Metabolic Biomarkers of Squamous Cell Carcinoma of the Aerodigestive Tract: A Systematic Review and Quality Assessment

Abstract

Introduction. Aerodigestive squamous cell carcinomas (ASCC) constitute a major source of global cancer deaths. Patients typically present with advanced, incurable disease, so new means of detecting early disease are a research priority. Metabolite quantitation is amenable to point-of-care analysis and can be performed in ASCC surrogates such as breath and saliva. The purpose of this systematic review is to summarise progress of ASCC metabolomic studies, with an emphasis on the critical appraisal of methodological quality and reporting. Method. A systematic online literature search was performed to identify studies reporting metabolic biomarkers of ASCC. This review was conducted in accordance with the recommendations of the Cochrane Library and MOOSE guidelines. Results. Thirty studies comprising 2117 patients were included in the review. All publications represented phase-I biomarker discovery studies, and none validated their findings in an independent cohort. There was heterogeneity in study design and methodological and reporting quality. Sensitivities and specificities were higher in oesophageal and head and neck squamous cell carcinomas compared to those in lung squamous cell carcinoma. The metabolic phenotypes of these cancers were similar, as was the kinetics of metabolite groups when comparing blood, tissue, and breath/saliva concentrations. Deregulation of amino acid metabolism was the most frequently reported theme. Conclusion. Metabolite analysis has shown promising diagnostic performance, especially for oesophageal and head and neck ASCC subtypes, which are phenotypically similar. However, shortcomings in study design have led to inconsistencies between studies. To support future studies and ultimately clinical adoption, these limitations are discussed.

Identification of a 5-lncRNA-Based Signature for Immune Characteristics and Prognosis of Lung Squamous Cell Carcinoma and Verification of the Function of lncRNA SPATA41

“…At the same time, simplicity is also one of its advantages, which can guide clinicians to evaluate the disease progression and prognosis more conveniently and accurately ( Ferrè et al, 2016 ; Schmitt and Chang, 2016 ; Peng et al, 2017 ; Kopp and Mendell, 2018 ). Our prognostic model aimed to determine the association between prognosis and basic characteristics and should be accurate and economical ( Iasonos et al, 2008 ; Balachandran et al, 2015 ; König et al, 2017 ; Goh et al, 2020 ). The nomogram included multiple independent variables and was easy for clinicians to evaluate the results and choose individual treatments for LUSC patients.…”

Salivary Biomarkers in Lung Cancer

“…One important caveat to using metabolic biomarkers for LC diagnosis was introduced in a systematic review of SCC of the aerodigestive tract [ 48 ]. Goh et al found that the various classes of metabolites (branch chain amino acids, fatty acids, amino acids, carbohydrates, inorganic compounds, and lipids) showed considerable overlap in expression in LSCC, oesophageal SCC, and head and neck SCC, though predominantly between OSCC and HNSCC.…”

Differential diagnosis of lung cancer and benign lung lesion using salivary metabolites: A preliminary study

“…As analytical technologies become more advanced, salivary biomarkers derived from genomics, transcriptomics, proteomics, microbiomics, and metabolomics have been reported as biomarkers for the clinical screening and detection of LC. [5][6][7][8][9][10] However, most of these studies analyzed differences between LC and controls, and there are not many reports that discriminate LC from benign lung lesions (BLL). 11,12 To the best of our knowledge, there has only been one study based on salivary metabolomic approaches for the discrimination of LC from BLL.…”

“…However, human saliva is increasingly being used as a diagnostic specimen for various diseases, because its collection is convenient and non‐invasive. As analytical technologies become more advanced, salivary biomarkers derived from genomics, transcriptomics, proteomics, microbiomics, and metabolomics have been reported as biomarkers for the clinical screening and detection of LC 5–10 . However, most of these studies analyzed differences between LC and controls, and there are not many reports that discriminate LC from benign lung lesions (BLL) 11,12 .…”