Prognostic Values of Immune Landscape in Ras-Mutant Colorectal Cancer Peritoneal Metastases
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PROVIDER: PRJNA813588 | ENA |
REPOSITORIES: ENA
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Project description:The peritoneal metastasis (PM) in patients with colorectal cancer (CRC) associated with poor survival, especially in those with Ras mutations. However, knowledge on the mechanism of molecular biology in CRC peritoneal metastasis (CRCPM) is limited, and the impact of tumor immune microenvironment (TME) on PM pathogenesis and the prognosis of CRCPM remains unclear. Therefore, we characterized the TME of CRCPM and evaluated its potential diagnostic and prognostic values. This study involved 21 patients with metastatic CRC (mCRC), of whom 11 with CRCPM were classified into the experimental group and 10 with mCRC without PM (noCRCPM) were classified into the control group. Formalin-fixed and paraffin-embedded tissue of primary tumors from all patients was examined using the NanoString RNA sequencing system. The clinicopathological variables and TME biomarkers were compared using the chi-square test and Cox regression analysis. According to the results of multivariate analysis, a prognostic nomogram was generated, and its prediction ability was measured using the concordance index (C-index). Survival curves were generated using the Kaplan–Meier method, and survival comparison between groups was conducted using the log-rank test.
2022-10-01 | GSE198085 | GEO
Project description:Purpose: At diagnosis, colorectal cancer presents with synchronous peritoneal metastasis in up to 10% of patients. The peritoneum is poorly characterized with respect to its super-specialised microenvironment. Our aim was to describe the differences between peritoneal metastases and their matched primary tumours excised simultaneously at the time of surgery. Also, we tested the hypothesis of these differences being present in primary colorectal tumours and having prognostic capacity. Experimental design: We report a comprehensive analysis of thirty samples from peritoneal metastasis with their matched colorectal cancer primaries obtained during cytoreductive surgery. We tested and validated the prognostic value of our findings in a pooled series of 660 colorectal cancer primary samples with overall survival (OS) information and 743 samples with disease free survival (DFS) information from publicly available databases. Results: We identified 20 genes dysregulated in peritoneal metastasis that promote an early increasing role of ‘stemness’ in conjunction with tumour favorable inflammatory changes. When adjusted for age, gender and stage, the 20-gene peritoneal signature proved to have prognostic value for both OS (adjusted-hazard ratio (HR) for the high-risk group (vs low-risk) 2.32 (95% confidence interval (CI) 1.69-3.19; p-value < 0.0001)) and for DFS (adjusted-HR 2.08 (95%CI 1.50-2.91; p-value < 0.0001)). Conclusions: Our findings indicated that the activation of “stemness” pathways and adaptation to the peritoneal specific environment are key to early stages of peritoneal carcinomatosis. The in-silico analysis suggested that this 20-gene peritoneal signature may hold prognostic information with potential for development of new precision medicine strategies in this setting.
2020-11-13 | GSE161097 | GEO
Project description:Patients with peritoneal metastases (PM) originating from colorectal carcinoma (CRC) are curatively treated by cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) with Mitomycin C (MMC). We aim to improve patient selection and personalize treatment for patients treated with HIPEC by predicting MMC sensitivity. MMC sensitivity was determined for 12 CRC cell lines using two separate assays. Thirty-seven genes related to the FA-BRCA pathway, ATM-ATR pathway and enzymatic activation of MMC were correlated on expression array platform to MMC sensitivity. Low sensitivity correlated with a decrease in BLM (p=0.01) and BRCA2 (p=0.02) on mRNA expression level. Both genes are part of the Fanconi Anaemia-BRCA (FA-BRCA) pathway and therefore, functionality of the FA-BRCA pathway in cell lines was determined using chromosomal breakage assay and Western Blot for key protein FANCD2. However, FA-BRCA pathway functionality showed no correlation to MMC sensitivity. BLM was further analysed by staining for the corresponding protein with immunohistochemistry (IHC) on both CRC cell lines and patient material. In cell lines, weak intensity staining by IHC correlated to high sensitivity (p=0.04) to MMC. High BLM protein expression was significantly correlated to a decreased survival in patients after CRS and HIPEC (p=0.04). We are the first to have found a possible predictive biomarker for PM with CRC.
2015-12-01 | GSE50494 | GEO
Project description:Exploiting a subtype-specific mitochondrial vulnerability for successful treatment of colorectal peritoneal metastases
| PRJNA1014010 | ENA
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: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:Gene expression profiles were generated from 41 consecutive surgically resected fresh frozen malignant peritoneal mesothelioma patient tumor samples to identify molecular prognostic factors.
2010-09-27 | GSE15627 | GEO
Project description:Background: There is a paucity of targeted therapies for patients with pseudomyxoma peritonei (PMP) secondary to low-grade appendiceal mucinous neoplasms (LAMNs). Dysregulated metabolism has emerged as a hallmark of cancer, and the relationship of metabolomics and cancer is an area of active scientific exploration. We sought to characterize phenotypic differences found in peritoneal metastases (PM) derived from LAMN versus adenocarcinoma. Methods: Tumors were washed with phosphate-buffered saline (PBS), microdissected, then dissociated in ice-cold methanol dried and reconstituted in pyridine. Samples were derivatized in tert-butyldimethylsilyl (TBDMS) and subjected to gas chromatography-coupled mass spectrometry. Metabolites were assessed based on a standard library. RNA sequencing was performed, with pathway and network analyses on differentially expressed genes.Results: Eight peritoneal tumor samples were obtained and analyzed: LAMNs (4), and moderate to poorly differentiated adenocarcinoma (colon [1], appendix [3]). Decreases in pyroglutamate, fumarate, and cysteine in PM from LAMNs were found compared with adenocarcinoma. Analyses showed the differential gene expression was dominated by the prevalence of metabolic pathways, particularly lipid metabolism. The gene retinol saturase (RETSAT), downregulated by LAMN, was involved in the multiple metabolic pathways that involve lipids. Using network mapping, we found IL1B signaling to be a potential top-level modulation candidate. Conclusions: Distinct metabolic signatures may exist for PM from LAMN versus adenocarcinoma. A multitude of genes are differentially regulated, many of which are involved in metabolic pathways. Additional research is needed to identify the significance and applicability of targeting metabolic pathways in the potential development of novel therapeutics for these challenging tumors.
2024-05-01 | GSE266352 | GEO
Project description:A Novel Assessment of Metabolic Pathways in Peritoneal Metastases from Low-Grade Appendiceal Mucinous Neoplasms
| PRJNA1106805 | ENA
Project description:Gene expression profiles were generated from 41 consecutive surgically resected fresh frozen malignant peritoneal mesothelioma patient tumor samples to identify molecular prognostic factors. Patient tumor samples hybridized against the common reference (complementary DNA generated from human universal RNA), 41 tumor samples.
2010-09-27 | E-GEOD-15627 | biostudies-arrayexpress