Circulating tumor microemboli (CTM) and vimentin+ circulating tumor cells (CTCs) detected by a size-based platform predict worse prognosis in advanced colorectal cancer patients during chemotherapy

Abstract

BackgroundCirculating tumor cells (CTCs) detected in peripheral blood (PB) of cancer patients can be identified as isolated CTCs and circulating tumor microemboli (CTM). This study aimed to evaluate the prognostic value of CTM detection and CTC phenotype in advanced colorectal cancer (CRC) patients during chemotherapy.MethodsA size-based platform for CTC isolation was applied. PB samples (5 ml) from 98 advanced CRC patients during 2–6 cycles chemotherapy were collected for CTC detection, and CTC count was correlated to patient’s clinicopathological characteristics and clinical outcome. And CTC phenotype was measured by immunofluorescent staining and evaluate the predictive significance on survival in 32 CTCs-positive patients with advanced CRC.ResultsForty-eight of 98 patients were CTCs-positive, including 18 CTM-positive patients, and CTC detection was positively correlated with lymphatic invasion (P = 0.049), TNM stage (P = 0.023), and serum CEA level (P = 0.014). Moreover, Kaplan–Meier survival and Cox regression analyses revealed that the presence of CTCs was an independent factor for poor PFS and OS (P < 0.05) in advanced CRC patients during chemotherapy, and CTM-positive patients had shooter survival than isolated CTCs-positive patients (P < 0.05). Furthermore, patients with vimentin+ isolated CTCs/CTM had shorter PFS and OS compared with CK+ CTCs (P < 0.05).ConclusionsThis study provided evidence that the presence of CTCs was positively correlated with poor prognosis, and furthermore, CTM and vimentin+ CTCs predicted poorer survival, which indicated that CTM and vimentin+ CTCs detected by a sensitive platform could be used to improve prognostic value of CTCs in advanced CRC patients under treatment.

Challenges and unanswered questions for the next decade of circulating tumour cell research in lung cancer

“…Reports of tumour cell clusters or CTM in the blood stream of patients with lung, colon, kidney and prostate cancer (16,(128)(129)(130) have indicated that inclusion within a CTM may provide protection for CTCs particularly since the presence of CTMs is linked with poor prognosis (16,131). Circulating tumour emboli have been defined as groups of tumour cells either alone or associated with fibroblasts (132), leukocytes (133,134), endothelial cells (135)(136)(137) or platelets (138)(139)(140).…”

Liquid biopsy - emergence of a new era in personalized cancer care

“…As CTCs differ in size from other blood components, size-based filtration systems have been frequently used by numerous authors to enrich them [108]. Generally, the filtration system consists of a filtration tube containing the membrane, a manifold vacuum plate with valve settings, a vacuum manifold and a vacuum pump [109][110][111]. Following filtration, CTCs can be stained by standard immuhistochemistry techniques to identify specific proteins or nucleic acid can be extracted and analyzed by ddPCR or NGS to identify mutations [107,[112][113][114].…”

The functions of circulating tumor cells in early diagnosis and surveillance during cancer advancement

“…[4] Tumor cells lose their cell-to-cell adhesion and undergo epithelial-mesenchymal transition in order to enter blood circulation. [5] It is well known that cancers detected at an advanced stage remain largely untreatable.…”