LGR5 expression predicts peritoneal recurrence after curative resection of primary colon cancer.
Ontology highlight
ABSTRACT: Background
The aim of this study was to clarify whether a cancer stem cell marker could be an indicator of post-operative peritoneal recurrence of colon cancer.Methods
Expression of four putative markers (CD133, CD44 variant 6, aldehyde dehydrogenase-1 and leucine-rich repeating G-protein-coupled receptor-5 (LGR5)) was evaluated immunohistochemically in primary tumour samples from 292 patients who underwent curative resection for non-metastasised pT4 colon cancer at the University of Tokyo Hospital between 1997 and 2015.Results
Peritoneal recurrence was significantly higher in LGR5-negative cases (5-year cumulative incidence: 27.5% vs. 14.4%, p = 0.037). Multivariable analysis confirmed that negative LGR5 expression was an independent risk factor for peritoneal recurrence (hazard ratio (HR) 2.79, p = 0.005) in addition to poor differentiation, positive lymph node metastasis, preoperative carcinoembryonic antigen > 5 ng/mL and anastomotic leakage. The addition of LGR5 significantly improved the predictive value of the multivariable model (net reclassification improvement: 0.186, p = 0.028: integrated discrimination improvement: 0.047, p = 0.008).Conclusions
Negative LGR5 expression was a significant predictor of peritoneal recurrence in patients with pT4 colon cancer. Therefore, LGR5 might be a promising biomarker to identify patients at high risk of post-operative peritoneal metastasis.
SUBMITTER: Nagata H
PROVIDER: S-EPMC6734652 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:(1) Background: The aim of this study was to develop a prediction model for assessing individual mPC risk in patients with pT4 colon cancer. Methods: A total of 2003 patients with pT4 colon cancer undergoing R0 resection were categorized into the training or testing set. Based on the training set, 2044 Cox prediction models were developed. Next, models with the maximal C-index and minimal prediction error were selected. The final model was then validated based on the testing set using a time-dependent area under the curve and Brier score, and a scoring system was developed. Patients were stratified into the high- or low-risk group by their risk score, with the cut-off points determined by a classification and regression tree (CART). (2) Results: The five candidate predictors were tumor location, preoperative carcinoembryonic antigen value, histologic type, T stage and nodal stage. Based on the CART, patients were categorized into the low-risk or high-risk groups. The model has high predictive accuracy (prediction error ≤5%) and good discrimination ability (area under the curve >0.7). (3) Conclusions: The prediction model quantifies individual risk and is feasible for selecting patients with pT4 colon cancer who are at high risk of developing mPC.
| S-EPMC8200190 | biostudies-literature
Project description:Purpose: Our study aimed to disclose the specific gene expression profile representing peritoneal relapses inherent in primary gastric cancers and to identify patients at high risk of peritoneal relapse in a prospective study on the basis of the molecular prediction. Experimental Design: RNA samples from 141 primary gastric cancer tissues after curative surgery were profiled using oligonucleotide microarrays covering 30,000 human probes. Firstly we constructed molecular prediction system and validated the robustness and prognostic validity of the analysis by 500 times multiple random sampling in 56 retrospective set consisting of 38 relapse free and 18 peritoneal relapse patients. Secondly we applied this prediction to 85 prospective set to assess the predictive accuracy and prognostic validity. Results: In retrospective phase, 500 times multiple random sampling analysis yielded 68% predictive accuracy in average and 22 gene expression profile associated with peritoneal relapse was identified. This prediction could identify significantly poor prognostic patients. In prospective phase, the molecular prediction yielded 76.9% overall accuracy. Kaplan–Meier analysis with peritoneal relapse free survival showed a significant difference between ‘good signature group’ and ‘poor signature group’ (Log-rank p=0.0017). Multivariate analysis by Cox regression hazards model revealed that the molecular prediction was the only independent peritoneal relapse prognostic factor. Conclusions: Gene expression profile inherent in primary gastric cancer tissues can be useful to predict peritoneal relapse prospectively after curative surgery and individualize postoperative management to improve the prognosis of advanced gastric cancers.
2009-03-04 | GSE15081 | GEO
Project description:BackgroundImmunoscore have shown a promising prognostic value in many cancers. We aimed to establish and validate an immune classifier to predict survival after curative resection of hepatocellular carcinoma (HCC) patients who have undergone curative resection.MethodsThe immunohistochemistry (IHC) classifier assay was performed on 664 patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A HCC. A nine-feature-based HCC-IHC classifier was then constructed by the least absolute shrinkage and selection operator method. The associations between the HCC-IHC classifier and patient outcomes were assessed. Herein, a nomogram was generated from the Cox regression coefficients and evaluated by decision curve analysis.ResultsWe constructed an HCC-IHC classifier based on nine features; significant differences were found between the low-HCC-IHC classifier patients and high-HCC-IHC classifier patients in the training cohort in the 5-year relapse-free survival rates (46.7% vs. 26.7%, respectively; P < 0.001). The HCC-IHC classifier-based nomogram presented better accuracy than traditional staging systems.ConclusionsIn conclusion, the HCC-IHC classifier could effectively predict recurrence in early-stage HCC patients and supplemented the prognostic value of the BCLC staging system. The HCC-IHC classifier may facilitate patient decision-making and individualise the management of postoperative patients with early-stage HCC.
| S-EPMC7341807 | biostudies-literature
Project description:BackgroundOur recent study observed that the expression of ubiquitin D (UBD), a member of ubiquitin-like modifier family, was upregulated in colon cancer parenchymal cells. The present study further investigated the clinical signicance of UBD in colon cancer.MethodsUsing quantitative PCR, tissue microarray (TMA), western blot analysis and immunohistochemical stain, we evaluated UBD mRNA and protein levels in tumour tissues from patients with colon cancer at different stages and in paired adjacent normal epithelium.ResultsImmunohistochemical detection of UBD on a TMA containing 203 paired specimens showed that increased cytoplasmic UBD was signicantly associated with depth of cancer invasion, lymph node metastasis, distant metastasis, tumour histologic grade, advanced clinical stage and Ki-67 proliferative index. Patients with UBD-positive tumours had a significantly higher disease recurrence rate and poorer survival than patients with UBD-negative tumours after the radical surgery. Stratification analysis according to tumour stage revealed UBD as an independent predictor for tumour recurrence in patients with stage II and III tumours.ConclusionUBD may contribute to the progression of colon carcinogenesis and function as a novel prognostic indicator of forecasting recurrence of stage II and III patients after curative operations.
| S-EPMC2965875 | biostudies-literature
Project description:Purpose: Our study aimed to disclose the specific gene expression profile representing peritoneal relapses inherent in primary gastric cancers and to identify patients at high risk of peritoneal relapse in a prospective study on the basis of the molecular prediction. Experimental Design: RNA samples from 141 primary gastric cancer tissues after curative surgery were profiled using oligonucleotide microarrays covering 30,000 human probes. Firstly we constructed molecular prediction system and validated the robustness and prognostic validity of the analysis by 500 times multiple random sampling in 56 retrospective set consisting of 38 relapse free and 18 peritoneal relapse patients. Secondly we applied this prediction to 85 prospective set to assess the predictive accuracy and prognostic validity. Results: In retrospective phase, 500 times multiple random sampling analysis yielded 68% predictive accuracy in average and 22 gene expression profile associated with peritoneal relapse was identified. This prediction could identify significantly poor prognostic patients. In prospective phase, the molecular prediction yielded 76.9% overall accuracy. KaplanâMeier analysis with peritoneal relapse free survival showed a significant difference between âgood signature groupâ and âpoor signature groupâ (Log-rank p=0.0017). Multivariate analysis by Cox regression hazards model revealed that the molecular prediction was the only independent peritoneal relapse prognostic factor. Conclusions: Gene expression profile inherent in primary gastric cancer tissues can be useful to predict peritoneal relapse prospectively after curative surgery and individualize postoperative management to improve the prognosis of advanced gastric cancers. Of 141 samples, 56 represented the retrospective phase and 85 represented the prospective phase.
2010-05-23 | E-GEOD-15081 | biostudies-arrayexpress
Project description:Intrahepatic cholangiocarcinoma (ICC) is a cancer type with high malignancy and a current lack of biomarkers to predict recurrence. In the present study, to identify potential biomarkers, five ICC datasets from the Gene Expression Omnibus database were analyzed to construct initial datasets by using a robust rank aggregation approach. A total of 19 upregulated genes were identified in the initial datasets. The genes identified were then further analysed using data from The Cancer Genome Atlas. Only mucin 1 (MUC1) exhibited significance regarding differential expression and survival prediction. Finally, the expression levels of MUC1 were assessed using reverse transcription-quantitative PCR in 61 pairs of ICC tumor and matched non-cancerous samples. The expression of MUC1 was significantly elevated in ICC tissues compared with that in matched non-cancerous counterparts (P=0.001). Patients with high MUC1 expression levels had significantly shorter overall survival (OS, P=0.009) and recurrence-free survival (RFS, P=0.012). MUC1 was identified as an independent prognostic factor for OS [hazard ratio (HR)=2.364, 95%CI: 1.214-4.485; P=0.023] and RFS (HR=2.552 95%CI: 1.294-5.032; P=0.007) in the multivariate analysis. Using receiver operating characteristic analysis, a co-index including MUC1 had a high accuracy for predicting survival [MUC1 combined with serum levels of CEA and cancer antigen 19-9, and lymph node metastasis, area under curve (AUC)=0.746, 95%CI: 0.620-0.872] and recurrence (MUC1 combined with bile duct invasion and lymph node metastasis, AUC=0.729, 95%CI: 0.605-854). In conclusion, MUC1 is highly expressed in ICC tissue and is a potential prognostic biomarker and therapeutic target for ICC.
| S-EPMC7480127 | biostudies-literature
Project description:PurposePatients with rectal cancer without distant metastases are typically treated with radical surgery. Post curative resection, several factors can affect tumor recurrence. This study aimed to analyze factors related to rectal cancer recurrence after curative resection using different machine learning techniques.MethodsConsecutive patients who underwent curative surgery for rectal cancer between 2004 and 2018 at Gil Medical Center were included. Patients with stage IV disease, colon cancer, anal cancer, other recurrent cancer, emergency surgery, or hereditary malignancies were excluded from the study. The Synthetic Minority Oversampling Technique with Tomek link (SMOTETomek) technique was used to compensate for data imbalance between recurrent and no-recurrent groups. Four machine learning methods, logistic regression (LR), support vector machine (SVM), random forest (RF), and Extreme gradient boosting (XGBoost), were used to identify significant factors. To overfit and improve the model performance, feature importance was calculated using the permutation importance technique.ResultsA total of 3320 patients were included in the study. After exclusion, the total sample size of the study was 961 patients. The median follow-up period was 60.8 months (range:1.2-192.4). The recurrence rate during follow-up was 13.2% (n = 127). After applying the SMOTETomek method, the number of patients in both groups, recurrent and non-recurrent group were equalized to 667 patients. After analyzing for 16 variables, the top eight ranked variables {pathologic Tumor stage (pT), sex, concurrent chemoradiotherapy, pathologic Node stage (pN), age, postoperative chemotherapy, pathologic Tumor-Node-Metastasis stage (pTNM), and perineural invasion} were selected based on the order of permutational importance. The highest area under the curve (AUC) was for the SVM method (0.831). The sensitivity, specificity, and accuracy were found to be 0.692, 0.814, and 0.798, respectively. The lowest AUC was obtained for the XGBoost method (0.804), with a sensitivity, specificity, and accuracy of 0.308, 0.928, and 0.845, respectively. The variable with highest importance was pT as assessed through SVM, RF, and XGBoost (0.06, 0.12, and 0.13, respectively), whereas pTNM had the highest importance when assessed by LR (0.05).ConclusionsIn the current study, SVM showed the best AUC, and the most influential factor across all machine learning methods except LR was found to be pT. The rectal cancer patients who have a high pT stage during postoperative follow-up are need to be more close surveillance.
| S-EPMC10723658 | biostudies-literature
Project description:To improve the outcome of gastric cancer, novel markers that predict postoperative prognosis are required. For this purpose, the function of cellular retinoic acid binding protein 1 (CRABP1) in gastric cancer cells was investigated and it was determined whether it serves as a novel biomarker for gastric cancer. Reverse transcription‑quantitative (RT‑q)PCR and a PCR‑array method were used to determine whether the expression of CRABP1 mRNA in gastric cancer cell lines correlated with the expression of cancer‑related genes. The correlations of CRABP1 mRNA expression in tissues with clinicopathological factors of 230 patients who underwent radical gastrectomy were further evaluated. CRABP1 mRNA levels varied among gastric cancer cell lines and showed significant positive correlations with numerous epithelial‑mesenchymal transition factors. Additionally, CRABP1 knockdown significantly suppressed the proliferation, migration and invasion of gastric cancer cell lines. In a mouse xenograft model of peritoneal metastasis of gastric cancer, it was found that the total weight of disseminated nodules was lower in the group, in which CRABP1 mRNA levels were knocked down compared with those of the untransfected group. Disease‑free survival (DFS) was significantly shorter in patients with high expression of CRABP1, and multivariate analysis of DFS revealed that high expression of CRABP1 in the tumor area and lymph node metastasis served as an independent factor associated with poor prognosis. High expression of CRABP1 in cancer tissues was associated with a greater incidence of peritoneal recurrences after curative gastrectomy. These findings indicated that CRABP1 contributes to the malignant phenotype of gastric cancer cells and may serve as a biomarker for prognosing recurrence after curative resection, particularly peritoneal dissemination.
| S-EPMC9015192 | biostudies-literature
Project description:BackgroundThe aim of this study was to determine the prognostic value of embryonic origin in patients undergoing resection after chemotherapy for colon cancer liver metastases (CCLM).MethodsWe identified 725 patients with primary colon cancer and known RAS mutation status who underwent hepatic resection after preoperative chemotherapy for CCLM (1990 to 2015). Survival after resection of CCLM from midgut origin (n = 238) and hindgut origin (n = 487) was analyzed. Predictors of pathologic response and survival were determined. Prognostic value of embryonic origin was validated with a separate cohort of 252 patients with primary colon cancer who underwent resection of CCLM without preoperative chemotherapy.ResultsRecurrence-free survival (RFS) and overall survival (OS) after hepatic resection were worse in patients with midgut origin tumors (RFS rate at 3 years: 15% vs 27%, P < 0.001; OS rate at 3 years: 46% vs 68%, P < 0.001). Independent factors associated with minor pathologic response were midgut embryonic origin [odds ratio (OR) 1.55, P = 0.010], absence of bevacizumab (OR 1.42, P = 0.034), and mutant RAS (OR 1.41, P = 0.043). Independent factors associated with worse OS were midgut embryonic origin [hazard ratio (HR) 2.04, P < 0.001], carcinoembryonic antigen value ≥5 ng/mL at hepatic resection (HR 1.46, P = 0.0021), synchronous CCLM (HR 1.45, P = 0.012), and mutant RAS (HR 1.43, P = 0.0040). In the validation cohort, patients with CCLM of midgut origin had a worse 3-year OS rate (55% vs 78%, P = 0.003).ConclusionsCompared with CCLM from hindgut origin, CCLM from midgut origin are associated with worse pathologic response to chemotherapy and worse survival after resection. This effect appears to be independent of RAS mutation status.
| S-EPMC5901745 | biostudies-literature
Project description:Outcomes of patients with gastric cancer who exhibit positive peritoneal lavage cytology findings (CY+ ) vary by diagnostic methods because of quantitative and qualitative cancer cell diversity. This study sought to establish practical diagnostic criteria for performing curative resections, based on peritoneal lavage cytology findings in gastric cancer patients. We enrolled 1028 patients with gastric cancer who underwent R0/1 (n = 911) or R2 (n = 117) resections and analyzed relationships between cancer cell findings in peritoneal lavage fluid and clinicopathological factors in the R0/1 group. We found 68 patients with CY+ status. Receiver operating characteristic analyses and multivariate analyses showed that the presence of ?1 signet ring cell, ?5 cell clusters or ?50 isolated cancer cells in peritoneal lavage fluid predicted poor prognoses in the 68 CY+ patients. High-risk CY+ group patients with at least one of the above predictors had the highest hazard ratio (HR = 3.28, P < 0.001). The remaining (low-risk) patients had a survival curve similar to that of patients with a normal cytology. The high-risk CY+ patients who underwent R1 resection had poor prognoses despite no macroscopic peritoneal metastasis (2% 5-year survival)-equivalent to that of patients who underwent R2 resection. The CY+ criteria defined in this study could help identify candidates for curative resection as an initial therapy for gastric cancer.
| S-EPMC5448654 | biostudies-literature