Research ArticleBioengineering

Cancer Cell Profiling by Barcoding Allows Multiplexed Protein Analysis in Fine-Needle Aspirates

Science Translational Medicine  15 Jan 2014:
Vol. 6, Issue 219, pp. 219ra9
DOI: 10.1126/scitranslmed.3007361

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Fine-Tuning Single Cancer Cell Protein Analysis

Fine-needle aspirates (FNAs) use thin needles to obtain cells from tumor masses. FNAs can give tremendous insight into malignancy, but the number of cells is so small that current technologies for protein analysis, such as immunohistochemistry, are insufficient. To address this technological gap, Ullal and colleagues developed the antibody barcoding with photocleavable DNA (ABCD) platform that allows for simultaneous analysis of many surface proteins on cells from cancer patients.

The authors first isolated cancer cells within the FNAs of patients. These cells were then exposed to a cocktail of 90 antibodies, covering the hallmark processes in cancer (for example, apoptosis and DNA damage), and each containing a unique “barcode”—a single strand of DNA that could be released by light (photocleaved) and quantified using fluorescent complementary probes. After validating protein expression on human cancer cell lines with known protein composition, Ullal et al. moved to FNA samples from patients with lung adenocarcinoma. The protein profiles of 11 single cells taken from one patient showed low correlation with the bulk tumor sample, indicating high intratumor heterogeneity. The authors also noted high intertumor heterogeneity, because six patients with tumors that looked identical under a microscope had different proteomic profiles. By clustering the protein expression results and comparing to the patients’ genetic makeup, the authors suggest that therapies could be better personalized.

The ABCD platform could help researchers to better understand tumor heterogeneity, as well as allow clinicians to personalize therapies and perhaps even track therapeutic response less invasively, as the authors demonstrated in vitro and in four patients taking kinase inhibitors. Technological challenges remain in making this platform validated and ready for the bedside, but successful early demonstrations in patients with lung cancer suggest that larger-scale clinical trials are in the near future.