Sachin Narayan

All Publications

• Defining A Liquid Biopsy Profile of Circulating Tumor Cells and Oncosomes in Metastatic Colorectal Cancer for Clinical Utility. Cancers Narayan, S., Courcoubetis, G., Mason, J., Naghdloo, A., Kolenčík, D., Patterson, S. D., Kuhn, P., Shishido, S. N. 2022; 14 (19)

  Abstract

  Metastatic colorectal cancer (mCRC) is characterized by its extensive disease heterogeneity, suggesting that individualized analysis could be vital to improving patient outcomes. As a minimally invasive approach, the liquid biopsy has the potential to longitudinally monitor heterogeneous analytes. Current platforms primarily utilize enrichment-based approaches for epithelial-derived circulating tumor cells (CTC), but this subtype is infrequent in the peripheral blood (PB) of mCRC patients, leading to the liquid biopsy's relative disuse in this cancer type. In this study, we evaluated 18 PB samples from 10 mCRC patients using the unbiased high-definition single-cell assay (HDSCA). We first employed a rare-event (Landscape) immunofluorescence (IF) protocol, which captured a heterogenous CTC and oncosome population, the likes of which was not observed across 50 normal donor (ND) samples. Subsequent analysis was conducted using a colorectal-targeted IF protocol to assess the frequency of CDX2-expressing CTCs and oncosomes. A multi-assay clustering analysis isolated morphologically distinct subtypes across the two IF stains, demonstrating the value of applying an unbiased single-cell approach to multiple assays in tandem. Rare-event enumerations at a single timepoint and the variation of these events over time correlated with progression-free survival. This study supports the clinical utility of an unbiased approach to interrogating the liquid biopsy in mCRC, representing the heterogeneity within the CTC classification and warranting the further molecular characterization of the rare-event analytes with clinical promise.

  View details for DOI 10.3390/cancers14194891

  View details for PubMedID 36230811

  View details for PubMedCentralID PMC9563925

• Time delay and evidence profiles forming clinical recommendations of US surgical society guidelines. Surgery Berg, A., Cho, N. Y., Chattopadhyay, K., Narayan, S., Alawa, J., Spain, D. A., Choi, J. 2024: 108916

  Abstract

  Surgical society guidelines facilitate implementation of up-to-date, evidence-based care, but concerns regarding the contemporality and quality of evidence can hinder adherence. We aimed to evaluate the time gap between evidence publication and their inclusion within clinical guidelines-the publication-to-guideline delay-and characterize the quality of evidence within contemporary surgical society guidelines.This cross-sectional study analyzed guidelines published by U.S. surgical societies between 2015 and 2020 and references informing clinical recommendations. The primary outcomes were the publication-to-guideline delay and the quality of evidence supporting clinical recommendations. Differences between societies were analyzed using the Kruskal Wallis and Fisher exact tests. All data were extracted by three reviewers, and inter-rater reliability was assessed using the Kappa coefficient.Fifty-seven guidelines met inclusion criteria; among 6200 cited references, 3892 informed specific clinical recommendations. The median [IQR] publication-to-guideline delay was 9 [5-14] years and ranged across societies between 7 and 11 years. A majority (54%) of evidence informing recommendations comprised retrospective observational studies (54%). Despite only 14% of evidence graded as high-quality, 59% of clinical recommendations were strong. Societies showed statistically significant variations in their proportion of study designs, quality of evidence, and strength of recommendations.U.S. surgical societies have a unique potential to disseminate evidence through guidelines. We found that concerns regarding the contemporality and quality of evidence constituting surgical guidelines may be valid. Societies should critically evaluate procedures for reviewing the timeliness and quality of evidence to ensure guidelines remain up-to-date and reliable.

  View details for DOI 10.1016/j.surg.2024.10.007

  View details for PubMedID 39592333

• Circulating Tumor Cell Kinetics and Morphology from the Liquid Biopsy Predict Disease Progression in Patients with Metastatic Colorectal Cancer Following Resection. Cancers Kolenčík, D., Narayan, S., Thiele, J. A., McKinley, D., Gerdtsson, A. S., Welter, L., Hošek, P., Ostašov, P., Vyčítal, O., Brůha, J., Fiala, O., Šorejs, O., Liška, V., Pitule, P., Kuhn, P., Shishido, S. N. 2022; 14 (3)

  Abstract

  The liquid biopsy has the potential to improve current clinical practice in oncology by providing real-time personalized information about a patient's disease status and response to treatment. In this study, we evaluated 161 peripheral blood (PB) samples that were collected around surgical resection from 47 metastatic colorectal cancer (mCRC) patients using the High-Definition Single Cell Assay (HDSCA) workflow. In conjunction with the standard circulating tumor cell (CTC) enumeration, cellular morphology and kinetics between time-points of collection were considered in the survival analysis. CTCs, CTC-Apoptotic, and CTC clusters were found to indicate poor survival with an increase in cell count from pre-resection to post-resection. This study demonstrates that CTC subcategorization based on morphological differences leads to nuanced results between the subtypes, emphasizing the heterogeneity within the CTC classification. Furthermore, we show that factoring in the time-point of each blood collection is critical, both for its static enumeration and for the change in cell populations between draws. By integrating morphology and time-based analysis alongside standard CTC enumeration, liquid biopsy platforms can provide greater insight into the pathophysiology of mCRC by highlighting the complexity of the disease across a patient's treatment.

  View details for DOI 10.3390/cancers14030642

  View details for PubMedID 35158910

  View details for PubMedCentralID PMC8833610