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Circulating Tumor Cell Count Correlates with Colorectal Neoplasm Progression and Is a Prognostic Marker for Distant Metastasis in Non-Metastatic Patients.

ABSTRACT: Enumeration of circulating tumor cells (CTCs) has been proven as a prognostic marker for metastatic colorectal cancer (m-CRC) patients. However, the currently available techniques for capturing and enumerating CTCs lack of required sensitivity to be applicable as a prognostic marker for non-metastatic patients as CTCs are even more rare. We have developed a microfluidic device utilizing antibody-conjugated non-fouling coating to eliminate nonspecific binding and to promote the multivalent binding of target cells. We then established the correlation of CTC counts and neoplasm progression through applying this platform to capture and enumerate CTCs in 2 mL of peripheral blood from healthy (n = 27), benign (n = 21), non-metastatic (n = 95), and m-CRC (n = 15) patients. The results showed that the CTC counts progressed from 0, 1, 5, to 36. Importantly, after 2-year follow-up on the non-metastatic CRC patients, we found that those who had ≥5 CTCs were 8 times more likely to develop distant metastasis within one year after curable surgery than those who had <5. In conclusion, by employing a sensitive device, CTC counts show good correlation with colorectal neoplasm, thus CTC may be as a simple, independent prognostic marker for the non-metastatic CRC patients who are at high risk of early recurrence.

SUBMITTER: Tsai WS

PROVIDER: S-EPMC4830949 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivePlatelets have been implicated in cancer metastasis and prognosis. No population-based study has been reported as to whether preoperative platelet count directly predicts metastatic recurrence of colorectal cancer (CRC) patients.DesignUsing a well-characterized cohort of 1,513 surgically resected CRC patients, we assessed the predictive roles of preoperative platelet count in overall survival, overall recurrence, as well as locoregional and distant metastatic recurrences.ResultsPatients with clinically high platelet count (≥400 × 10(9)/L) measured within 1 month before surgery had a significantly unfavorable survival (hazard ratio [HR] = 1.66, 95 % confidence interval [CI] 1.34-2.05, P = 2.6 × 10(-6), P(log rank) = 1.1 × 10(-11)) and recurrence (HR = 1.90, 1.24-2.93, P = 0.003, P(log rank) = 0.003). The association of platelet count with recurrence was evident only in patients with metastatic (HR = 2.81, 1.67-4.74, P = 1.1 × 10(-4), P(log rank) = 2.6 × 10(-6)) but not locoregional recurrence (HR = 0.59, 95 % CI 0.21-1.68, P = 0.325, P(log rank) = 0.152). The findings were internally validated through bootstrap resampling (P < 0.01 at 98.6 % of resampling). Consistently, platelet count was significantly higher in deceased than living patients (P < 0.0001) and in patients with metastatic recurrence than locoregional (P = 0.004) or nonrecurrent patients (P < 0.0001). Time-dependent modeling indicated that the increased risks for death and metastasis associated with elevated preoperative platelet counts persisted up to 5 years after surgery.ConclusionOur data demonstrated that clinically high level of preoperative platelets was an independent predictor of CRC survival and metastasis. As an important component of the routinely tested complete blood count panel, platelet count may be a cost-effective and noninvasive marker for CRC prognosis and a potential intervention target to prevent metastatic recurrence.

Project description:BackgroundMore and more evidence indicated that tumor deposit (TD) was significantly associated with local recurrence, distant metastasis (DM), and poor prognosis for patients with colorectal cancer (CRC). This study aims to explore the main clinical risk factors for the presence of TD in CRC patients with no DM (CRC-NDM) and the prognostic factors for TD-positive patients after surgery.MethodsThe data of patients with CRC-NDM between 2010 and 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. A logistic regression model was used to identify risk factors for TD presence. Fine and Gray's competing-risk model was performed to analyze prognostic factors for TD-positive CRC-NDM patients. A predictive nomogram was constructed using the multivariate logistic regression model. The concordance index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and the calibration were used to evaluate the predictive nomogram. Also, a prognostic nomogram was built based on multivariate competing-risk regression. C-index, the calibration, and decision-curve analysis (DCA) were performed to validate the prognostic model.ResultsThe predictive nomogram to predict the presence of TD had a C-index of 0.785 and AUC of 0.787 and 0.782 in the training and validation sets, respectively. From the competing-risk analysis, chemotherapy (subdistribution hazard ratio (SHR) = 0.542, p < 0.001) can significantly reduce CRC-specific death (CCSD). The prognostic nomogram for the outcome prediction in postoperative CRC-NDM patients with TD had a C-index of 0.727. The 5-year survival of CCSD was 17.16%, 36.20%, and 63.19% in low-, medium-, and high-risk subgroups, respectively (Gray's test, p < 0.001).ConclusionsWe constructed an easily predictive nomogram in identifying the high-risk TD-positive CRC-NDM patients. Besides, a prognostic nomogram was built to help clinicians identify poor-outcome individuals in postoperative CRC-NDM patients with TD. For the high-risk or medium-risk subgroup, additional chemotherapy may be more advantageous for the TD-positive patients rather than radiotherapy.

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Circulating Tumor Cell Count Correlates with Colorectal Neoplasm Progression and Is a Prognostic Marker for Distant Metastasis in Non-Metastatic Patients.

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