Detection of CTCs in portal vein was associated with intrahepatic metastases and prognosis in patients with advanced pancreatic cancer

Xiaoyu Liu, Changyu Li, Junhao Li, Tianzhu Yu, Guofeng Zhou, Jiemin Cheng, Guoping Li, Yang Zhou, Wenhui Lou, Xiaolin Wang, Gaoquan Gong, Lingxiao Liu, Yi Chen, Xiaoyu Liu, Changyu Li, Junhao Li, Tianzhu Yu, Guofeng Zhou, Jiemin Cheng, Guoping Li, Yang Zhou, Wenhui Lou, Xiaolin Wang, Gaoquan Gong, Lingxiao Liu, Yi Chen

Abstract

Pancreatic cancer is amongst the most lethal malignancies with increasing incidence and mortality worldwide. Distant metastases, especially intrahepatic metastases, is the leading cause of death for pancreatic cancer. Circulating tumor cells (CTCs) are neoplastic cells released from the primary tumor into circulation, and play critical roles in metastases of various types of cancers. Though clinical studies showed that detection of CTCs in peripheral circulation was associated with worse prognosis in patients with breast cancer and hepatocellular carcinoma, detection CTCs in peripheral blood of pancreatic cancer was still challenging due to hepatic filtration and technical limitations. Previous studies have demonstrated that CTCs could be detected in portal vein circulation in patients with pancreaticobiliary carcinoma. In the present study, taking advantage of ultrasonography-guided transhepatic puncture, we analysis CTCs in portal vein blood obtained from patients with advanced pancreatic cancer. CTCs were detected in all 29-portal vein blood of samples, and absolute numbers of circulating pancreatic cancer cells in portal vein was significantly higher than that in peripheral circulation. Furthermore, we found that CTC counts in portal vein was highly associated with intrahepatic metastases and indicated poorer prognosis in patients with advanced pancreatic cancer. Short-term expansion and in vitro drug sensitivity assay showed that CTCs derived from portal vein blood were highly resistant to several chemotherapy regimens. In summary, detection of CTCs in portal vein could be a powerful tool to stratify the risk of intrahepatic metastases of pancreatic cancer, and provided new insight into the biological feature of pancreatic cancer metastases and drug resistance.

Keywords: circulating tumor cells; intrahepatic metastases; pancreatic cancer; portal vein.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Ultrasonography-guided transhepatic puncture. (A) Identification of the portal vein under the ultrasonography guidance. (B) Transhepatic puncture of the portal vein using the 21 gauge needle.
Figure 2
Figure 2
(A) Detection of CTCs in peripheral blood and (B) portal vein blood in patients with advanced pancreatic cancer. White arrows indicate the CK19 or EpCAM positive CTCs. (C) CTCs clusters derived from portal vein blood. (D) CTCs clusters are significantly higher in portal vein in patients with advanced pancreatic cancer. (E) Portal vein CTCs counts was significantly higher in patients with intrahepatic metastases.
Figure 3
Figure 3
Overall survival was significant shorter in patients with portal vein CTCs over 150 per 7.5 ml. The CTC low groups represented patients with portal vein CTC counts

Figure 4

Drug sensitivity test of portal…

Figure 4

Drug sensitivity test of portal vein CTCs. (A) Drug sensitivity test of case…

Figure 4
Drug sensitivity test of portal vein CTCs.(A) Drug sensitivity test of case CTC15, CTC17, CTC22,CTC28 and CTC 29 using clinical regimens.(B) Portal Vein CTCs were collected twice during the treatment of case CTC12. (C,D) CTCs derived from case CTC12 was highly resistant to gemcitabine, 5-FU and other clinical regimens, but was sensitive to deltarasin.
Figure 4
Figure 4
Drug sensitivity test of portal vein CTCs.(A) Drug sensitivity test of case CTC15, CTC17, CTC22,CTC28 and CTC 29 using clinical regimens.(B) Portal Vein CTCs were collected twice during the treatment of case CTC12. (C,D) CTCs derived from case CTC12 was highly resistant to gemcitabine, 5-FU and other clinical regimens, but was sensitive to deltarasin.

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