Connecting multiple microenvironment proteomes uncovers the biology in head and neck cancer

Abstract

The poor prognosis of head and neck cancer (HNC) is associated with metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision-making. Protein profiles are strictly associated with immune modulation across datasets, and this provides the basis for investigating immune markers associated with metastasis. The proteome of LN metastatic cells recapitulates the proteome of the primary tumor sites. Conversely, the LN microenvironment proteome highlights the candidate prognostic markers. By integrating prioritized peptide, protein, and transcript levels with machine learning models, we identify nodal metastasis signatures in blood and saliva. We present a proteomic characterization wiring multiple sites in HNC, thus providing a promising basis for understanding tumoral biology and identifying metastasis-associated signatures.

Mapping Conformational Changes in the Saliva Proteome Potentially Associated with Oral Cancer Aggressiveness

“…This protein was also previously identified with higher abundance in nonmalignant cells from lymph nodes compared to primary tumor’s cells . Although TKT has a recognized prognostic role in tumoral tissue, , its contribution to saliva has yet to be determined.…”

“…Prioritization was based on the following criteria: (1) top hit in ranking attribute method analysis; (2) clinical correlation with prognostic features; (3) identifications in previous studies as differentially abundant proteins from nonmalignant cells of primary OSCC tumors compared to committed lymph nodes …”

“…This protein was also previously identified with higher abundance in nonmalignant cells from lymph nodes compared to primary tumor's cells. 20 Although TKT has a recognized prognostic role in tumoral tissue, 21,22 its contribution to saliva has yet to be determined. TKT enzymes are phosphorylated in Thr380 by AKT, 23 and the structural changes detected by LiP-MS encompass this region, implying a role of phosphorylation in TKT conformational change, more specifically in lymph node metastasis condition.…”

“…Prioritization was based on the following criteria: (1) top hit in ranking attribute method analysis; (2) clinical correlation with prognostic features; (3) identifications in previous studies as differentially abundant proteins from nonmalignant cells of primary OSCC tumors compared to committed lymph nodes. 20 Three filter approaches implemented in the data mining tool Waikato Environment for Knowledge Analysis (WEKA) v.3.8.5 were applied in the LiP data set. They were (i) information gain attribute evaluation, (ii) chi-square attribute evaluation, and (iii) support vector machine (SVM) attribute evaluation.…”

PanCanSurvPlot: A Large-scale Pan-cancer Survival Analysis Web Application

“…The detection of marker levels in patients prior to treatment is widely used to assess the occurrence of clinical events, disease recurrence or progression, and survival outcomes, thereby helping clinicians and researchers guide the monitoring of cancer patients and make decisions about personalized treatment [1][2][3]. Tumor prognostic markers are currently being studied in numerous areas, including genomics [4,5], transcriptomics [6][7][8], proteomics [9,10], metabolomics [11], and epigenomics [12,13]. Among these, the investigation of transcriptomic prognostic markers has been a hot area of research in the last decade owing to the rapid development of microarray and high-throughput sequencing technologies, which researchers have used to uncover a large number of potential molecular mechanisms of gene expression differences leading to disease development and clinical applications.…”