Blood-based tumor mutational burden testing: current research and challenges / 中华检验医学杂志

Blood-based tumor mutational burden (bTMB) calculated based on next-generation sequencing (NGS) to examine the circulating tumor DNA (ctDNA) is often considered as a non-invasive biomarker-candidate predicting the clinical benefit of patients who received immunotherapy. Some recent evidence indicates that the alteration of bTMB related characters is often associated with objective response rates of patients to cancer immunotherapy, but has limited predictive value in long-term prognostic benefit. The predictive efficacy of bTMB is affected by many factors such as the abundance of circulating tumor DNA and tumor heterogeneity, and adjusted bTMB examination after correcting for interfering factors can better predict the long-term survival benefit of immunotherapy. Application of bTMB testing still needs to overcome methodological, economic, and standardization challenges during clinical application.

Clinical application of comprehensive genomic profiling based on circulating tumor DNA in patients with advanced lung cancer / 中华检验医学杂志

Objective:This work aims to evaluate the clinical values of comprehensive genomic profiling examination based on circulating tumor DNA (ctDNA) in advanced lung cancer patients.Methods:This is a single-center, retrospective study that collected peripheral blood samples from patients with advanced lung cancer and performed gene mutation analysis using the TruSight Oncology 500 ctDNA assay kits. Between February 2022 and March 2023, a total of 82 patients were enrolled in Zhongshan Hospital, Fudan University, and 76 patients were included in the final analysis.According to the AMP/ASCO/CAP guidelines, mutations of targeted genes were divided into four levels (Tier I-IV), and the effectiveness of targeted therapy guided by ctDNA was evaluated. Descriptive statistics were used for basic characteristics, and the analysis of factors related to tumor mutational burden (TMB) was performed using the rank-sum test.Results:The ctDNA detection success rate was 92.7%(76/82).The median turnaround time for ctDNA testing was 10.5 days (9,13 days). At least one actionable mutation (Tier I or Ⅱ) was detected in 82.9%(63/76) of patients, and 28.6% (18/63) of patients received matched therapy, achieving a disease control rate of 18/18 and an objective response rate of 12/18.Conclusion:Comprehensive genomic profiling based on ctDNA can effectively identify actionable alterations in patients with advanced lung cancer and provide valuable information for matched therapy.

High Positive Predictive Value of Multitarget Stool DNA After Aerodigestive Tract Radiotherapy.

BACKGROUND AND AIMS: Multitarget stool DNA (mt-sDNA) is approved for average-risk colorectal cancer screening; test performance in persons with prior radiation therapy (RT) has not been studied. RT can induce gastrointestinal bleeding and alter DNA methylation, which may affect mt-sDNA accuracy. Among patients previously treated with RT, we aimed to measure the positive predictive value (PPV) of mt-sDNA and compare these results to historical estimates of mt-sDNA PPV among average-risk patients. METHODS: After institutional review board approval, we conducted a retrospective cohort study of a multisite academic and community-based practice. Patients with RT and subsequent mt-sDNA use during the study period (2014-2016) were identified. The findings at diagnostic colonoscopy were compared with published reports among average-risk patients. Nominal P values were generated by 2-tailed Fisher's exact testing in comparisons of colorectal neoplasia (CRN) rates between groups. RESULTS: There were 220 patients who had RT before mt-sDNA testing. RT was delivered along the aerodigestive tract in 108 patients. Mt-sDNA tests were positive in 45 of 220 patients (20%), and colonoscopy findings were available for 42; 31 of 42 patients (74%) had CRN. PPV by mt-sDNA was similar when stratified by site of prior RT (along vs outside the aerodigestive tract; P = 1.00). Detection of advanced CRN (36%) was nominally higher than previously published retrospective (27%) and prospective (20%) studies. The median time from the start of RT to mt-sDNA use was 7 (interquartile range, 3-14) years. CONCLUSION: With a test positivity rate and PPV for CRN similar to reports among average-risk patients, prior RT does not appear to adversely affect mt-sDNA performance.

Multi-Target Stool DNA Testing for Colorectal Cancer Screening: Emerging Learning on Real-world Performance.

PURPOSE OF REVIEW: Multi-target stool DNA (MT-sDNA) was approved in 2014 for use in screening average-risk patients for colorectal cancer (CRC). Here, we highlight recent literature from post-market studies to provide an update on clinical use and utility not possible from pre-approval studies. RECENT FINDINGS: MT-sDNA has been included in major society guidelines as an option for colorectal cancer screening, and has seen exponentially increasing use in clinical practice. MT-sDNA appears to be attracting new patients to CRC screening, and patient adherence to diagnostic colonoscopy after a positive MT-sDNA test is high. Approximately two-thirds of these patients are found to have colorectal neoplasia (CRN), 80% of whom have at least one right-sided lesion; 1 in 3 will have advanced CRN. High yield of CRN is due not only to post-screening increase in probability but also likely improved endoscopist attention. In those with a negative high-quality colonoscopy after positive MT-sDNA test ("false positive MT-sDNA"), further interventions do not appear to be necessary. SUMMARY: MT-sDNA is a promising tool to improve rates and quality of CRC screening. Further investigation should examine MT-sDNA performance in populations at increased risk for CRC, and as an interval test after colonoscopy to detect potentially missed lesions.

Application of circulating free DNA in the diagnosis and treatment of hepatocellular carcinoma / 临床肝胆病杂志

Hepatocellular carcinoma has a low early diagnostic rate, and there is a lack of highly sensitive and specific tumor markers. In recent years, fluid biopsy technique, represented by circulating free DNA (cfDNA), has become an auxiliary method for the diagnosis of cancer and has attracted more and more attention due to its advantages of noninvasiveness, convenience, and repeatability. With reference to the recent studies in China and foreign countries, this article summarizes and analyzes the advances in cfDNA in the diagnosis and treatment of hepatocellular carcinoma from the aspects of biological characteristics, detection techniques, and clinical application, so as to provide a basis for clinical diagnosis and treatment.

[Combined detection of KRAS, NRAS, BRAF and PIK3CA mutations in the plasma and tumor tissues of colorectal cancer patients].

Objective: To analyze the concordance of KRAS, NRAS, BRAF and PIK3CA gene mutations detected in plasma and matched tumor tissues in colorectal cancer patients, in order to provide good evidences to support plasma could be a potential surrogate of tumor tissue for gene mutation test. Methods: One hundred and seventy-five cases of colorectal cancer were collected at the First Hospital of Jilin University, from October 2016 to October 2017.There were 101 males and 74 females, their ages ranged from 28 to 85 years,with median age of 59 years. The KRAS, NRAS, BRAF and PIK3CA gene mutations in the plasma and paired tumor specimens of all patients were detected by next generation sequencing. Results: The results of tissue samples test were gold standard. Comparison of the four genes showed that concordance rates between plasma and tissue samples were 81.1%(Kappa=0.543), 99.4%(Kappa=0.886), 99.4% (Kappa=0.886) and 97.7%(Kappa=0.714) respectively for KRAS, NRAS, BRAF and PIK3CA. The plasma detection rates of these genes were related to tumor stage(P=0.001), but not to gender(P=0.468) and age(P=1.000) of patients. Conclusions: The study shows a high concordance of KRAS, NRAS, BRAF and PIK3CA gene mutations in plasma against mutation status in tumor tissue. In colorectal cancer, tumor tissue remains the best specimen for gene detection. However, patients from tumor tissue specimens cannot be obtained, especially those with advanced metastases, plasma can be used instead of tissue to detect the mutation status of KRAS, NRAS, BRAF and PIK3CA to guide targeted therapy.

Progress in the application of tumor DNA in the diagnosis and treatment of esophageal cancer / 国际外科学杂志

With the development of precision medicine in the field of tumor,thanks to the latest screening technology,the demand for real-time monitoring of tumor is increasingly high.Traditional tissue biopsy is not suitable for repeated due to clinical problems such as puncture clinical risk and tumor heterogeneity.Ultrasound,endoscopy and other imaging examinations are highly subjective,and it is difficult to detect small lesions,and increasingly unable to meet the requirements of real-time monitoring.However,circulating tumor DNA,with its advantages of simple sample acquisition,small trauma,repeatability and real-time monitoring efficacy,has an important application prospect in tumor diagnosis and treatment.Based on the latest reports at home and abroad,this paper reviews the research progress of circulating tumor DNA in the early diagnosis,treatment and prognosis of esophageal cancer.

Combined detection of KRAS, NRAS, BRAF and PIK3CA mutations in the plasma and tumor tissues of colorectal cancer patients / 中华病理学杂志

Objective@#To analyze the concordance of KRAS, NRAS, BRAF and PIK3CA gene mutations detected in plasma and matched tumor tissues in colorectal cancer patients, in order to provide good evidences to support plasma could be a potential surrogate of tumor tissue for gene mutation test.@*Methods@#One hundred and seventy-five cases of colorectal cancer were collected at the First Hospital of Jilin University, from October 2016 to October 2017.There were 101 males and 74 females, their ages ranged from 28 to 85 years,with median age of 59 years. The KRAS, NRAS, BRAF and PIK3CA gene mutations in the plasma and paired tumor specimens of all patients were detected by next generation sequencing.@*Results@#The results of tissue samples test were gold standard. Comparison of the four genes showed that concordance rates between plasma and tissue samples were 81.1%(Kappa=0.543), 99.4%(Kappa=0.886), 99.4% (Kappa=0.886) and 97.7%(Kappa=0.714) respectively for KRAS, NRAS, BRAF and PIK3CA. The plasma detection rates of these genes were related to tumor stage(P=0.001), but not to gender(P=0.468) and age(P=1.000) of patients.@*Conclusions@#The study shows a high concordance of KRAS, NRAS, BRAF and PIK3CA gene mutations in plasma against mutation status in tumor tissue. In colorectal cancer, tumor tissue remains the best specimen for gene detection. However, patients from tumor tissue specimens cannot be obtained, especially those with advanced metastases, plasma can be used instead of tissue to detect the mutation status of KRAS, NRAS, BRAF and PIK3CA to guide targeted therapy.

[Detection of circulating tumor DNA in epidermal growth factor receptor-TKI relapsed non-small cell lung cancer patients using next-generation sequencing and an analysis of the resistant mechanisms].

Objective: Next-generation sequencing (NGS) was performed on circulating tumor DNA (ctDNA) samples from tyrosine kinase inhibitor (TKI)-naïve non-small cell lung cancers (NSCLC) and TKI-relapsed NSCLC to investigate the clinical value. Methods: A total of 381 plasma samples from patients who were diagnosed with lung cancer in Cancer Hospital Chinese Academy of Medical Sciences from March 2017 to May 2018 were enrolled in the study. NGS was performed using a custom-designed panel that covers 10 lung cancer-related driven genes. Paired plasma-tissue samples from 39 patients were collected to analyses the sensitivity and specificity of detecting driver gene mutations using ctDNA. NGS was also performed on plasma samples from TKI-relapsed patients to identify TKI resistance mechanisms. Results: Thirty-nine plasma samples collected from 39 NSCLC patients (including 21 female and 18 male) with corresponding tissue biopsies were analyzed for the sensitivity and specificity. The average age was 56 years (range 29 to 82 years). A high concordance of 84.62% (33/39) was observed between ctDNA and tissue biopsies. Compared with tissue biopsies, NGS sensitivity for ctDNA was 82.14% and specificity was 90.91%.Among these 39 patients, 34 were advanced stage patients (III-IV stage). The concordance, sensitivity, and specificity for ctDNA among the advanced stage patients were 88.24% (30/34), 86.36% (29/34) and 91.67% (31/34), respectively. Among the 381 plasma samples [including 231 TKI-naïve patients and 150 epithelial growth factor receptor(EGFR)-TKI relapsed patients], EGFR mutation was the most common driver gene among the 221 TKI-naïve lung adenocarcinoma patients (32.58%, 72/221). For 133 patients who progressed after first-generation EGFR-TKI, T790M was found to be the most frequent resistant mechanism (39.10%, 52/133), as well as bypass activation (3.01%, 4/133; such as MET amplification and ERBB2 amplification). Among those first-generation EGFR-TKI relapsed patients with EGFR sensitive mutations, T790M was detected in 53.06% (52/98). For the 17 patients who progressed after third-generation EGFR-TKI, C797S was found to be the most common resistant mechanism (4/17). Conclusions: The concordance, sensitivity and specificity between ctDNA and tissue biopsies are acceptable. ctDNA analysis provides valuable information for lung cancer patients' targeted treatment, especially for patients not fitted for biopsies.

Estudio de mutaciones en los genes IDH1 e IDH2 en una muestra de gliomas de población colombiana / Study of mutations in IDH1 and IDH2 genes in a sample of gliomas from Colombian population

Resumen Introducción. Los gliomas son los tumores primarios más comunes del sistema nervioso central y se clasifican de I a IV según su grado de malignidad. En recientes investigaciones se ha encontrado que su aparición está relacionada con mutaciones en el exón 4 de los genes que codifican las deshidrogenasas de isocitrato 1 y 2 (IDH1: codón 132; IDH2: codón 172). Objetivo. Determinar la frecuencia de mutaciones en los genes IDH1 e IDH2 en una muestra de gliomas de pacientes colombianos. Materiales y métodos. La extracción de ADN se hizo a partir de tejido tumoral. El exón 4 de los genes IDH1 e IDH2 se amplificó mediante PCR utilizando iniciadores específicos y, posteriormente, se secuenciaron. Para la determinación de las mutaciones, se emplearon los programas 4Peaksy MAFFT. Resultados. Se determinó la presencia de mutaciones en el gen IDH1 en el 34 % de las muestras, con predominio de la mutación no sinónima R132H. En el 7,5 % de los casos se detectaron mutaciones en el gen IDH2, principalmente las mutaciones no sinónimas R172K y R172W. Conclusiones. La frecuencia de mutaciones en los genes IDH1 e IDH2 en la muestra fue similar a la reportada en otros estudios. El análisis de estas mutaciones puede ser importante como factor pronóstico y para su uso como potenciales blancos terapéuticos en gliomas.

Abstract Introduction: Gliomas are the most common primary tumors of the central nervous system and, according to their malignancy, they are graded from I to IV. Recent studies have found that there is an association between gliomas and mutations in exon 4 of genes that codify for isocitrate dehydrogenases 1 and 2 (IDH1: codon 132; IDH2: codon 172). Objective: To establish the frequency of mutations in IDH1 and IDH2 in a sample of gliomas from Colombian population. Materials and methods: DNA was extracted from tumor tissue. The exon 4 of IDH1 and IDH2 was amplified by PCR using specific primers and subsequently sequenced. Mutations were determined using the 4Peaks MAFFT programs. Results: We found mutations in the IDH1 gene in 34% of the glioma samples, with a predominance of the nonsynonymous mutation R132H. Mutations in the IDH2 gene were found in 7.5% of cases, with a predominance of the nonsynonymous R172K and R172W mutations. Conclusions: The frequency of mutations in the IDH1 and IDH2 genes in the sample was similar to that reported in other studies. The analysis of these mutations may be important to establish prognostic factors and for the development of future therapeutic targets in gliomas.

[Current situation and prospect of breast cancer liquid biopsy].

Liquid biopsy is a diagnostic approach by analyzing body fluid samples. Peripheral blood is the most common sample. Urine, saliva, pleural effusion and ascites are also used. Now liquid biopsy is mainly used in the area of neoplasm diagnosis and treatment. Compared with traditional tissue biopsy, liquid biopsy is minimally invasive, convenient to sample and easy to repeat. Liquid biopsy mainly includes circulating tumor cells and circulating tumor DNA (ctDNA) detection. Detection of ctDNA requires sensitive and accurate methods. The progression of next-generation sequencing (NGS) and digital PCR promote the process of studies in ctDNA. In 2016, Nature published the result of whole-genome sequencing study of breast cancer. The study found 1 628 mutations of 93 protein-coding genes which may be driver mutations of breast cancer. The result of this study provided a new platform for breast cancer ctDNA studies. In recent years, there were many studies using ctDNA detection to monitor therapeutic effect and guide treatment. NGS is a promising technique in accessing genetic information and guiding targeted therapy. It must be emphasized that ctDNA detection using NGS is still at research stage. It is important to standardize ctDNA detection technique and perform prospective clinical researches. The time is not ripe for using ctDNA detection to guide large-scale breast cancer clinical practice at present.

Clinical significance of colposcopy combined with DNA quantitative analysis for cervical cancer and precancerous lesions / 中国医师杂志

Objective To explore the clinical value of DNA quantitative analysis combined with colposcopy in the diagnosis of cervical cancer and precancerous lesions.Methods From January 2015 to January 2017, 500 women with sexual history were enrolled for obstetrics and gynecology.The sensitivity, specificity, and accuracy of DNA quantitative analysis, colposcopy, and the combination of them were evaluated by the pathological examination.Results The DNA quantitative analysis showed that the sensitivity of cervical lesions was 73.75％, the specificity was 94.05％,the positive predictive value was70.24％, and the accuracy rate was 90.8％.Colposcopy showed that the sensitivity of cervical lesions was 82.5％, specificity was 91.43％, positive predictive value was 64.71％, and the accuracy rate was 90.0％.When the two were used together, the sensitivity was 87.5％, the specificity was 95.71％, and the highest accuracy was 94.4％.When three methods were compared together, the differences among the specificity and the accuracy were statistically significant (P ＜ 0.05).For any pairwise comparison, the accuracy of the combined examination was better than that of DNA quantitative analysis and colposcopy (P ＜ 0.05).The specificity of combined examination was significantly better than that of colposcopy (P ＜ 0.05).The sensitivity of combined examination was better than that of DNA quantitative analysis (P ＜ 0.05).Conclusions DNA quantitative analysis combined with colposcopy screening has a higher sensitivity, specificity and accuracy, and it has the best diagnostic value for screening of cervical cancer and precancerous lesions.

Current situation and prospect of breast cancer liquid biopsy / 中华外科杂志

Liquid biopsy is a diagnostic approach by analyzing body fluid samples. Peripheral blood is the most common sample. Urine, saliva, pleural effusion and ascites are also used. Now liquid biopsy is mainly used in the area of neoplasm diagnosis and treatment. Compared with traditional tissue biopsy, liquid biopsy is minimally invasive, convenient to sample and easy to repeat. Liquid biopsy mainly includes circulating tumor cells and circulating tumor DNA (ctDNA) detection. Detection of ctDNA requires sensitive and accurate methods. The progression of next-generation sequencing (NGS) and digital PCR promote the process of studies in ctDNA. In 2016, Nature published the result of whole-genome sequencing study of breast cancer. The study found 1 628 mutations of 93 protein-coding genes which may be driver mutations of breast cancer. The result of this study provided a new platform for breast cancer ctDNA studies. In recent years, there were many studies using ctDNA detection to monitor therapeutic effect and guide treatment. NGS is a promising technique in accessing genetic information and guiding targeted therapy. It must be emphasized that ctDNA detection using NGS is still at research stage. It is important to standardize ctDNA detection technique and perform prospective clinical researches. The time is not ripe for using ctDNA detection to guide large-scale breast cancer clinical practice at present.

Advances of liquid biopsy in the diagnosis and treatment of tumor / 国际肿瘤学杂志

Liquid biopsy mainly focuses on tumor diagnosis,metastasis monitoring,individualized treatment monitoring,curative effect evaluation and prognostic judgment.The main targets include circulating tumor cells,circulating tumor DNA and exosomes.At present,the liquid biopsy target has been used in the clinical monitoring of some tumors,and has good clinical results,but there are still many cha-llenges.

Progress of circulating tumor DNA detection in cancer / 中国基层医药

Peripheral blood circulating tumor DNA(ctDNA) is a kind of DNA that is released into the blood circulation system after the tumor cell somatic cell DNA is exfoliated or when the cell apoptosis is released.ctDNA is a characteristic tumor biomarker, known as " liquid biopsy" . It can reflect the invasion and metastasis of the tumor, and can monitor the effect and prognosis of the tumor.The current research is mainly focused on relatively mature breast cancer, lung cancer and other diseases.In this study, the development of ctDNA inspection technology and its current research status at home and abroad are reviewed.

Detection of circulating tumor DNA in epidermal growth factor receptor-TKI relapsed non-small cell lung cancer patients using next-generation sequencing and an analysis of the resistant mechanisms / 中华病理学杂志

Objective@#Next-generation sequencing (NGS) was performed on circulating tumor DNA (ctDNA) samples from tyrosine kinase inhibitor (TKI)-naïve non-small cell lung cancers (NSCLC) and TKI-relapsed NSCLC to investigate the clinical value.@*Methods@#A total of 381 plasma samples from patients who were diagnosed with lung cancer in Cancer Hospital Chinese Academy of Medical Sciences from March 2017 to May 2018 were enrolled in the study. NGS was performed using a custom-designed panel that covers 10 lung cancer-related driven genes. Paired plasma-tissue samples from 39 patients were collected to analyses the sensitivity and specificity of detecting driver gene mutations using ctDNA. NGS was also performed on plasma samples from TKI-relapsed patients to identify TKI resistance mechanisms.@*Results@#Thirty-nine plasma samples collected from 39 NSCLC patients (including 21 female and 18 male) with corresponding tissue biopsies were analyzed for the sensitivity and specificity. The average age was 56 years (range 29 to 82 years). A high concordance of 84.62% (33/39) was observed between ctDNA and tissue biopsies. Compared with tissue biopsies, NGS sensitivity for ctDNA was 82.14% and specificity was 90.91%.Among these 39 patients, 34 were advanced stage patients (III-IV stage). The concordance, sensitivity, and specificity for ctDNA among the advanced stage patients were 88.24% (30/34), 86.36% (29/34) and 91.67% (31/34), respectively. Among the 381 plasma samples [including 231 TKI-naïve patients and 150 epithelial growth factor receptor(EGFR)-TKI relapsed patients], EGFR mutation was the most common driver gene among the 221 TKI-naïve lung adenocarcinoma patients (32.58%, 72/221). For 133 patients who progressed after first-generation EGFR-TKI, T790M was found to be the most frequent resistant mechanism (39.10%, 52/133), as well as bypass activation (3.01%, 4/133; such as MET amplification and ERBB2 amplification). Among those first-generation EGFR-TKI relapsed patients with EGFR sensitive mutations, T790M was detected in 53.06% (52/98). For the 17 patients who progressed after third-generation EGFR-TKI, C797S was found to be the most common resistant mechanism (4/17).@*Conclusions@#The concordance, sensitivity and specificity between ctDNA and tissue biopsies are acceptable. ctDNA analysis provides valuable information for lung cancer patients′ targeted treatment, especially for patients not fitted for biopsies.

[Exploratory study of circulating tumor DNA detection in early breast cancer: an analysis of 75 next-generation sequencing results].

Objective: To explore the utility of circulating tumor DNA detection in early breast cancer by using next-generation sequencing. Methods: This exploratory study of circulating tumor DNA detection is for early invasive breast cancer patients treated in Breast Disease Center, Peking University First Hospital from December 2015 to July 2016. Plasma samples were collected and were used to isolate plasma cell-free DNA.Exons or hotspots of 247 cancer related genes were sequenced by next-generation sequencing. Mutations and their correlation with clinic-pathological factors were analyzed. The correlation between mutations and clinic-pathological factors was evaluated by χ(2) test or Fisher's exact test. Results: Seventy-five patients were enrolled in this study. All patients were female and aged from 31 to 88 years with median age of 58 years. All patients' clinic-pathological records were complete. Sixty-four mutations in 18 genes (ALK, BCR, ERBB2, ROS1, PDGFRA, EGFR, FGFR2, CYP1B1, CALR, CASP7, BRAF, FGFR1, FGFR3, MET, NRAS, PTEN, KIT, SOD2) were detected in 47 (62.7%) among all 75 patients.Exons were captured in 10 genes, and mutations in 2 of 3 genes analyzed were clustered. Gene mutations were not correlated with menopausal status, histological type, primary tumor (T), regional lymph nodes (N), TNM stage, histological grade, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, Ki-67 and molecular subtype (all P>0.05). Conclusion: Circulating tumor DNA sequencing by next-generation sequencing was useful for detecting breast cancer-related mutations.

[The progression of tumor liquid biopsy and its applications in precision medicine].

Malignant tumor is the most heterogeneous human disease, and it has been gradually reached the consensus in clinical oncology that the personalized treatment of tumor patients should be directed by molecular diagnostics. However, the ever-changing characteristic of tumor in heterogeneity and the fact that tissue samples are usually unavailable highlight the function and significant of liquid biopsy. The material that could be used in liquid biopsy are mainly the circulating tumor DNA, circulating tumor cells and extracellular vesicles, which though have their own advantages and disadvantages, but could complement to each other, thus accurately and comprehensively reflecting the characteristic of the tumor and gave the best direction for patient's individualized therapy. This article reviewed the recent advances of liquid biopsy and explained its importance in tumor precision medicine.

Genetic Biomarker Prevalence Is Similar in Fecal Immunochemical Test Positive and Negative Colorectal Cancer Tissue.

BACKGROUND: Fecal immunochemical test (FIT) screening detects most asymptomatic colorectal cancers. Combining FIT screening with stool-based genetic biomarkers increases sensitivity for cancer, but whether DNA biomarkers (biomarkers) differ for cancers detected versus missed by FIT screening has not been evaluated in a community-based population. AIMS: To evaluate tissue biomarkers among Kaiser Permanente Northern California patients diagnosed with colorectal cancer within 2 years after FIT screening. METHODS: FIT-negative and FIT-positive colorectal cancer patients 50-77 years of age were matched on age, sex, and cancer stage. Adequate DNA was isolated from paraffin-embedded specimens in 210 FIT-negative and 211 FIT-positive patients. Quantitative allele-specific real-time target and signal amplification assays were performed for 7 K-ras mutations and 10 aberrantly methylated DNA biomarkers (NDRG4, BMP3, SFMBT2_895, SFMBT2_896, SFMBT2_897, CHST2_7890, PDGFD, VAV3, DTX1, CHST2_7889). RESULTS: One or more biomarkers were found in 414 of 421 CRCs (98.3%). Biomarker expression was not associated with FIT status, with the exception of higher SFMBT2_897 expression in FIT-negative (194 of 210; 92.4%) than in FIT-positive cancers (180 of 211; 85.3%; p = 0.02). There were no consistent differences in biomarker expression by FIT status within age, sex, stage, and cancer location subgroups. CONCLUSIONS: The biomarkers of a currently in-use multi-target stool DNA test (K-ras, NDRG4, and BMP3) and eight newly characterized methylated biomarkers were commonly expressed in tumor tissue specimens, independent of FIT result. Additional study using stool-based testing with these new biomarkers will allow assessment of sensitivity, specificity, and clinical utility.

Application of liquid biopsy in the diagnosis and treatment of colorectal cancer / 中华检验医学杂志

Liquid biopsy plays an important role in the process of precision medical treatment.Its clinical value in the diagnosis and treatment of various diseases has being constantly proved.Colorectal cancer with high incidence begins subtly.The applicaiton of efficient early screening and diagnostic methods can effectively reduce the disease damage,and the implementation of precise post-operative and medication monitoring as the guidance for therapeutic strategy is helpful to improve the prognosis of patients.We should seize the opportunity to promote the transformation of research findings into the clinical application of colorectal cancer.Clinicians,technicians and regulators should face up and work together to overcome the challenges met during the process of clinical liquid biopsy.