Gene expression profiling of liver metastases from colorectal cancer as potential basis for treatment choice.
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ABSTRACT:
SUBMITTER: Pantaleo MA
PROVIDER: S-EPMC2584956 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Liver resection is the only potentially curative treatment option in patients with liver metastases from colorectal cancer, but only about 20% of the patients are resectable. Liver transplantation of patients with unresectable liver metastases was attempted in the early era but it was abandoned due to poor survival. During the last decade, several case reports, a controlled pilot study, and a retrospective cohort study indicated that prolonged disease-free survival and overall survival can be obtained in a proportion of these patients. Strict selection criteria have not yet been well defined, but tumor load, response to chemotherapy, pretransplant carcinoembryonic antigen level, and time interval from resection of the primary tumor to transplant are all factors related to outcome. Carefully selected patients may obtain 5-year overall survival that approaches conventional indications for liver transplant. The scarcity of liver grafts is a significant problem, but this can possibly to some extent be addressed by use of extended criteria grafts and novel surgical techniques. There is an increasing interest in liver transplantation in these patients in the transplant community, and currently 4 clinical trials are active and are recruiting.
| S-EPMC5829437 | biostudies-literature
Project description:Colorectal cancer (CRC) is the third most common cancer in the word. Liver metastasis is the most common site of colorectal metastases. The prognosis of resectable colorectal liver metastases (CRLM) was improved in the recent years with the consideration of chemotherapy and surgical resection as part of the multidisciplinary management of the disease; the current 5-year survival rates after resection of liver metastases are 25% to 40%. Resectable synchronous or metachronous liver metastases should be treated with perioperative chemotherapy based on three months of FOLFOX4 (5-fluorouracil [5FU], folinic acid [LV], and oxaliplatin) chemotherapy before surgery and three months after surgery. In the case of primary surgery, pseudo-adjuvant chemotherapy for 6 months, based on 5FU/LV, FOLFOX4, XELOX (capecitabine and oxaliplatin) or FOLFIRI (5FU/LV and irinotecan), should be indicated. In potentially resectable disease, primary chemotherapy based on more intensive regimens such as FOLFIRINOX (5FU/LV, irinotecan and oxaliplatin) should be considered to enhance the chance of cure. The palliative chemotherapy based on FOLFIRI, or FOLFOX4/XELOX with or without targeted therapies, is the mainstay treatment of unresectable disease. This review would provide additional insight into the problem of optimal integration of chemotherapy and surgery in the management of CRLM.
| S-EPMC3251538 | biostudies-other
Project description:BACKGROUND: Despite the fact that metastases are the leading cause of colorectal cancer deaths, little is known about the underlying molecular changes in these advanced disease stages. Few have studied the overall gene expression levels in metastases from colorectal carcinomas, and so far, none has investigated the peritoneal carcinomatoses by use of DNA microarrays. Therefore, the aim of the present study is to investigate and compare the gene expression patterns of primary carcinomas (n = 18), liver metastases (n = 4), and carcinomatoses (n = 4), relative to normal samples from the large bowel. RESULTS: Transcriptome profiles of colorectal cancer metastases independent of tumor site, as well as separate profiles associated with primary carcinomas, liver metastases, or peritoneal carcinomatoses, were assessed by use of Bayesian statistics. Gains of chromosome arm 5p are common in peritoneal carcinomatoses and several candidate genes (including PTGER4, SKP2, and ZNF622) mapping to this region were overexpressed in the tumors. Expression signatures stratified on TP53 mutation status were identified across all tumors regardless of stage. Furthermore, the gene expression levels for the in vivo tumors were compared with an in vitro model consisting of cell lines representing all three tumor stages established from one patient. CONCLUSION: By statistical analysis of gene expression data from primary colorectal carcinomas, liver metastases, and carcinomatoses, we are able to identify genetic patterns associated with the different stages of tumorigenesis.
| S-EPMC1770935 | biostudies-literature
Project description:Gene expression profiling of colorectal cancer liver metastases (CRLM).
| PRJNA668063 | ENA
Project description:Surgical resection is the only curative modality for colorectal liver metastases (CLM) and 5-year overall survival after resection is about 40%. Nonresectable CLM is not curable and 5-year overall survival is currently about 10%. Before 1995, several liver transplantations for CLMs were performed, but outcome was poor (5-year survival rate: 18%). Liver transplantation for CLMs was abandoned and CLMs were even considered a contraindication to the procedure. Since then, the survival rate after liver transplantation in general has improved by almost 30%. In a prospective pilot study of liver transplantation for nonresectable CLM, a 5-year overall survival rate of 60% was demonstrated, however 19 of 21 patients experienced recurrence of disease. Here, current knowledge and ongoing research in this field is reviewed, and the potential role for liver transplantation as one of several treatment modalities for CLM discussed.
| S-EPMC6095405 | biostudies-other
Project description:We have performed gene expression profiling of surgically resected liver metastases by exon-resolution microarrays, and identified a metastasis-oriented subtyping framework consisting of 5 de novo transcriptomic subtypes (LMS1-5).
2021-07-27 | GSE159216 | GEO
Project description:At present, medical treatments of synchronous and metachronous liver metastases from colorectal cancer are not differentiated. The aim of the study was to analyze the gene expression profiling of synchronous and metachronous lesions in order to identify molecular signatures as possible basis for choice of systemic therapies. Fresh tissues specimens from metastases of 18 patients undergone liver surgery were collected (10 synchronous and 8 metachronous lesions). Gene expression profiling was studied using Affymetrix platform. Two different profiles were identified. Pathway related to the Epidermal Growth Factor receptor (EGFr) was upregulated in metachronous lesions whereas pathways mainly related to inflammation in synchronous lesions. Real Time-PCR, Western Blotting and ELISA confirmed that the metachronous lesions had the overexpression of EGFr, but the synchronous ones had the overexpression of Cyclo-oxygenase 2 (COX-2). These results suggest that synchronous or metachronous liver metastases from colorectal cancer could be differently treated on the basis of different molecular pathways. Keywords: disease state analysis
2008-12-22 | GSE10961 | GEO
Project description:The circadian timing system controls about 40 % of the transcriptome and is important in the regulation of a wide variety of biological processes including metabolic and proliferative functions. Disruption of the circadian clock could have significant effect on human health and has an important role in the development of cancer. Here, we compared the expression levels of core clock genes in primary colorectal cancer (CRC), colorectal liver metastases (CRLM), and liver tissue within the same patient. Surgical specimens of 15 untreated patients with primary CRC and metachronous CRLM were studied. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of 10 clock genes: CLOCK, BMAL1, PER1, PER2, PER3, CRY1, CRY2, CSNK1E, TIM, TIPIN, and 2 clock-controlled genes: Cyclin-D1, and WEE1. Expression levels of 7 core clock genes were downregulated in CRLM: CLOCK (p?=?0.006), BMAL1 (p?=?0.003), PER1 (p?=?0.003), PER2 (p?=?0.002), PER3 (p?<?0.001), CRY1 (p?=?0.002), and CRY2 (p?<?0.001). In CRC, 5 genes were downregulated: BMAL1 (p?=?0.02), PER1 (p?=?0.004), PER2 (p?=?0.008), PER3 (p?<?0.001), and CRY2 (p?<?0.001). CSNK1E was upregulated in CRC (p?=?0.02). Cyclin-D1 and WEE1 were both downregulated in CRLM and CRC. Related to clinicopathological factors, a significant correlation was found between low expression of CRY1 and female gender, and low PER3 expression and the number of CRLM. Our data demonstrate that the core clock is disrupted in CRLM and CRC tissue from the same patient. This disruption may be linked to altered cell-cycle dynamics and carcinogenesis.
| S-EPMC5097083 | biostudies-other
Project description:Patients presenting with synchronous or metachronous colorectal cancer liver metastases (CLM) should be evaluated for multimodal management with curative intent. Preoperative systemic chemotherapy shows beneficial impact on adjuvant progression-free survival and also borderline on overall survival, without significantly increasing initially R0 resectable patients postoperative complication rates. Postoperative chemotherapy recommended based on the perioperative trial experience for those patients achieving at least stable disease during preoperative chemotherapy, or based on the adjuvant trials for patients receiving upfront resection. 'Borderline' resectable CLM, preoperative chemotherapy plays an important role in both in achievement of a resectable status and improvement of prognosis. Recent 4 drug combinations demonstrated response rates up to 80% even for advanced disease and are thus promising regimens for further evaluation in patients with resectable or unresectable liver-limited (+/- lung) disease.
| S-EPMC3630480 | biostudies-literature
Project description:mRNA sequencing by Lexogen Quantseq 3 prime of colorectal liver metastases
| PRJEB35154 | ENA