The role of blood biomarkers in the diagnosis of esophageal cancer

Posted by Master, Doctor Mai Vien Phuong - Department of Examination & Internal Medicine - Vinmec Central Park International General Hospital

Several candidate biomarkers for esophageal cancer have been proposed. However, their translation into clinical use has been slow. Biomarkers can be broadly defined as quantifiable parameters that differentiate normal processes from pathological ones with applications for diagnosis, prognosis, and treatment adjustment of patients. Since an important group of studies has been performed evaluating tissue-based biomarkers in esophageal cancer, this review has intentionally focused on minimally invasive and non-invasive methods for the detection of esophageal cancer. oesophageal cancer, markers circulating mainly in the blood and emerging areas of the breath and odor biomarkers. The development of powerful, minimally invasive, cost-effective biomarkers for early cancer will change current diagnostic, prognostic, and surveillance models and may open up possibilities population screening.

The diagnosis of esophageal cancer and its premalignant lesions is currently limited to endoscopy and subsequent biopsy analysis. Endoscopy is a highly invasive and expensive diagnostic procedure and the current gold standard diagnostic technique for esophageal cancer and its precancerous lesions. Standard white light endoscopy is limited in its scope, limited to identifying macroscopic abnormalities that may indicate cancer, such as nodules and ulcers, and therefore cannot identify Early lesions appear to be grossly normal. While Barrett's esophagus is visible endoscopically, dysplasia in the Barrett segment is more difficult to identify because the lesions are often flat and difficult to distinguish from the surrounding non-dysplastic columnar epithelium.
Classification of dysplasia is subjective and studies have shown that distinctions between dysplasia types vary widely among pathologists, leading to misdiagnosis and unnecessary interventional procedures. Likewise, random biopsy procedures are prone to sampling errors, adding to the potential for misdiagnosis.
Endoscopic surveillance and biopsy are often recommended for patients with Barrett's esophagus, to diagnose esophageal cancer in its earliest stages. Because of the low rate of progression of early lesions, such as Barrett's esophagus to adenocarcinoma, and the cost of endoscopic follow-up, the application of current diagnostic procedures in cancer surveillance Esophageal cancer may not be effective, and screening programs have never been considered viable. Therefore, there is an urgent need for the development of more selective and less invasive diagnostic techniques for individuals at risk for esophageal cancer.
Urgent biomarkers of esophageal cancer
Blood biomarkers
Autoantibodies have attracted interest as serologic markers for esophageal cancer, due to their stability and their presence in serum samples. With improvements in antibody detection technology raising the detection limit, there is increasing interest in the use of autoantibodies as diagnostic and prognostic biomarkers for esophageal cancer. Perhaps the most comprehensively studied is the tumor suppressor gene, TP53. The protein product of TP53 is a nuclear phosphoprotein and in normal human plasma, TP53 protein and anti-p53 antibodies are absent. The p53 mutation can cause the accumulation of non-functional proteins with increased stability and longer half-lives compared with native proteins. Anti-p53 production has subsequently been detected in the tissues, blood, and other body fluids of several types of cancer, including esophageal cancer. A meta-analysis by Zhang et al summarizing the diagnostic value of anti-p53 for esophageal cancer found that esophageal cancer patients had a seven-fold increased risk of plasma anti-p53 positivity. compared with the control group without cancer. However, despite its high specificity, the authors reported low sensitivity, suggesting limited clinical application.

Recently, a systematic review investigated the diagnostic utility of 35 different circulating autoantibodies, both singly and in combination, as biomarkers for the early detection of esophageal cancer. Although the study did not differentiate between the two types of esophageal cancer, the majority of the studies included in the review were esophageal squamous cell carcinomas, the worldwide burden of this variant compared with this type. adnexal adenocarcinoma. Although the majority of the studies reviewed reported a positive association between their candidate biomarkers and esophageal cancer, given the high specificity reported, the sensitivity values ​​are often too low to be of any clinical significance. However, the combination of autoantibodies slightly improved mean sensitivity. The authors also performed a meta-analysis of the diagnostic value of anti-p53, reporting a significant association between serum anti-p53 and esophageal cancer, with a sensitivity of 91.4% and a sensitivity of 91.4%. specificity was 65% compared with their previous findings on meta-analyses against p53.
Six serum biochemical markers including anti-p53, carcinoembryonic antigen, squamous cell cancer antigen, cytokeratin fragment 21-1 (CYFRA21-1), vascular endothelial growth factor-C and microRNA (miRNA) ) was reviewed in a meta-analysis by Zhang et al. Although each biomarker candidate was associated with positive odds ratios for esophageal cancer and high specificity values ​​by the receiver activity-characteristics curves, the sensitivity for each trial was low, with high variability between studies. Although the authors suggest that a combination of serological markers is likely to confer better sensitivity and specificity, it is more likely that better-designed multicenter studies are needed. , more robust, for better optimization and validation of candidate serum biochemical markers.
Circulatory tumor cells (CTCs) are derived from the primary tumor, and are released into the systemic circulation, where they can form micro-metastases. Various tests have been developed and used to evaluate the diagnostic and prognostic capabilities of CTCs in several types of cancer, including breast, colorectal, gastric, and esophageal cancers. A recent meta-analysis by Qiao et al aimed to determine the association between CTCs with clinical and prognostic features (tumor stage, lymph node metastasis, distant metastasis, and survival time of CTCs). patients) in esophageal cancer. The presence of CTCs is strongly correlated with poor overall survival, and predicts poor progression-free survival in Asian populations with esophageal squamous cell carcinoma. CTCs also correlate with venous invasion and metastasis to local lymph nodes (stage N). New methodologies for the quantification of circulating tumor DNA may also offer new diagnostic potential, but further research is needed to evaluate this possibility.
Blood biomarkers for esophageal cancer represent new tools for early detection and prognosis. However, despite the large number of candidate markers that have been published, there are still very few promising, well-designed multicenter validation studies for both esophageal squamous cell carcinoma and esophageal squamous cell carcinoma. and esophageal adenocarcinoma.
Role of miRNA strand
MiRNA is a single-stranded, non-coding RNA that can regulate the expression of genes and proteins. miRNAs are highly expressed in stable form, with high inter-individual consistency in a variety of extracellular fluids including serum and plasma, and have attracted attention as biomarkers for cancer. mail and illness. Recent studies have reported circulating plasma/serum miRNAs as potential diagnostic and prognostic markers in several gastrointestinal cancers - esophageal squamous cell carcinoma, esophageal adenocarcinoma, stomach and colon. Although still an emerging area of ​​research, recent meta-analyses have highlighted the potential of circulating miRNAs in the detection of esophageal cancer.

A review by Wang et al of eight manuscripts investigated a total of 16 different miRNAs in the serum and saliva of patients with Asian esophageal squamous cell carcinoma. The authors reported relatively high sensitivity and specificity values ​​for combined and single miRNA markers, suggesting several diagnostic applications. The prognostic utility of miRNAs was also considered, Fu et al. reported 39 potentially prognostic miRNAs in 25 individual studies. miR-21 and miR-375 were found to be prognostic about overall survival. However, the small number of manuscripts that can be included in the study and the lack of validation studies performed using miRNA markers limit the conclusions that can be drawn for translation application. . A more comprehensive meta-analysis by Fu et al found that although increased expression of miR-21 and decreased expression of miR-375 were significantly associated with poor overall survival in breast cancer. esophageal cancer, both miR-21 and miR-275 are associated with a low risk.
Circulating miRNAs have also been studied as biomarkers of esophageal adenocarcinoma and pointer status, Barrett's esophagus. In a retrospective study of biostriped serum samples from patients with esophageal cancer, Chiam et al identified five miRNA ratios, derived from ten unique miRNAs capable of discriminating against esophageal cancer. adenocarcinoma of the esophagus compared with non-dysplastic Barrett's esophagus and healthy controls. The prediction accuracy of the miRNA ratio was enhanced with the stepwise addition of the miRNA ratio to the analysis of blood samples of cancer patients, highlighting the potential of biomarker-incorporating approaches to enhance specificity and sensitivity of the test.
CONCLUSION
Current diagnostic and monitoring procedures for esophageal cancer are invasive, costly and inadequate for early detection. Recent advances have been made in the development and validation of novel minimal and non-invasive biomarkers for esophageal cancer. Although several new serological markers have been investigated, they have not yet been translated into use as tools in clinical practice. Circulating antip53 and CTCs have shown the most promise as diagnostic and prognostic markers of esophageal cancer, with recent meta-analyses supporting their use. However, the absence of well-designed, robust clinical validation trials in large patient populations greatly limited the power of these meta-analyses. This is highlighted by the lack of differentiation between esophageal squamous cell carcinoma and esophageal adenocarcinoma,
Narrow band endoscopic technique is the best method for cancer screening esophagus, stomach. Currently, this technique is being applied routinely at Vinmec International General Hospital. With a team of experienced and deep gastroenterologists, we have fully mastered the modern diagnostic endoscopy system, including the endoscopy system with narrow light frequency band to bring patient comfort. , satisfied and assured about the perfect service quality for diagnosis and treatment of diseases in the upper digestive system.

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