Abstract
With this Letter to the Editor, Franses and Ting respond to questions about their recently published article on improved detection of circulating epithelial cells in patients with intraductal papillary mucinous neoplasms.
We appreciate the interest shown by Dr. Go Yoshida in his letter to the editor regarding our publication “Improved Detection of Circulating Epithelial Cells in Patients with Intraductal Papillary Mucinous Neoplasms” [1], [2]. Specifically, he asked (a) for an explanation of the heterogeneity of MUC RNA expression in the circulating epithelial cells (CEC) derived from patients with intraductal papillary mucinous neoplasms (IPMNs) and (b) why MUC17 RNA sequencing data were shown in two separate rows of the heatmap.
The first issue regarding the heterogeneity of mucin RNA‐sequencing counts in our data (and particularly within the low‐risk “IPMN1” groups) has multiple potential explanations. As we demonstrated in Table 1 and Figure 2B, 2D of the publication, the quantities of circulating cells purified from the blood of patients harboring either IPMNs or pancreatic ductal adenocarcinoma (PDAC) using the CTC‐iChip (Fig. 1B of the publication) were highly variable. Such variability has been noted in our previous work [3], [4], [5], [6] as well as in work by other groups who study circulating tumor cells (CTCs) [7], [8]. Therefore, the number of circulating epithelial cells—within a background of “contaminating” leukocytes—can appreciably impact an RNA sequencing detection approach.
In addition, there are plausible mechanisms from which biological heterogeneity in mucin expression can arise. Indeed, we showed in 2014 [3] via single‐cell RNA sequencing of murine and human PDAC CTCs that there exists significant variability in epithelial markers in CTCs, implying varying degrees of “partial” epithelial‐to‐mesenchymal transition within individual PDAC CTCs. We expect similar biological variability to occur in CECs released from IPMNs.
The second issue is due to a typo. The MUC genes, in order, should be MUC3A, MUC6, MUC12, MUC16, and MUC17 (not MUC3A, MUC6, MUC12, MUC17, and MUC17 as previously shown). We have corrected this issue in a revised Figure 2.
Figure 1.
See the related letter “Regarding “Improved Detection of Circulating Epithelial Cells in Patients with Intraductal Papillary Mucinous Neoplasms”” by Go J. Yoshida on page e119 of this issue.
Disclosures
The authors indicated no financial relationships.
References
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