Detection of Loss of Heterozygosity in cfDNA of Advanced EGFR- or KRAS-Mutated Non-Small-Cell Lung Cancer Patients

Boldrin, Elisa; Nardo, Giorgia; Zulato, Elisabetta; Bonanno, Laura; Polo, Valentina; Frega, Stefano; Pavan, Alberto; Saggioro, Daniela

doi:10.3390/ijms21010066

Cited by 5 publications

(3 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mutations range in size and can affect anywhere from a single DNA base pair to a large segment of a chromosome that includes multiple genes. The mutation analysis of cfDNA in specifics genes as KRAS, TP53, BRAF, epidermal growth factor receptor (EGFR), and adenomatous polyposis coli (APC) has been demonstrated great clinical relevance [157][158][159][160][161][162].…”

Section: Mutationsmentioning

confidence: 99%

Properties and Application of Cell-Free DNA as a Clinical Biomarker

Miranda

Baraúna

Santos

et al. 2021

IJMS

View full text Add to dashboard Cite

Biomarkers are valuable tools in clinical practice. In 2001, the National Institutes of Health (NIH) standardized the definition of a biomarker as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. A biomarker has clinical relevance when it presents precision, standardization and reproducibility, suitability to the patient, straightforward interpretation by clinicians, and high sensitivity and/or specificity by the parameter it proposes to identify. Thus, serum biomarkers should have advantages related to the simplicity of the procedures and to the fact that venous blood collection is commonplace in clinical practice. We described the potentiality of cfDNA as a general clinical biomarker and focused on endothelial dysfunction. Circulating cell-free DNA (cfDNA) refers to extracellular DNA present in body fluid that may be derived from both normal and diseased cells. An increasing number of studies demonstrate the potential use of cfDNA as a noninvasive biomarker to determine physiologic and pathologic conditions. However, although still scarce, increasing evidence has been reported regarding using cfDNA in cardiovascular diseases. Here, we have reviewed the history of cfDNA, its source, molecular features, and release mechanism. We also show recent studies that have investigated cfDNA as a possible marker of endothelial damage in clinical settings. In the cardiovascular system, the studies are quite new, and although interesting, stronger evidence is still needed. However, some drawbacks in cfDNA methodologies should be overcome before its recommendation as a biomarker in the clinical setting.

show abstract

Section: Mutationsmentioning

confidence: 99%

Properties and Application of Cell-Free DNA as a Clinical Biomarker

Miranda

Baraúna

Santos

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…A similar study showed the relevance of this mutation upon the analysis of ctDNA [ 61 , 62 ]. In addition, numerous lung-cancer-related mutations (e.g., in ALK, EGFR , and pmKRAS ) as well as the loss of heterozygosity, microsatellite instability, and gene methylation, are also readily detected in these cfDNA [ 62 , 63 ]. The recurrence and prognosis of lung carcinoma was also reported to be efficiently detected via cfDNA analysis, contributing to rationalized clinical decisions [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Blood-Derived Exosomal hTERT mRNA in Patients with Lung Cancer: Characterization and Correlation with Response to Therapy

et al. 2023

View full text Add to dashboard Cite

Background: Telomerase (human telomerase reverse transcriptase (hTERT) is considered a hallmark of cancer, being active in cancer cells but repressed in human somatic cells. As such, it has the potential to serve as a valid cancer biomarker. Exosomal hTERT mRNA can be detected in the serum of patients with solid malignancies but not in healthy individuals. We sought to evaluate the feasibility of measuring serum exosomal hTERT transcripts levels in patients with lung cancer. Methods: A prospective analysis of exosomal hTERT mRNA levels was determined in serum-derived exosomes from 76 patients with stage III–IV lung cancer (11 SCLC and 65 NSCLC). An hTERT level above RQ = 1.2 was considered “detectable” according to a previous receiver operating characteristic curve (ROC) curve. Sequential measurements were obtained in 33 patients. Demographic and clinical data were collected retrospectively from patients’ charts. Data on response to systemic therapy (chemotherapy, immunotherapy, and tyrosine kinase inhibitors) were collected by the treating physicians. Results: hTERT was detected in 53% (40/76) of patients with lung cancer (89% of SCLC and 46% of NSLCC). The mean hTERT levels were 3.7 in all 76 patients, 5.87 in SCLC patients, and 3.62 in NSCLC patients. In total, 25 of 43 patients with sequential measurements had detectable levels of hTERT. The sequential exosomal hTERT mRNA levels reflected the clinical course in 23 of them. Decreases in hTERT levels were detected in 17 and 5 patients with partial and complete response, respectively. Eleven patients with a progressive disease had an increase in the level of exosomal hTERT, and seven with stable disease presented increases in its exosomal levels. Another patient who progressed on the first line of treatment and had a partial response to the second line of treatment exhibited an increase in exosomal hTERT mRNA levels during the progression and a decrease during the response. Conclusions: Exosomal hTERT mRNA levels are elevated in over half of patients with lung cancer. The potential association between hTERT levels and response to therapy suggests its utility as a promising cancer biomarker for response to therapy. This issue should be further explored in future studies.

show abstract

“…Lung cancer is one of the malignant tumors with a high incidence, and malnutrition is a global public health problem for the disease (Adie et al, 2020;Boldrin et al, 2019;Canale et al, 2019). According to statistics, the incidence of malnutrition in hospitalized patients with lung cancer is about 20-50% (Andrews Wright & Goss, 2019;Arroyo et al, 2019).…”

Section: Introductionmentioning

confidence: 99%