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The Precision Medicine Approach in Oncology
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The second kit offered by the company, Epi proLungTM, is a confirmatory test to aid in the diagnosis of lung cancer based on a combination of proprietary DNA methylation biomarkers, SHOX2 and PTGER4. Currently marketed as a CE-marked IVD in Europe, it is claimed to provide additional molecular information for accurate diagnosis by evaluation of the mSHOX2 biomarker present in bronchial fluid obtained from patients with suspected lung cancer during routine bronchoscopy examination. A genomic gain of chromosome 3q involving the SHOX2 gene in lung cancer patients (i.e., methylation of SHOX2 gene DNA to give mSHOX2) has been observed in a number of recent clinical studies which supports mSHOX2 as a highly specific biomarker for lung cancer in bronchial fluid.
Liquid biopsy in head and neck squamous cell carcinoma: circulating tumor cells, circulating tumor DNA, and exosomes
Published in Expert Review of Molecular Diagnostics, 2020
Wen-Ying Yang, Lin-Fei Feng, Xiang Meng, Ran Chen, Wen-Hua Xu, Jun Hou, Tao Xu, Lei Zhang
ctDNA is more sensitive than CTCs in early detection and reflects tumor burden in real-time [66] (Figure 3). DNA methylation is the widely used epigenetic biomarker, which has been the hotspot of ctDNA researches in recent years. The SHOX2 and SEPT9 methylation show significant diagnostic value in HNSCC patients, which are the highest level of validation methylation biomarkers with high chemical stability [67]. It has been reported that SEPT9 methylation in cfDNA testing shows screening value in colorectal cancer and has recently received approval by the FDA [68–71]. Additionally, both SHOX2 and SEPT9 methylation can serve as diagnostic and prognostic parameters in pleural effusions and ascites [72]. Schröck and his colleges [73] discovered that the mean SHOX2/SEPT9 plasma level showed 52% sensitivity and 95% specificity in HNSCC diagnosis. The plasma level of SHOX2 and SEPT9 hypermethylation was closely related to the higher T and N category as well as a worse outcome compared to control. Another study suggested that quantitative and qualitative evaluation algorithms were equally reliable for both SHOX2 and SEPT9 methylation biomarkers in diagnosis and prognosis tests [74]. Therefore, SHOX2 and SEPT9 methylation tests provide much information about molecular staging, treatment choice, and post-therapeutic monitoring in HNSCC.
Tumor-specific methylations in circulating cell-free DNA as clinically applicable markers with potential to substitute mutational analyses
Published in Expert Review of Molecular Diagnostics, 2018
Schmidt et al. [94] could identify lung cancer patients as responders or non-responders based on the median level of SHOX2 methylated ctDNA after only one cycle of chemotherapy. This could potentially at an early time point spare patients ineffective treatment. Herbst et al. [95] used a similar approach but based on ROC analyses of the presence of HPP1 methylated ctDNA for colorectal cancer patients receiving chemotherapy and could predict response 3–4 weeks after the start of treatment.
Serum, plasma and saliva biomarkers for head and neck cancer
Published in Expert Review of Molecular Diagnostics, 2018
Lidia Maria Rebolho Batista Arantes, Ana Carolina De Carvalho, Matias Eliseo Melendez, André Lopes Carvalho
Using the full panel (CCNA1, DAPK, DCC, MGMT, MINT31, p16, and TIMP3), Carvalho and colleagues were able to show statistically significant associations of pretreatment salivary rinse methylation with poorer local control and poorer overall survival [112]. Regarding SHOX2 and SEPT9 genes, aberrant hypermethylation in plasma from HNSCC patients was correlated to a worst overall survival, indicating that these markers might be used for prognostic [113].