Regional chemotherapy for patients with liver only recurrence after previous resection of liver metastasis of colorectal cancer.
Ontology highlight
ABSTRACT:
DISEASE(S): Liver Recurrence After Hepatectomy For Crlm.
PROVIDER: 2539639 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Identification of specific risk groups for recurrence after surgery for colorectal liver metastases (CRLM) remains challenging due to the heterogeneity of the disease. Classical clinicopathologic parameters have limited prognostic and predictive value. The aim of this study was to identify a gene expression signature measured in CRLM discriminating early from late recurrence after surgery for CRLM. Methods: Tumour samples of CRLM from two patient groups were collected: I) patients with recurrent disease within 12 months after surgery (N=33), and II) patients without recurrences and disease free for at least 36 months (N=30). The included patients were clinically homogeneous; all patients had a low risk profile (clinical risk score 0-2) and did not receive (neo-) adjuvant chemotherapy. Extracted total RNA from both groups was hybridized to Illumina arrays, and processed for analysis. A leave-one-out cross validation (LOOCV) analysis was performed to identify a potentially prognostic gene expression signature. Results: The LOOCV yielded an 11-gene profile with prognostic value in relation to recurrent disease within 12 months after partial hepatectomy. This gene expression profile had a sensitivity of 81.8%, with a specificity of 66.7% for predicting early recurrences (within 12 months) versus no recurrences for at least 36 months after surgery (X2 P<0.0001). Conclusion: The current study yielded an 11-gene signature at mRNA level in CRLM discriminating early from late or no relapse after partial hepatectomy.
2017-01-01 | GSE81423 | GEO
Project description:Colorectal cancer (CRC) patients suffer from the second highest mortality among all cancer entities. In half of all CRC patients, colorectal cancer liver metastases (CRLM) can be observed. Metastatic colorectal cancer is associated with poor overall survival and limited treatment options. Even after successful surgical resection of the primary tumor, metachronous liver metastases occur in one out of eight cases. The only available curative intended treatment is hepatic resection, but metachronous CRLM frequently recur after approximately one year. In this study, we performed a proteome analysis of three recurrent liver metastases of a single CRC patient by mass spectrometry. Despite surgical resection of the primary CRC and adjuvant chemotherapy plus cetuximab treatment, the patient developed three metachronous CRLM which occurred consecutively after 9, 21 and 31 months. We identified a set of 1,132 proteins expressed in the three metachronous CRLM, of which 481 were differentially regulated, including 81 proteins that were associated with the extracellular matrix (ECM). 56 ECM associated proteins were identified as upregulated in the third metastasis, 26 (46%) of which were previously described as negative prognostic markers in CRC, including tenascin C, nidogen 1, fibulin1 and vinculin. These data may reflect an ascending trend of malignancy from the first to the third metachronous colorectal cancer liver metastasis. Additionally, the results indicate different ECM phenotypes for recurrent metachronous metastasis, associated with different grades of malignancy and highlights the importance of individual analysis of molecular features in different, consecutive metastatic events in a single patient.
2021-09-09 | PXD020109 | Pride
Project description:The primary objective is to demonstrate superiority of neoadjuvant systemic therapy followed by repeat local treatment as compared to upfront repeat local treatment in patients with at least one locally treatable recurrent CRLM in the absence of extrahepatic disease.
| 60270 | ecrin-mdr-crc
Project description:For patients with initially unresectable colorectal liver metastasis (IU-CRLM) receiving effective conversion therapy, disease relapse after conversion hepatectomy is common due to the extensive tumor load. Yet, few studies have focused on the assessment and management of relapse after conversion hepatectomy for IU-CRLM. This study aimed to investigate the impact of surgical management for relapse after conversion hepatectomy in IU-CRLM.
| 2742045 | ecrin-mdr-crc
Project description:We determined whether collagen is upregulated in colorectal liver metastasis tissue (CRLM). We previously showed that naturally occurring peptides of collagen type I were elevated in the urine of patients with colorectal liver metastasis (CRLM). CRLM tissue was compared to healthy adjacent liver tissue (controls) using high resolution mass spectrometry. Twenty-two different collagen alpha chains were identified, 19 of which were significantly upregulated (P<0.05) in CRLM tissue compared with control tissue. We observed expression of four collagen alpha chains which were absent or low expressed in healthy colon and control tissue, but were highly present in CRC and CRLM tissues analyzed. This expression pattern was also observed for six non-collagen colon specific proteins. Two of these proteins (CDH17 and PPP1R1B/DARP-32) were not known to be differently expressed in CRLM in comparison to healthy liver tissue. Furthermore, 16 of 20 identified proteins related to collagen synthesis were upregulated, indicating increased synthesis of collagen in CRLM. Cross-validation of the mass spectrometry data with immunohistochemistry for collagen type XII confirmed the significant upregulation of collagen type XII in CRLM. This study shows that the majority of collagen types are upregulated in CRLM compared to control tissue most likely as a result of an increased collagen turnover and changes in the collagen supramolecular structure. This research provides further understanding of morphologic changes in extracellular matrix of CRLM and the finding of proteins and peptides that might be specific for tumor metastasis in liquid biopsies.
2018-11-21 | PXD008383 | Pride
Project description:The tumor microenvironment is distinctive in primary and secondary liver cancer. B cells represent an important component of immune infiltrates. Here, we demonstrated that B cells are an important regulator in hepatocellular carcinoma (HCC) and colorectal cancer liver metastasis (CRLM) microenvironments. B cells displayed distinct developmental trajectories in HCC and CRLM. Single-cell analysis revealed that IgG+ plasma cells preferentially accumulated in HCC while IgA+ plasma cells were preferentially enriched in CRLM. Mechanistically, IgG+ plasma cells in HCC were recruited by tumor-associated macrophages via the CXCR3-CXCL10 axis, whereas IgA+ plasma cells in CRLM were recruited by metastatic tumor cells via CCR10-CCL28 signaling. Functionally, IgG+ plasma cells preferentially promoted pro-tumorigenic macrophages formation in HCC, and IgA+ plasma cells preferentially induced granulocytic myeloid-derived suppressor cells activation in CRLM. Clinically, increased infiltration of IgG+ plasma cells and macrophages in HCC was correlated to worse survival, while increased intratumoral IgA+ plasma cells and neutrophils in CRLM indicated poor prognosis. Taken together, this study demonstrated plasma and myeloid cell-mediated immunosuppression in HCC and CRLM, suggesting that selectively modulating primary or secondary tumor-related immunosuppressive regulatory networks might reprogram the microenvironment and provide an immunotherapeutic strategy for treating liver cancer.
2023-09-17 | GSE243245 | GEO
Project description:The tumor microenvironment is distinctive in primary and secondary liver cancer. B cells represent an important component of immune infiltrates. Here, we demonstrated that B cells are an important regulator in hepatocellular carcinoma (HCC) and colorectal cancer liver metastasis (CRLM) microenvironments. B cells displayed distinct developmental trajectories in HCC and CRLM. Single-cell analysis revealed that IgG+ plasma cells preferentially accumulated in HCC while IgA+ plasma cells were preferentially enriched in CRLM. Mechanistically, IgG+ plasma cells in HCC were recruited by tumor-associated macrophages via the CXCR3-CXCL10 axis, whereas IgA+ plasma cells in CRLM were recruited by metastatic tumor cells via CCR10-CCL28 signaling. Functionally, IgG+ plasma cells preferentially promoted pro-tumorigenic macrophages formation in HCC, and IgA+ plasma cells preferentially induced granulocytic myeloid-derived suppressor cells activation in CRLM. Clinically, increased infiltration of IgG+ plasma cells and macrophages in HCC was correlated to worse survival, while increased intratumoral IgA+ plasma cells and neutrophils in CRLM indicated poor prognosis. Taken together, this study demonstrated plasma and myeloid cell-mediated immunosuppression in HCC and CRLM, suggesting that selectively modulating primary or secondary tumor-related immunosuppressive regulatory networks might reprogram the microenvironment and provide an immunotherapeutic strategy for treating liver cancer.
2023-06-19 | GSE235057 | GEO
Project description:Collagen, a major component of the extracellular matrix, is significantly upregulated in colorectal liver metastasis (CRLM) compared to liver tissue. Expression levels of specific collagen types in CRLM resemble those in colorectal cancer (CRC) and colon tissue. We investigated whether the collagen hydroxylation pattern from the primary tumor also migrates with the metastatic tumor. The degree of collagen alpha-1(I) hydroxylation in colon, CRC, liver, and CRLM tissue in the same individuals (n=14) was studied with mass spectrometry. The degree of hydroxylation was investigated in 36 collagen alpha-1(I) peptides, which covered 54% of the triple helical region. The average degree of hydroxylation in liver tissue was similar to that in colon tissue. The overall degree of hydroxylation was significantly lower (9% +/- 14%) in CRC tissue and also significantly lower (12% +/-22%) in CRLM tissue compared to colon or liver tissue. Still, in previous research of liver and CRLM enzymes involved in collagen hydroxylation were found to be upregulated, whereas P4HB (4-prolyl hydroxylase beta unit) was downregulated. Furthermore, 11 peptides are present with a specific number of hydroxylations that are significantly different between CRLM and liver tissue; these peptides could be candidates for the detection of CRLM. For one of these eleven peptides, a matching naturally occurring peptide in urine has been identified as being significantly different between patients suffering from CRLM and healthy controls. We conclude that the degree of hydroxylation in CRC and CRLM tumor tissue is in general significantly downregulated in comparison to healthy colon and liver tissue. The hydroxylation pattern in CRLM resemble partly the pattern in liver, primary colorectal cancer and colon.
2020-09-16 | PXD015015 | Pride
Project description:Purpose: Our research aims to identify the expression, clinical value, biological significance and signaling pathway of KIAA1522 in colorectal carcinoma liver metastases (CRLM). Materials and Methods: To elucidate the role of KIAA1522 in CRC, its expression and survival analysis were assessed using GEPIA databases. Then we evaluated expression of KIAA1522 immunohistochemically in tissue samples of 57 patients with CRLM. The correlations between expression of KIAA1522 and clinical significance, prognosis of these 57 patients with CRLM were analyzed. Western blotting, CCK-8, colony formation, Flow cytometry, Transwell invasion, and wound healing assays were performed to explore the function of KIAA1522 in colon cancer cell lines. Finally, transcriptome sequencing and gene set enrichment analysis was used to identify the pathways involved. Results: Our results demonstrated that KIAA1522 was highly expressed in CRLM tissues and colon cancer cell lines, and expression of KIAA1522 in primary sites was significantly positively correlated with that in metastatic sites. Furthermore, KIAA1522 overexpression was associated with unfavorable clinicopathological characteristics. Survival analyses revealed that KIAA1522 overexpression predicted lower overall survival rates in patients with CRLM. Functional studies suggested that KIAA1522 facilitated proliferation, migration and invasion of colon cancer cell lines in vitro. Moreover, KIAA1522 upregulated the Notch signaling pathway, as confirmed by transcriptome sequencing and gene set enrichment analysis. Conclusion: In conclusion, these data suggest that upregulation of KIAA1522 might enhance tumorigenicity and metastasis of colon cancer cell lines through potentiating the Notch signaling pathway activity. Expression of KIAA1522 plays oncogenic roles in CRLM and might serve as a novel molecular target in CRLM treatment.
2022-12-31 | GSE174449 | GEO
Project description:Background The molecular mechanisms underlying colon cancer development are multifactorial. There is a clinical need for better markers than current TNM stages for stratifying risk of recurrent disease and to guide clinicians in choice of adjuvant treatment. The objective of this study is to evaluate the level of differences between recurrent and non-recurrent colon cancer in five year follow-up by proteomics. We identified 4,805 proteins quantified across all ten groups with at least one unique peptide sequence and 1% FDR. For the cluster analysis, 2919 proteins (61%) appear in two clusters differentiating the tumor and control samples. 54 proteins (1 %) appear in a cluster seemingly differentiating recurrent and non-recurrent cancer. A cut-off strategy with pathway analysis identify 255 proteins (5%) different between recurrent and non-recurrent cancer for the combined TNM2 and TNM3 group. Likewise, we identified 727 proteins (15%) for the TNM2 r+/r- group and 343 proteins (7%) for TNM3 r+/r-, partly with overlapping predicted gene findings. We demonstrate the degree of dissimilarity between recurrent and nonrecurrent cancer in a proteomics dataset. We believe these findings are usable for setting up larger scale experiments in recurrent cancer although the study is underpowered for diagnostic purposes.
2022-03-11 | PXD026630 | Pride