. 3p arm loss is largely an all or none phenomenon in HPV-negative disease and does not predict poorer survival from the time of diagnosis in TCGA cohort. However, it produces tumors with distinct molecular characteristics and may represent a clinically useful biomarker to guide treatment decisions for HPV-negative patients.

Background Numerous studies of head and neck squamous cell carcinoma (HNSCC) have demonstrated disparate outcomes by race and ethnicity. Beyond known associations with socioeconomic variables, whether these are also associated with differences in tumor molecular composition has thus far been poorly explored. Methods We downloaded clinical and multiplatform molecular data from The Cancer Genome Atlas and other published studies. These were compared between non‐Hispanic Black (n = 43) and White (n = 354) patients with non‐HPV‐related tumors, using multivariable models. Publicly available validation cohorts were used. Results Black patients had poorer progression‐free survival than White patients. Tumors of Black patients had greater copy number aberrations, and increased SFRP1 methylation and miRNA‐mediated PRG4 silencing associated with poor survival. PI3K/AkT/mTOR pathway proteins were differentially expressed. Conclusions There are molecular differences between tumors of Black and White patients that may partially account for differences in survival. These may inform targeted treatment decisions to achieve equitable outcomes.

Background: Numerous studies have demonstrated poorer outcomes by race/ethnicity in head and neck squamous cell carcinoma (HNSCC). Although some studies have identified differences in socioeconomic status and access to care as important factors affecting outcomes, differences in the genomic and extracellular composition of tumors from patients of different races/ethnicities have yet to be explored. Methods: We downloaded the clinical information, single nucleotide variation (SNV), copy number aberration (CNA), mRNA sequencing, and reverse phase protein assay (RPPA) data from The Cancer Genome Atlas (TCGA) and The Cancer Proteome Altas HNSCC cohorts. Survival data and hypoxia scores were downloaded from published studies. We stratified the cohort into combined racio-ethnic groups (REG) as follows: White/Non-Hispanic (White), Hispanic/Latino (Hispanic), Black/African American (Black), Asian, American Indian/Non-Hispanic (Indigenous American). Cases positive for human papillomavirus (HPV) occurred almost exclusively among White patients (68/71) and thus they were excluded. Results: The HPV-negative cohort contained 354 White, 43 Black, 22 Hispanic and 11 Asian and 1 Indigenous American patient. Black patients had poorer overall and progression-free survival than White patients on univariate and multivariate analysis, respectively (p&lt;0.05). There were no significant SNV differences between any REGs after false discovery rate (FDR) correction. However, there was a large number of CNAs with higher frequency in Black patients compared to White patients (2294 shallow deletions, 96 gains, FDR&lt;0.1). In particular, loss of the 3p chromosome arm was markedly more frequent in tumors from Black patients (p&lt;0.01), but was not associated with poorer prognosis. From the RPPA data we found 31 cancer-associated proteins and phosphoproteins differentially expressed between Black and White patients (FDR&lt;0.1). These included proteins in the PI3K/Akt/mTOR pathway in White patients, and N-cadherin and Hsp70 in Black patients. Deconvolution of the mRNA sequencing counts revealed differences in lymphocyte infiltration of the tumor microenvironment between Black, Hispanic, and White patients (FDR&lt;0.1). Black patients also had more hypoxic tumors than White patients (FDR&lt;0.1). Conclusions: In summary, we have identified important biological differences between tumors of different REGs that may partially account for differences in survival and inform targeted treatment decisions towards equitable outcomes. Citation Format: Hugh A.J. Kim, Peter Y.F. Zeng, Alana Sorgini, Mushfiq H. Shaikh, Neil Mundi, Halema Khan, Danielle MacNeil, Mohammed I. Khan, Krupal Patel, Adrian Mendez, John Yoo, Kevin Fung, Pencilla Lang, David A. Palma, Joe S. Mymryk, John W. Barrett, Paul C. Boutros, Anthony C. Nichols. Multi-omic disparities in head and neck squamous cell carcinomas in patients of different racio-ethnic backgrounds [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PR11.

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