Association of circulating tumor cell-white blood cell clusters with survival outcomes in patients with colorectal cancer after curative intent surgery

Abstract

Background The analysis of circulating tumor cell-associated white blood cell (CTC-WBC) clusters represented the progress in the liquid biopsy of malignant tumors, however, related research in patients with colorectal cancer is still absent. Methods To explore associations between CTC-WBC clusters and the prognosis of these patients, we conducted an independent cohort of 329 colorectal cancer patients after curative intent surgery and pre-operative CTC detection in Nanfang Hospital, Southern Medical University, Guangzhou, China between January 1, 2017, and September 31, 2019. The primary cohort referred to patients with CTC-WBC clusters positive. The control cohort was defined as those with exclusively CTCs positive. CTCs were enriched and distinguished by The CanPatrol™ system (SurExam, China). The Kaplan–Meier curve was used to compare the progressive-free survival (PFS) and overall survival (OS) between two groups. The COX regression model was used to assess the predictive value of CTC-WBC clusters. Results Sixty three patients presented CTC-WBC clusters positive (CTC-WBC group) and 266 patients showed solely CTCs (CTC group). The number of CTCs was significantly different between two groups (P < 0.001) and the rest of clinical characteristics were not markedly associated with the presence of CTC-WBC clusters. Kaplan–Meier curves of PFS and OS exhibited that the CTC-WBC group had significantly shorter PFS (P = 0.011), while not for OS. The multivariate model further suggested that the CTC-WBC clusters (Hazard Ratio = 1.89, 95% Confidence Interval 1.02–3.51, P = 0.042) was an independent predictor for the PFS of in post-operation CRC patients. Conclusion The CTC-WBC cluster is significantly associated with recurrence after operation in CRC patients. This finding facilitates the evaluation of this indicator in tumor progression.

Prognostic value of circulating tumor cells associated with white blood cells in solid cancer: a systematic review and meta-analysis of 1471 patients with solid tumors

“…Prospective studies, as represented by Jansson et al [ 16 ] and Zhu et al [ 20 ], showed a significant association of CTC-WBCs with OS (HR = 11.44, 95% CI: 2.71–48.37, P = 0.001, Table 3 ). The retrospective studies [ 10 , 11 , 18 , 19 ] also demonstrated a notable association with OS (HR = 2.55, 95% CI: 1.78–3.63, P < 0.001, Table 3 ). For disease progression endpoints, the prospective group reported an HR of 1.31 (95% CI: 0.46–3.75, P = 0.609).…”

“…Qiu et al [ 18 ] identified a noteworthy association of CTC-WBCs with OS in GC (HR = 2.553, 95% CI: 1.008–6.465, P = 0.048). Xu et al [ 19 ] observed a similar trend for PFS in CRC (HR = 1.89, 95% CI: 1.02–3.51, P = 0.042), though the OS association was not significant. Additionally, Zhu et al [ 20 ] found that in SCLC, CTC-WBC clusters were a significant prognostic factor for OS both before treatment (HR = 9.3, 95% CI: 1.4–48, P = 0.0079) and after two chemotherapy cycles (HR = 4.4, 95% CI: 1.1–18, P = 0.041), highlighting their consistent prognostic value regardless of treatment stage.…”

“…In two studies [ 10 , 18 ], blood samples were collected from patients after local or systemic therapy. Five other studies [ 11 , 14 , 15 , 17 , 19 ] focused on pretreatment samples. Three studies [ 13 , 16 , 20 ] collected blood samples from patients at multiple time points, allowing for confirmation of the prognostic value of positive results at different stages (Table 1 ).…”

“…To our knowledge, this study constitutes the first pooled analysis evaluating the prognostic significance of CTC-WBCs. Our systematic review and meta-analysis included three prospective [ 15 , 16 , 20 ] and seven retrospective studies [ 10 , 11 , 13 , 14 , 17 – 19 ], involving a total of 1471 patients with seven different types of solid cancer. The main findings of the current study indicate that the presence of CTC-WBCs is significantly associated with worse OS and PFS/DFS/MFS/RFS in patients with solid tumors.…”

“…However, some studies have indicated that preoperative CTC-WBCs do not correlate with progression-free survival (PFS) [ 13 ]. Therefore, to determine the prognostic value of CTC-WBCs and to interpret the results of available studies statistically, we performed this meta-analysis to evaluate the diagnostic accuracy and prognostic value of testing for CTC-WBC clusters in several solid cancers, including hepatocellular carcinoma (HCC) [ 11 , 14 ], renal cell carcinoma (RCC) [ 10 , 13 ], metastatic breast cancer (MBC) [ 15 , 16 ], non-small cell lung cancer (NSCLC) [ 17 ], gastric cancer (GC) [ 18 ], colorectal cancer (CRC) [ 19 ], and small cell lung cancer (SCLC) [ 20 ].…”