Resolving an underrepresented circulating tumor cell population in lung cancer enabled by Hexokinase 2 analysis

Yang, L.; Yan, X.; Chen, J.; Zhan, Q.; Hua, Y.; Xu, S.; Dong, Y.; Li, Z.; Wang, Z.; Zuo, D.; Xue, M.; Tang, Y.; Herschman, H. R.; Lu, S.; Shi, Q.; Wei, W.

doi:10.1101/2020.04.27.064345

bioRxiv · 10.1101/2020.04.27.064345

Resolving an underrepresented circulating tumor cell population in lung cancer enabled by Hexokinase 2 analysis

Yang, L.·Yan, X.·Chen, J.·Zhan, Q.·Hua, Y.·Xu, S.·Dong, Y.·Li, Z.·Wang, Z.·Zuo, D.·Xue, M.·Tang, Y.·Herschman, H. R.·Lu, S.·Shi, Q.·Wei, W.

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Abstract

Unlike other epithelial cancer types, circulating tumor cells (CTCs) are less frequently detected in the peripheral blood of non-small cell lung cancer (NSCLC) patients using epithelial marker-based detection approaches, despite the aggressive nature of NSCLC. Here we demonstrate hexokinase-2 (HK2) as a metabolic function-associated marker for detection of CTCs, with significantly improved detection rates and high specificity, in 33 NSCLC patients. Use of the HK2 marker identified underrepresented cytokeratin-negative (HK2high/CKneg) CTCs present in many blood samples but rarely detected in pleural effusions or cerebrospinal fluids of NSCLC patients. HK2high/CKneg CTCs exhibited smaller sizes but consistent copy number variation profiles compared to CKpos CTCs. Surprisingly, CK expression levels were found to be independent of CTC epithelial-to-mesenchymal transition (EMT) status as measured by single-cell transcriptome profiling, challenging the long-standing association between CK expression and EMT. Our approach improves sensitivity of CTC detection in NSCLC and can potentially resolve a more complete spectrum of CTCs, regardless of their CK expression levels or epithelial traits.

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Yang, L., Yan, X., Chen, J., Zhan, Q., Hua, Y., Xu, S., Dong, Y., Li, Z., Wang, Z., Zuo, D., Xue, M., Tang, Y., Herschman, H. R., Lu, S., Shi, Q., Wei, W.. 2020-04-29. Resolving an underrepresented circulating tumor cell population in lung cancer enabled by Hexokinase 2 analysis. https://doi.org/10.1101/2020.04.27.064345

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