Discovery of potential serum protein biomarkers for lymph node metastasis in oral cancer

Chai, Yang; Zhang, Lifeng; Yang, Yan; Su, Trent; Charugundla, Prashant; Ai, Jiye; Messadi, Diana V.; Wong, David T.; Hu, Shen

doi:10.1002/hed.23870

Cited by 33 publications

(21 citation statements)

References 48 publications

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“…The most analyzed parameters in the literature are the pretreatment absolute count of neutrophils, monocytes, and lymphocytes, as well as the ratio between neutrophils and lymphocytes (neutrophil‐to‐lymphocyte ratio; NLR). These have been reported to be strong predictors of outcomes in a wide range of tumor models, including head and neck tumors . Moreover, to integrate the influence of all these variables, Qi et al have recently proposed an index called Systemic Inflammation Response Index (SIRI), which combines all the leukocytes of interest (neutrophils, monocytes, and lymphocytes), showing that it has prognostic capacity in pancreatic cancer …”

Section: Introductionmentioning

confidence: 99%

“…These have been reported to be strong predictors of outcomes in a wide range of tumor models, including head and neck tumors. [9][10][11][12][13][14][15][16][17][18][19][20] Moreover, to integrate the influence of all these variables, Qi et al have recently proposed an index called Systemic Inflammation Response Index (SIRI), which combines all the leukocytes of interest (neutrophils, monocytes, and lymphocytes), showing that it has prognostic capacity in pancreatic cancer. 21 Multiple studies have been published analyzing the prognostic capacity of pretreatment peripheral blood leukocytes (PBLs) using different cutoffs found using different methods.…”

Section: Introductionmentioning

confidence: 99%

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Pretreatment peripheral blood leukocytes are independent predictors of survival in oral cavity cancer

Valero

Zanoni

McGill

et al. 2019

Cancer

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Background Inflammation and immune surveillance evasion are cancer hallmarks. Peripheral blood leukocytes (PBLs) represent both. The aim of the current study was to examine PBLs as predictors of outcomes in oral cavity squamous cell carcinoma (OSCC), and to find specific cutoffs with the goal of including PBLs as host factor in patients' preoperative risk assessment. Methods Previously established head and neck squamous cell carcinoma (HNSCC) cutoffs were examined in an independent cohort of 1369 OSCC patients. Then optimal OSCC cutoffs were found and validated in the subset of patients with OSCC (n = 119) from the external HNSCC cohort. The PBLs analyzed were neutrophils, monocytes, and lymphocytes individually, the neutrophil‐to‐lymphocyte ratio (NLR), and a combined index using all PBLs called Systemic Inflammation Response Index (SIRI). Results All parameters were significant predictors of survival using the previous cutoffs. However, OSCC cutoffs stratified survival outcomes better. Considering neutrophils ≤4.8 × 109/L as reference, patients with 4.8–9.1 × 109/L neutrophils had 1.536 times higher risk of death (95% CI, 1.295‐1.822), and patients with ≥9.1 × 109/L had 3.076 times higher risk (95% CI: 2.170‐4.360). All PBLs maintained independent prognostic capacity in multivariable analysis. Neutrophils, NLR, and SIRI were significant predictors of survival when validating OSCC cutoffs in the external validation cohort. Conclusions Pretreatment peripheral blood neutrophils, NLR, and SIRI are the most robust independent predictors of overall survival among all PBLs in OSCC. The authors report externally validated cutoffs that demonstrate the feasibility of including PBLs as host features in the preoperative prognostication of OSCC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pretreatment peripheral blood leukocytes are independent predictors of survival in oral cavity cancer

Valero

Zanoni

McGill

et al. 2019

Cancer

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Section: Systematic Reviewmentioning

confidence: 99%

“…Chai et al, compared serum proteins from patients with node‐positive and node‐negative OSCC using quantitative iTRAQ‐LC‐ MS/MS approach . A total of 282 serum proteins were identified and quantified . Among them, the four candidate biomarkers: GSN, fibronectin, angiotensinogen (AGT), and haptoglobin (HP) were selected based on an observed >2‐fold change between node‐positive and node‐negative patients.…”

Section: Systematic Reviewmentioning

confidence: 99%

“…Their further validation by WB was conducted in an independent group of serum samples from patients with node‐positive ( n = 16) and node‐negative OSCCs ( n = 12). The WB analysis revealed that all four protein candidates were significantly upregulated in node‐positive compared to node‐negative OSCCs ( P < 0.05 for fibronectin and P < 0.01 for GSN, AGT and HP) …”

Section: Systematic Reviewmentioning

confidence: 99%

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Proteomics biomarkers for solid tumors: Current status and future prospects

Belczacka

Latosinska

Metzger

et al. 2018

Mass Spectrometry Reviews

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Cancer is a heterogeneous multifactorial disease, which continues to be one of the main causes of death worldwide. Despite the extensive efforts for establishing accurate diagnostic assays and efficient therapeutic schemes, disease prevalence is on the rise, in part, however, also due to improved early detection. For years, studies were focused on genomics and transcriptomics, aiming at the discovery of new tests with diagnostic or prognostic potential. However, cancer phenotypic characteristics seem most likely to be a direct reflection of changes in protein metabolism and function, which are also the targets of most drugs. Investigations at the protein level are therefore advantageous particularly in the case of in-depth characterization of tumor progression and invasiveness. Innovative high-throughput proteomic technologies are available to accurately evaluate cancer formation and progression and to investigate the functional role of key proteins in cancer. Employing these new highly sensitive proteomic technologies, cancer biomarkers may be detectable that contribute to diagnosis and guide curative treatment when still possible. In this review, the recent advances in proteomic biomarker research in cancer are outlined, with special emphasis placed on the identification of diagnostic and prognostic biomarkers for solid tumors. In view of the increasing number of screening programs and clinical trials investigating new treatment options, we discuss the molecular connections of the biomarkers as well as their potential as clinically useful tools for diagnosis, risk stratification and therapy monitoring of solid tumors.

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Suppression of OSCC malignancy by oral glands derived‐PIP identified by iTRAQ combined with 2D LC‐MS/MS

Wang

Yuan

Ren

et al. 2019

Journal Cellular Physiology

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Oral squamous cell carcinoma (OSCC) is the most common malignancy in head and neck cancer and a global cause of cancer‐related death. Due to the poor survival rates associated with OSCC, there is a growing need to develop novel technologies and predictive biomarkers to improve disease diagnosis. The identification of new cellular targets in OSCC tumors will benefit such developments. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)‐based proteomics analysis combined with 2‐dimensional liquid chromatography and tandem mass spectrometry (2D LC‐MS/MS) were used to identify differentially expressed proteins (DEPs) between tumor and normal tissues. Of the DEPs detected, the most significantly downregulated protein in OSCC tissue was prolactin‐inducible protein (PIP). Clonogenic and 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) experiments showed that the proliferation capacity of OSCC cells overexpressing PIP decreased due to cell cycle arrest at the G0/G1 checkpoint. Wound‐healing and transwell assay further showed that PIP overexpression also reduced the migration and invasion of OSCC cells. Immunohistochemistry (IHC) was used to analyze the expression in OSCC, indicating that PIP may be secreted by glandular cells and have an inhibitory effect on OSCC cells to produce. In western blot analysis, silencing studies confirmed that PIP mediates these effects through the AKT/mitogen‐activated protein kinase (MAPK) signaling axis in OSCC cells. Taken together, this study reveals PIP as a key mediator of OSCC cell growth, migration, and invasion through its effect on AKT/MAPK signaling.

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Discovery of potential serum protein biomarkers for lymph node metastasis in oral cancer

Cited by 33 publications

References 48 publications

Pretreatment peripheral blood leukocytes are independent predictors of survival in oral cavity cancer

Pretreatment peripheral blood leukocytes are independent predictors of survival in oral cavity cancer

Proteomics biomarkers for solid tumors: Current status and future prospects

Suppression of OSCC malignancy by oral glands derived‐PIP identified by iTRAQ combined with 2D LC‐MS/MS

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