Dataset Information

Evaluation of circulating tumor cell clusters for pan-cancer noninvasive diagnostic triaging.

ABSTRACT:

Background

Histopathologic examination (HPE) of tumor tissue obtained by invasive biopsy is the standard for cancer diagnosis but is resource-intensive and has been associated with procedural risks. The authors demonstrate that immunocytochemistry (ICC) profiling of circulating ensembles of tumor-associated cells (C-ETACs) can noninvasively provide diagnostic guidance in solid organ cancers.

Methods

The clinical performance of this approach was tested on blood samples from 30,060 individuals, including 9416 individuals with known cancer; 6725 symptomatic individuals with suspected cancer; and 13,919 asymptomatic individuals with no prior diagnosis of cancer. C-ETACs were harvested from peripheral blood and profiled by ICC for organ-specific and subtype-specific markers relevant to the cancer type. ICC profiles were compared with HPE diagnoses to determine concordance.

Results

The presence of malignancy was confirmed by the detection of C-ETACs in 91.8% of the 9416 individuals with previously known cancer. Of the 6725 symptomatic individuals, 6025 were diagnosed with cancer, and 700 were diagnosed with benign conditions; C-ETACs were detected in 92.6% of samples from the 6025 individuals with cancer. In a subset of 3509 samples, ICC profiling of C-ETACs for organ-specific and subtype-specific markers was concordant with HPE findings in 93.1% of cases. C-ETACs were undetectable in 95% of samples from the 700 symptomatic individuals who had benign conditions and in 96.3% of samples from the 13,919 asymptomatic individuals.

Conclusions

C-ETACs were ubiquitous (>90%) in various cancers and provided diagnostically relevant information in the majority (>90%) of cases. This is the first comprehensive report on the feasibility of ICC profiling of C-ETACs to provide pan-cancer diagnostic guidance with accuracy comparable to that of HPE.

SUBMITTER: Gaya A

PROVIDER: S-EPMC7984349 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Evaluation of circulating tumor cell clusters for pan-cancer noninvasive diagnostic triaging.

Gaya Andrew A Crook Timothy T Plowman Nicholas N Ranade Anantbhushan A Limaye Sewanti S Bhatt Amit A Page Raymond R Patil Revati R Fulmali Pradip P Datta Vineet V Kumar Prashant P Patil Darshana D Akolkar Dadasaheb D

Cancer cytopathology 20200930 3

<h4>Background</h4>Histopathologic examination (HPE) of tumor tissue obtained by invasive biopsy is the standard for cancer diagnosis but is resource-intensive and has been associated with procedural risks. The authors demonstrate that immunocytochemistry (ICC) profiling of circulating ensembles of tumor-associated cells (C-ETACs) can noninvasively provide diagnostic guidance in solid organ cancers.<h4>Methods</h4>The clinical performance of this approach was tested on blood samples from 30,060 ...[more]

PMID: 32996712

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Project description:Background: Gastric cancer (GC) remains the third leading cause of cancer death worldwide due to the absence of sensitive and specific biomarkers for its early detection. 5-hydroxymethylcytosine (5hmC)-enriched gene profiles and regions show tissue-specific and tumor specific, and cell-free DNA (cfDNA) 5hmC modification feature sequencing provides a robust tool for gastric cancer detection.Methods: A matched case‒control study design with 50 gastric cancer patients and 50 controls was performed to sequence the 5hmC modification of cfDNA. Significantly differential 5hmC modification genes were identified to construct a gastric cancer diagnostic model. The data set from Gene Expression Omnibus consisted of 61 gastric cancer patients, 90 healthy individuals and 22 benign gastric disease controls was used as an external testing set to test the robustness of the diagnostic model. Results: The vast majority of 5hmC peaks were distributed in the gene body, accounting for more than 90% of the total 5hmC peaks in both the GC and control groups. The diagnostic model was developed based on five different 5hmC modification genes, FBXL7, PDE3A, TPO, SNTG2 and SXBP5. The model could clearly distinguish gastric cancer patients from controls in the training (AUC=0.95, sensitivity=88.6%, specificity=94.3%), validation (AUC=0.87, sensitivity=73.3%, specificity=93.3%) and testing (AUC=0.90, sensitivity=81.9%, specificity=90.2%) sets. The predicted risk scores of the controls were significantly lower than those of GC patients in our own data (P<0.001) or GEO external testing data (P<0.001), but no significant difference was observed between different TNM stage groups (P=0.09 and 0.66). Furthermore, the risk scores of healthy and benign gastric disease controls in the testing set were also not different (P=0.10). Conclusions: The characteristics of 5hmC in cfDNA are specific to GC patients, and the diagnostic model constructed by the 5hmC features of five genes could effectively identify GC patients.

Dataset Information

Evaluation of circulating tumor cell clusters for pan-cancer noninvasive diagnostic triaging.

Background

Methods

Results

Conclusions

Publications

Evaluation of circulating tumor cell clusters for pan-cancer noninvasive diagnostic triaging.

Similar Datasets

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