BACKGROUNDRecent studies suggest that circulating DNA may be a potential tumor marker for lung cancer, but most of these studies are conducted between healthy controls and lung cancer patients, with few or no benign lung disease patients included. The objective of this study was to evaluate the performance of plasma DNA quantification in discriminating lung cancer from the healthy and benign lung disease.

METHODSPlasma DNA was extracted with a QIAamp DNA Blood Midi kit and quantified by a PicoGreen dsDNA quantitation kit in 44 healthy individuals, 36 benign lung disease patients and 67 lung cancer patients. Discrimination power was evaluated by the receiver operating characteristic curve.

RESULTSPlasma DNA values were significantly increased in lung cancer patients, especially in those with metastases, and in benign lung disease patients compared with that in the healthy individuals (P < 0.001, respectively). The values in lung cancer patients were significantly increased compared with that in the benign lung disease patients (P < 0.001). The area under the curve was 0.96 [95% confidence interval (CI) 0.92 - 0.99] for the healthy versus lung cancer, 0.73 (95% CI 0.64 - 0.83) for lung cancer versus benign lung disease, and 0.86 (95% CI 0.80 - 0.91) for lung cancer versus the healthy and benign lung disease.

CONCLUSIONSPlasma DNA quantification has a strong power to discriminate lung cancer from the healthy and from the healthy and benign lung disease, less power to discriminate lung cancer from benign lung disease. Plasma DNA quantification may be useful as a screening tool for lung cancer.

DNA ; blood ; Humans ; Lung Neoplasms ; blood ; diagnosis ; pathology ; Neoplasm Staging

Biomarkers, Tumor ; blood ; DNA, Neoplasm ; blood ; Humans ; MicroRNAs ; blood ; Molecular Diagnostic Techniques ; Neoplasms ; blood ; diagnosis ; Nucleic Acids ; blood

Circulating tumor cells (CTCs) are tumor cells that are separated from the primary site or metastatic lesion and disseminate in blood circulation. CTCs are considered to be part of the long process of cancer metastasis. As a 'liquid biopsy', CTC molecular examination and investigation of single cancer cells create an important opportunity for providing an understanding of cancer biology and the process of metastasis. In the last decade, we have seen dramatic development in defining the role of CTCs in lung cancer in terms of diagnosis, genomic alteration determination, treatment response and, finally, prognosis prediction. The aims of this review are to understand the basic biology and to review methods of detection of CTCs that apply to the various types of solid tumor. Furthermore, we explored clinical applications, including treatment monitoring to anticipate therapy resistance as well as biomarker analysis, in the context of lung cancer. We also explored the potential use of cell-free circulating tumor DNA (ctDNA) in the genomic alteration analysis of lung cancer.
Biology ; Blood Circulation ; Diagnosis ; DNA ; DNA, Neoplasm ; Lung Neoplasms ; Lung ; Methods ; Neoplasm Metastasis ; Neoplastic Cells, Circulating ; Prognosis

Molecular techniques can be very useful in detecting a patient's tumor to guide treatment decisions is increasingly been applied in the care and management of cancer patients. Circulating tumor DNA (ctDNA) containing mutations can be identified in the plasma of cancer patients during the course of the disease. As a non-invasive "liquid biopsies",ctDNA is a potential surrogate for the entire tumor genome. The use of ctDNA might help to determine the disease prognosis,monitor disease progression,monitor the molecular resistance and monitor the tumor heterogeneity. Future developments will need to provide clinical standards to validate the ctDNA as a clinical biomarker and improve the reproducibility and accuracy,in order to be better exploited for personalized medicine.
DNA, Neoplasm ; blood ; Humans ; Mutation ; Neoplasms ; blood ; diagnosis ; Precision Medicine ; Prognosis ; Reproducibility of Results

OBJECTIVETo detect hypermethylated tumor-specific RASSF1A DNA in the circulation and its significance in ovarian cancers patients.

METHODSMethylation-specific polymerase chain reaction (MSP) was used to study the hypermethylation of RASSF1A in preoperative serum samples from 51 ovarian cancer patients.

RESULTSThe RASSF1A gene was not methylated in peripheral blood samples from 51 normal patients and 51 patients with benign ovarian tumors. Hypermethylation of RASSF1A gene was found in circulating tumor-specific DNA in 43.1% of patients (22 out of 51 cases) with ovarian cancers (P < 0.05). There was no difference in hypermethylation of RASSF1A gene amongst various ovarian cancer subtypes (P < 0.05). On the other hand, hypermethylation of RASSF1A gene was more frequently encountered in stage III and IV than stage I and II tumors (P < 0.05). It was rarely seen in well and moderately differentiated groups, as compared with poorly differentiated group (P < 0.05).

CONCLUSIONSThere is a higher frequency of RASSF1A hypermethylation in circulating tumor-specific DNA of ovarian cancer patients. RASSF1A has been postulated to play an important role as tumor suppressor gene and can be silenced by promoter hypermethylation. This methylation correlates with clinical stage and histopathologic grade. Such observation may carry diagnostic and prognostic implications when assessing ovarian tumors.

Carcinoma, Endometrioid ; blood ; pathology ; Cystadenocarcinoma, Mucinous ; blood ; pathology ; Cystadenocarcinoma, Serous ; blood ; pathology ; DNA Methylation ; Female ; Humans ; Neoplasm Staging ; Ovarian Neoplasms ; blood ; pathology ; Tumor Suppressor Proteins ; blood ; genetics

Prostate cancer is characterized by bone metastases and difficulty of objectively measuring disease burden. In this context, cell-free circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) quantitation and genomic profiling afford the ability to noninvasively and serially monitor the tumor. Recent data suggest that ctDNA and CTC quantitation are prognostic for survival. Indeed, CTC enumeration using the CellSearch^® platform is validated as a prognostic factor and warrants consideration as a stratification factor in randomized trials. Changes in quantities of CTCs using CellSearch also are prognostic and may be employed to detect a signal of activity of new agents. Molecular profiling of both CTCs and ctDNA for androgen receptor (AR) variants has been associated with outcomes in the setting of novel androgen inhibitors. Serial profiling to detect the evolution of new alterations may inform drug development and help develop precision medicine. The costs of these assays and the small quantities in which they are detectable in blood are a limitation, and novel platforms are required to address this challenge. The presence of multiple platforms to assay CTCs and ctDNA also warrants the consideration of a mechanism to allow comparison of data across platforms. Further validation and the continued development and standardization of these promising modalities will facilitate their adoption in the clinic.
Biomarkers, Tumor/blood* ; DNA, Neoplasm/blood* ; Humans ; Male ; Neoplastic Cells, Circulating/immunology* ; Prognosis ; Prostatic Neoplasms/pathology* ; Transcriptome

OBJECTIVETo determine the plasma DNA level and investigate its clinicopathological significance in women with cervical cancers.

METHODSBlood samples were collected from 42 cervical cancer patients, 20 patients with cervical intraepithelial neoplasia grade III (CINIII) and 20 healthy women. The plasma DNA was extracted using a commercial kit and detected by a fluorescentmeter.

RESULTSThe mean plasma DNA level in stage I cervical cancer patients was 12.78-/+5.58 ng/ml, significantly higher than that in CINIII patients (8.10-/+3.06 ng/ml) and normal controls (7.60-/+3.87 ng/ml) (P=0.001). The mean DNA level in stage II-III patients was 17.99-/+7.81 ng/ml, significantly higher than that in stage I patients (P=0.02). No significant difference was found in plasma DNA level between CINIII patients and the normal controls (P>0.05). When the cut-off for diagnosis of cervical cancer was 15.70 ng/ml, the sensitivity, specificity, positive predictive value and negative predictive value were 38.10%, 92.50%, 84.21% and 58.73%, respectively.

CONCLUSIONPlasma DNA level is closely related with malignant transformation and development of cervical cancer, and may become a useful means for differential diagnosis of cervical cancer.

Adult ; Aged ; Carcinoma, Squamous Cell ; blood ; diagnosis ; Cervical Intraepithelial Neoplasia ; blood ; diagnosis ; DNA, Neoplasm ; blood ; Female ; Humans ; Middle Aged ; Sensitivity and Specificity ; Uterine Cervical Neoplasms ; blood ; diagnosis

OBJECTIVETo study the APC and E-cadherin gene promoter hypermethylation as tumor marker and to investigate the correlation of free tumor-related DNA in serum and tumor tissue with clinicopathological parameters. Their feasibility in early diagnosis, predicting therapeutic effect and monitoring recurrence was evaluated.

METHODS84 cases with operated breast cancer were recruited from March 2002 to August 2002 at Beijing Cancer Hospital. Aberrant methylation of E-cadherin and APC genes was detected in tumor tissues, adjacent normal tissues and peripheral blood serum by methylation-specific PCR (MSP). 10 cases with benign breast diseases were selected as control group.

RESULTSThe positive rate of promoter hypermethylation of E-cadherin and APC genes in tumor tissues was 52.4% and 45.2%, in the paired serum was 33.3% and 31.0%, respectively. Aberrant methylation of free DNA in serum presented the same alteration in tumor tissues. E-cadherin and APC hypermethylation in serum and tumor samples significantly correlated each other (E-cadherin P < 0.001; APC P = 0.002). The sensitivity of detection of free DNA methylation of E-cadherin and APC genes in serum was 63.6% and 63.2%, respectively. The specificity was 100% and 95.7%, respectively. There was no correlation for the aberrant methylation in cancer tissues and serum with the clinicopathological parameters of patients including age, tumor staging, tumor size, histological type and receptor. None of the aberrant methylation was found in adjacent normal tissues and control group serum.

CONCLUSIONThe same aberrant methylation in cancer tissues and serum, not correlating with tumor staging, can be detected in about one third of breast cancer patients. The aberrant methylation in serum can disappear after operation. The results imply that this approach may be feasible for early diagnosis, evaluation of therapeutic effects and monitoring recurrence of breast cancers.

Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms ; blood ; genetics ; Cadherins ; blood ; genetics ; CpG Islands ; DNA Methylation ; DNA, Neoplasm ; blood ; genetics ; Female ; Genes, APC ; Genes, Tumor Suppressor ; Humans ; Middle Aged ; Promoter Regions, Genetic ; Sensitivity and Specificity ; Young Adult

DNA, Complementary ; chemistry ; Humans ; Leukocytes ; enzymology ; Lung Neoplasms ; enzymology ; pathology ; Matrix Metalloproteinase 2 ; blood ; genetics ; Matrix Metalloproteinase 9 ; blood ; genetics ; Neoplasm Invasiveness ; Neoplasm Metastasis ; RNA, Messenger ; analysis ; Tissue Inhibitor of Metalloproteinase-1 ; blood ; genetics

BACKGROUND/AIMS: The plasma DNA concentration of patients with cancer is known to be higher than normal controls. Increased DNA concentration and tumor-specific genes in plasma can be used as tumor markers in some cancers. This study was designed to evaluate whether quantification of plasma DNA concentration by using real-time PCR is useful as a tumor marker in the diagnosis of pancreatic cancer. METHODS: Twenty-four patients (M:F=16:8, mean age; 60.5+/-11.5 years) with pancreatic cancer were recruited for this study. Fifteen patients with chronic pancreatitis and fifteen healthy persons were selected as controls (M:F=26:4, 53.5+/-11.2 years). The concentration of plasma DNA was determined by real-time PCR for telomerase reverse transcriptase gene. RESULTS: Plasma DNA concentration in patients with pancreatic cancer (46.4+/-63.2 ng/mL) was higher than that of chronic pancreatitis (p=0.041) and normal controls (p=0.030). The sensitivity and specificity in detecting pancreatic cancer were 75% and 70% respectively when the cut-off value of plasma DNA concentration was set at 46.9 ng/mL. CONCLUSIONS: Plasma DNA concentration in patients with pancreatic cancer was higher than that of controls. However, its sensitivity and specificity is not high enough to be used as a tumor marker for pancreatic cancer.
Adult ; Aged ; DNA, Neoplasm/*blood ; Diagnosis, Differential ; Female ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms/*diagnosis ; Pancreatitis, Chronic/diagnosis ; Polymerase Chain Reaction ; Tumor Markers, Biological/*blood