Dataset Information

A transcriptomic signature that predicts cancer recurrence after hepatectomy in patients with colorectal liver metastases.

ABSTRACT:

Background

Cancer recurrence is an important predictor of survival outcomes in patients with colorectal cancer-associated liver metastasis (CRLM), who undergo radical hepatectomy. Therefore, identification of patients with the greatest risk of recurrence is critical for developing a precision oncology strategy that might include frequent surveillance (in low-risk patients) or a more aggressive treatment approach (in high-risk patients). We performed genome-wide expression profiling, to identify and develop a transcriptomic signature for predicting recurrence in patients with CRLM.

Methods

We analysed a total of 383 patients with CRLM, including 63 patients from a publicly available data set (the NCBI's Gene Expression Omnibus with accession number GSE81423). and 320 patients from whom surgical specimens were collected for independent training (n = 169) and validation (n = 151) of identified biomarkers. Using Cox's proportional hazard regression analysis, we evaluated the clinical significance of the identified gene signature by comparing its performance with several key clinical factors.

Results

We identified a six-gene panel that robustly categorised patients with recurrence in the discovery (area under the curve (AUC) = 0.90). We showed that the panel was a significant predictor of recurrence in the clinical training (AUC = 0.83) and validation cohorts (AUC = 0.81). By combining our panel with key clinical factors, we established a risk-stratification model that emerged as an independent predictor of recurrence (AUC = 0.85; univariate: hazard ratio (HR) = 4.34, 95% confidence interval (CI) = 2.71-6.93, P < 0.001; multivariate: HR = 3.40, 95% CI = 1.76-6.56, P < 0.001). The stratification model revealed recurrence prediction in 89% of high-risk group and non-recurrence in 62% of low-risk group.

Conclusions

We established a novel transcriptomic signature that robustly predicts recurrence, which has significant implications for the management of patients with CRLM.

SUBMITTER: Wada Y

PROVIDER: S-EPMC8860859 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

A transcriptomic signature that predicts cancer recurrence after hepatectomy in patients with colorectal liver metastases.

Wada Yuma Y Shimada Mitsuo M Morine Yuji Y Ikemoto Tetsuya T Saito Yu Y Baba Hideo H Mori Masaki M Goel Ajay A

European journal of cancer (Oxford, England : 1990) 20220114

<h4>Background</h4>Cancer recurrence is an important predictor of survival outcomes in patients with colorectal cancer-associated liver metastasis (CRLM), who undergo radical hepatectomy. Therefore, identification of patients with the greatest risk of recurrence is critical for developing a precision oncology strategy that might include frequent surveillance (in low-risk patients) or a more aggressive treatment approach (in high-risk patients). We performed genome-wide expression profiling, to i ...[more]

PMID: 35042069

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Project description:BackgroundPatients with initially unresectable colorectal cancer liver metastases (IU-CRLM) might benefit from using an effective systemic treatment followed by resection of liver metastases but the curative success rate is quite low. Indeed, nearly one-third of patients exhibit early recurrence within the first 6 months after surgery, and these individuals often have poor overall survival.ObjectivesThis study aims to clarify the application value of serial circulating tumor DNA (ctDNA) analysis in predicting the clinical outcome of IU-CRLM patients following liver metastasectomy.DesignA retrospective study was conducted on a cohort of patients with IU-CRLM between February 2018 and April 2021.MethodsPlasma samples at different time points during CRLM treatment [baseline (BL), preoperation (PRE), postoperation (POST), end-of-treatment (EOT), and progressive disease (PD)] were retrospectively collected from patients with initially unresectable CRLM enrolled at the Sun Yat-sen University Cancer Center. Dynamic changes of SEPTIN 9 (SEPT9) and Neuropeptide Y (NPY) methylated circulating tumor DNA (MetctDNA) levels in serial plasma samples were detected using droplet-digital PCR (ddPCR).ResultsSEPT9 and NPY genes were hypermethylated in colon cancer cell lines and tissues while no difference was observed between primary and metastatic tumors. Patients with MetctDNA positive at POST or EOT had significantly lower recurrence-free survival (RFS) compared to patients with MetctDNA negative at these time points [POST: Hazard ratio (HR) 9.44, 95% confidence interval (CI) 5.15-17.30, p < 0.001; EOT: HR 11.48, 95% CI 3.27-40.31, p < 0.001]. Multivariate analysis demonstrated that POST (OR 33.96, 95% CI 4.03-286.10, p = 0.001) and EOT (OR 18.36, 95% CI 1.14-295.71, p = 0.04) MetctDNA was an independent risk factor for early recurrence. Time-dependent receiver operating characteristic curve (T-ROC) analysis revealed that area under the curve (AUC) value was greatest at the relapse time point of 6 months post-intervention, with POST-AUC and EOT-AUC values of 0.74 (95% CI 0.66-0.81) and 0.73 (95% CI 0.53-0.94), respectively. Serial MetctDNA analysis showed that RFS was significantly lower in patients with no MetctDNA clearance compared with those with MetctDNA clearance (HR 26.05, 95% CI 4.92-137.81, p < 0.001).ConclusionOur study confirmed that serial ctDNA analysis of NPY and SEPT9 gene methylation could effectively predict early recurrence in IU-CRLM patients, especially at POST and EOT.

Project description:BackgroundThe purpose of this study was to determine the optimal definition and elucidate the predictive factors of early recurrence after surgery for colorectal liver metastases (CRLM).MethodsAmong 987 patients who underwent curative surgery for CRLM from 1990 to 2012, 846 with a minimum follow-up period of 24 months were eligible for this study. The minimum p value approach of survival after initial recurrence was used to determine the optimal cutoff for the definition of early recurrence. The predictive factors of early recurrence and prognostic factors of survival were analyzed.ResultsFor 667 patients (79%) who developed recurrence, the optimal cutoff point of early recurrence was determined to be 8 months after surgery. The impact of early recurrence on survival was demonstrated mainly in patients who received preoperative chemotherapy. Among the 691 patients who received preoperative chemotherapy, recurrence was observed in 562 (81%), and survival in patients with early recurrence was significantly worse than in those with late recurrence (5-year survival 18.5% vs. 53.4%, p < .0001). Multivariate logistic analysis identified age ≤57 years (p = .0022), >1 chemotherapy line (p = .03), disease progression during last-line chemotherapy (p = .024), >3 tumors (p = .0014), and carbohydrate antigen 19-9 >60 U/mL (p = .0003) as independent predictors of early recurrence. Salvage surgery for recurrence significantly improved survival, even in patients with early recurrence.ConclusionThe optimal cutoff point of early recurrence was determined to be 8 months. The preoperative prediction of early recurrence is possible and crucial for designing effective perioperative chemotherapy regimens.Implications for practiceIn this study, the optimal cutoff point of early recurrence was determined to be 8 months after surgery based on the minimum p value approach, and its prognostic impact was demonstrated mainly in patients who received preoperative chemotherapy. Five factors, including age, number of preoperative chemotherapy lines, response to last-line chemotherapy, number of tumors, and carbohydrate antigen 19-9 concentrations, were identified as predictors of early recurrence. Salvage surgery for recurrence significantly improved survival, even in patients with early recurrence. For better selection of patients who could truly benefit from surgery and should also receive strong postoperative chemotherapy, the accurate preoperative prediction of early recurrence is crucial.

Project description:BackgroundCarcinoembryonic antigen (CEA) levels may vary with administration and discontinuation of pre-hepatectomy chemotherapy in patients undergoing resection of colorectal cancer liver metastases (CLM). The prognostic significance of these changes, termed CEA dynamics, is unclear.Patients and methodsConsecutive patients undergoing hepatectomy for CLM (2001-2021) at a comprehensive cancer center were included. CEA dynamics were classified as CEA normal (CEA < 5 ng/mL before, during, and after chemotherapy), CEA decrease (elevated CEA levels that drop during and after chemotherapy), and CEA rebound (elevated CEA levels that drop during chemotherapy but rebound upon discontinuation). Recurrence-free (RFS), hepatic-specific disease-free (hDFS), and overall survival (OS) were compared across CEA dynamics groups.ResultsOf 903 patients, 254 (28%) were CEA normal, 423 (47%) were CEA decrease, and 226 (25%) were CEA rebound. Median RFS was 15.9 months, median hDFS was not reached, and median OS was 11.9 years for CEA normal patients. By comparison, CEA decrease and CEA rebound patients had shorter median RFS (12.2 months, P = 0.002 and 7.4 months, P < 0.001, respectively), shorter median hDFS (29.1 months, P = 0.003 and 14.8 months, P < 0.001, respectively), and shorter median OS (7.1 years, P = 0.131, and 4.9 years, P < 0.001, respectively). On multivariable analysis, CEA rebound was an independent predictor of worse RFS [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.16-1.93], hDFS (HR 1.39, 95% CI 1.03-1.88), and OS (HR 1.79, 95% CI 1.18-2.73). Among patients with CEA rebound, RAS-BRAF/TP53 comutation and multiple tumors predicted worse OS while APC mutation predicted improved OS.ConclusionCEA rebound between pre-hepatectomy chemotherapy discontinuation and CLM resection is associated with worse oncologic outcomes, particularly in patients with aggressive tumor biology, and may help frame patient and surgeon expectations ahead of CLM resection.

Project description:BackgroundThe objective of this study was to compare the results of laparoscopic hepatectomy with those of open hepatectomy for colorectal cancer liver metastases (CCLM) using a propensity score matching (PSM) in two university hospital settings.MethodsA patient in the laparoscopic approach (LA) surgery group was randomly matched with another patient in the open approach (OA) group using a 1:1 allocated ratio with the nearest estimated propensity score. No patients of the LA group were excluded for the matching. Matching criteria included age, gender, body mass index (BMI), American society anesthesiologists score, potential co-morbidities, hepatopathies, synchronous or metachronous lesions, size and number of CCLM, preoperative chemotherapy, minor or major liver resections. Intraoperative, postoperative data, and survival were compared in both groups.ResultsFrom January 2012 to January 2015, a total of 242 hepatectomies were consecutively performed, of which 119 for CCLM, namely 101 in the OA group (84.9%) and 18 in the LA group (15.1%). The conversion rate was 5.6% (n=1). The mortality rate was 1% in the OA group and 0% in the LA group. Prior to PSM, there was a statistically significant difference favorable to the LA group regarding operative time, blood loss, length of hospital stay and the rate of medical complications. After PSM, there was no difference regarding operative time or length of hospital stay. However, there was a trend towards less blood loss (P=0.066) and fewer medical complications (44.4% vs.16.7%, P=0.07). The R0 resection rate was 94.4% (n=17) in the two groups. In addition, there was no difference regarding overall survival (P=0.358) and recurrence-free survival [HR =0.99 (0.1-12.7); P=0.99].ConclusionsLaparoscopic liver resections for CCLM seem to yield short- and long-term results, which are similar to open hepatectomies, and could well be considered an alternative to open surgery and become the gold standard in carefully selected patients.

Dataset Information

A transcriptomic signature that predicts cancer recurrence after hepatectomy in patients with colorectal liver metastases.

Background

Methods

Results

Conclusions

Publications

A transcriptomic signature that predicts cancer recurrence after hepatectomy in patients with colorectal liver metastases.

Similar Datasets

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