RCC1 Expression as a Prognostic Marker in Colorectal Liver Oligometastases.
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ABSTRACT:
SUBMITTER: Deng Y
PROVIDER: S-EPMC8674189 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe aim of this study was to assess trophoblast antigen protein 2 (TROP2) expression in liver oligometastases and its prognostic value for colorectal liver oligometastasis (CLO) patients undergoing liver resection.MethodsWe retrospectively selected 129 consecutive CLO patients who underwent curative liver resection between June 1999 and December 2016. Immunohistochemistry (IHC) was performed to detect TROP2 expression in paraffin-embedded specimens. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and log-rank test, and independent prognostic factors were identified with Cox regression modeling.ResultsTROP2 was expressed in 72.9% (94/129) of liver oligometastatic tissues. TROP2 expression in primary tumors and liver oligometastases was significantly positively correlated (r = 0.758, p < 0.001). Survival analysis indicated that CLO patients with high TROP2 expression had worse 3-year RFS (44.2% versus 66.4%, p = 0.007) and 3-year OS rates (70.3% versus 85.4%, p = 0.035) than did those with low TROP2 expression. Multivariate analysis indicated that high TROP2 expression was independently associated with poor RFS [hazard ratio (HR) = 2.017; 95% confidence interval (CI) 1.198-3.396; p = 0.023] and OS (HR = 2.090; 95% CI 1.037-4.214; p = 0.039). Gene expression profile analysis indicated that high TROP2 expression was associated with TNFα signaling via NF-κB, the inflammatory response and epithelial-mesenchymal transition (EMT).ConclusionsTROP2 overexpression was associated with an unfavorable oncologic prognosis in patients with CLO undergoing liver resection. Detecting TROP2 expression may be valuable for guiding postoperative treatment among CLO patients.
| S-EPMC8842308 | biostudies-literature
Project description:PurposePrognostic schemes that rely on clinical variables to predict outcome after resection of colorectal metastases remain imperfect. We hypothesized that molecular markers can improve the accuracy of prognostic schemes.MethodsWe screened the transcriptome of matched colorectal liver metastases (CRCLM) and primary tumors from 42 patients with unresected CRCLM to identify differentially expressed genes. Among the differentially expressed genes identified, we looked for associations between expression and time to disease progression or overall survival. To validate such associations, mRNA levels of the candidate genes were assayed by qRT-PCR from CRCLM in 56 additional patients who underwent hepatectomy.ResultsSeven candidate genes were selected for validation based on their differential expression between metastases and primary tumors and a correlation between expression and surgical outcome: lumican; tissue inhibitor metalloproteinase 1; basic helix-loop-helix domain containing class B2; fibronectin; transmembrane 4 superfamily member 1; mitogen inducible gene 6 (MIG-6); and serpine 2. In the hepatectomy group, only MIG-6 expression was predictive of poor survival after hepatectomy. Quantitative PCR of MIG-6 mRNA was performed on 25 additional hepatectomy patients to determine if MIG-6 expression could substratify patients beyond the clinical risk score. Patients within defined clinical risk score categories were effectively substratified into distinct groups by relative MIG-6 expression.ConclusionsMIG-6 expression is inversely associated with survival after hepatectomy and may be used to improve traditional prognostic schemes that rely on clinicopathologic data such as the Clinical Risk Score.
| S-EPMC6328378 | biostudies-literature
Project description:UnlabelledIntegrins are cell surface adhesion molecules (CAM) that regulate via intercellular and cell-matrix signaling various cellular processes including wound healing, cell differentiation, division, growth, migration and metastatic dissemination. Although a correlation between carcinogenesis and changes in integrin expression, especially ?1 integrin, has been reported, its role in colorectal liver metastases remains unclear. This study aimed to evaluate the expression of ?1 integrin in colorectal liver metastases and to correlate the pattern of expression with clinicopathological features and to investigate the putative role of ?1 integrin expression on survival of these patients.MethodsFormalin-fixed, paraffin-embedded (FFPE) tumor samples of 81 patients who were operated because of colorectal liver metastases without any neoadjuvant therapy were obtained and stained with hematoxylin and eosin (H & E). An immunohistochemical examination was performed using Dako, Peroxidase/DAB kit and a primary monoclonal ?1 integrin (CD29, fibronectin receptor subunit beta; ab3167, Abcam plc). ?1 integrin expression was evaluated according to the immunoreactive score of Remmele and Stegner and was related with clinicopathological features of prognostic significance and with disease-free and overall survival as well. Statistical analysis was performed using SPSS version 21.0.Results?1 integrin was overexpressed in tumor cells in 37 (48%) patients and in stromal cell in 27 (33%) patients. The ?1 expression was not statistically correlated with clinicopathological features of the primary tumors but it was statistically correlated (p=0.03) with the histological grading of liver metastases. Kaplan-Meier survival analysis showed that there is a tendency but no statistically significant correlation in disease-free and overall survival.ConclusionConsidering that expression of ?1 integrin in colorectal liver metastases remains controversial, specially its relation with survival of patients, we showed that the ?1 expression represents a reliable prognostic factor regarding the grading of liver metastases of CRC and our findings imply that ?1 integrin expression profiles may have further potential in identifying the stage of colorectal liver metastases and being a marker of prognosis in these patients.
| S-EPMC3885484 | biostudies-literature
Project description:Colon cancer cells have previously been demonstrated to contain a subpopulation of CD133+ tumour cells that have the ability to initiate tumour growth and are thus referred to as colon cancer-initiating cells or colon cancer stem cells (CSCs). As CD133 is currently one of the best markers to characterise colon CSCs, we analysed CD133+ tumour cells in colorectal cancer specimens using immunohistochemistry. We show that CD133 detection is specific and that the CD133 antigen is localised on the glandular-luminal surface of colon cancer cells, whereas undifferentiated tumour cells at the front of invasion are CD133-. In addition, CD133+ cells are characterised in situ by lack of CK20 expression, whereas they are positive for EpCAM. Moreover, we show that CD133 expression in colorectal cancer is an independent prognostic marker that correlates with low survival in a stratified patient collective. Our results indicate that in colorectal cancer, the CD133+ tumour cells can be detected by immunohistochemistry, which facilitates their further characterisation in situ.
| S-EPMC2570510 | biostudies-literature
Project description:Immune checkpoint blockade has not yet been effective in patients with mismatch repair proficient metastatic colorectal cancer. Targeting immunosuppressive metabolic pathways is being explored as a new immunotherapeutic approach. We assessed whether CD73, the rate limiting enzyme that catalyzes the degradation of extracellular AMP into immunosuppressive adenosine, could be an immunological determinant of colorectal liver metastases (CRLMs). By immunofluorescence on tissue microarrays, intratumoral CD73 expression (tCD73) was analyzed in 391 CRLMs resected in 215 patients, and soluble CD73 (sCD73) was measured by ELISA in the pre-operative serum of 193 patients. High tCD73 was associated with worse pathological features, such as multiple and larger CRLMs, and poorer pathologic response to pre-operative chemotherapy. The median time to recurrence and disease-specific survival after CRLM resection was significantly shorter in patients with high tCD73 (11.0 and 46.4 months, respectively) compared with low tCD73 (19.0 and 61.5 months, respectively). tCD73 was strongly associated with patient outcomes independently of clinicopathological variables. sCD73 did not correlate with tCD73. Patients with high levels of sCD73 also had shorter disease-specific survival. Our results suggested that CD73 in CRLMs may be prognostically informative and may help select patients more likely to respond to adenosine pathway blocking agents.
| S-EPMC7185220 | biostudies-literature
Project description:The goal of this study was to determine the frequency of HLA class II antigen expression in colorectal carcinoma (CRC) tumors, its association with the clinical course of the disease, and the underlying mechanism(s). Two tissue microarrays constructed with 220 and 778 CRC tumors were stained with HLA-DR, DQ, and DP antigen-specific monoclonal antibody LGII-612.14, using the immunoperoxidase staining technique. The immunohistochemical staining results were correlated with the clinical course of the disease. The functional role of HLA class II antigens expressed on CRC cells was analyzed by investigating their in vitro interactions with immune cells. HLA class II antigens were expressed in about 25% of the 220 and 21% of the 778 tumors analyzed with an overall frequency of 23%. HLA class II antigens were detected in 19% of colorectal adenomas. Importantly, the percentage of stained cells and the staining intensity were significantly lower than those detected in CRC tumors. However, HLA class II antigen staining was weakly detected only in 5.4% of 37 normal mucosa tissues. HLA class II antigen expression was associated with a favorable clinical course of the disease. In vitro stimulation with interferon gamma (IFNγ) induced HLA class II antigen expression on two of the four CRC cell lines tested. HLA class II antigen expression on CRC cells triggered interleukin-1β (IL-1β) production by resting monocytes. HLA class II antigen expression in CRC tumors is a favorable prognostic marker. This association may reflect stimulation of IL-1β production by monocytes.
| S-EPMC3924546 | biostudies-literature
Project description:Patients with colorectal liver metastasis (CLM) present with heterogenous clinical outcomes and improved classification is needed to ameliorate the therapeutic output. Macrophages (Mϕ) hold promise as prognostic classifiers and therapeutic targets. Here, stemming from a single-cell analysis of mononuclear phagocytes infiltrating human CLM, we identified two Mϕ markers associated with distinct populations with opposite clinical relevance. The invasive margin of CLM was enriched in pro-inflammatory monocyte-derived Mϕ (MoMϕ) expressing the monocytic marker SERPINB2, and a more differentiated population, tumor-associated Mϕ (TAM), expressing glycoprotein nonmetastatic melanoma protein B (GPNMB). SERPINB2+ MoMϕ had an early inflammatory profile, whereas GPNMB+ TAMs were enriched in pathways of matrix degradation, angiogenesis, and lipid metabolism and were found closer to the tumor margin, as confirmed by spatial transcriptomics on CLM specimens. In a cohort of patients, a high infiltration of SERPINB2+ cells independently associated with longer disease-free survival (DFS; P = 0.033), whereas a high density of GPNMB+ cells correlated with shorter DFS (P = 0.012) and overall survival (P = 0.002). Cell-cell interaction analysis defined opposing roles for MoMϕ and TAMs, suggesting that SERPINB2+ and GPNMB+ cells are discrete populations of Mϕ and may be exploited for further translation to an immune-based stratification tool. This study provides evidence of how multi-omics approaches can identify nonredundant, clinically relevant markers for further translation to immune-based patient stratification tools and therapeutic targets. GPNMB has been shown to set Mϕ in an immunosuppressive mode. Our high dimensional analyses provide further evidence that GPNMB is a negative prognostic indicator and a potential player in the protumor function of Mϕ populations.
| S-EPMC10070171 | biostudies-literature
Project description:BackgroundColorectal cancer (CRC) is one of the most malignant gastrointestinal cancers worldwide. The liver is the most important metastatic target organ, and liver metastasis is the leading cause of death in patients with CRC. Owing to the lack of sensitive biomarkers and unclear molecular mechanism, the occurrence of liver metastases cannot be predicted and the clinical outcomes are bad for liver metastases. Therefore, it is very important to identify the diagnostic or prognostic markers for liver metastases of CRC.AimTo investigate the highly differentially expressed genes (HDEGs) and prognostic marker for liver metastases of CRC.MethodsData from three NCBI Gene Expression Omnibus (GEO) datasets were used to show HDEGs between liver metastases of CRC and tumour or normal samples. These significantly HDEGs of the three GEO datasets take the interactions. And these genes were screened through an online tool to explore the prognostic value. Then, TIMER and R package were utilized to investigate the immunity functions of the HDEGs and gene set enrichment analysis was used to explore their potential functions.ResultsBased on the selection criteria, three CRC datasets for exploration (GSE14297, GSE41258, and GSE49355) were chosen. Venn diagrams were used to show HDEGs common to the six groups and 47 HDEGs were obtained. The HDEGs were shown by using STRING and Cytoscape software. Based on the TCGA database, APOC1 showed significantly different expression between N2 and N0, and N2 and N1. And there was also a significant difference in expression between T2 and T4, and between T2 and T3. In 20 paired CRC and normal tissues, quantitative real-time polymerase chain reaction illustrated that the APOC1 mRNA was strongly upregulated in CRC tissues (P = 0.014). PrognoScan and GEPIA2 revealed the prognostic value of APOC1 for overall survival and disease-free survival in CRC (P < 0.05). TIMER showed that APOC1 has a close relationship with immune infiltration (P < 0.05).ConclusionAPOC1 is a biomarker that is associated with both the diagnosis and prognosis of liver metastases of CRC.
| S-EPMC8180235 | biostudies-literature
Project description:BACKGROUND: Colorectal cancer can be efficiently treated when found at early stages, thus the search for novel markers is of paramount importance. Since inflammation is associated with cancer progression and angiogenesis, we investigated expression of cytokines like IL-6 and other mediators that play a key role in the innate immune system, in particular toll like receptor 4 (TLR4), in the microenvironment of lesions from different stages of colon disease progression, from ulcerative colitis to adenoma and adenocarcinoma to find useful markers. METHODS: The presence of inflammatory cells and expression of key cytokines involved in the inflammation process were quantified by immunohistochemistry in specific tissue compartments (epithelial, stromal, endothelial) by immunohistochemistry. A murine azoxymethane/dextran sulfate model in which Tir8, a negative regulator of the inflammatory response, was ablated was used to confirm the clinical observations. 116 Archival tissue samples from patients with different stages of colorectal disease: 13 cases of ulcerative colitis (UC), 34 tubular or tubulo-villous adenomas (AD), and 53 infiltrating adenocarcinomas. 16 specimens of healthy mucosa surgically removed with the cancerous tissue were used as a control. RESULTS: The differences between healthy tissues and the diverse lesions was characterized by a marked inflammatory-angiogenic reaction, with significantly (P < 0.05) higher numbers of CD68, CD15, and CD31 expressing cells in all diseased tissues that correlated with increasing grade of malignancy. We noted down-regulation of a potential modulator molecule, Hepatocyte Growth Factor, in all diseased tissues (P < 0.05). TLR-4 and IL6 expression in the tumor microenvironment were associated with adenocarcinoma in human samples and in the murine model. We found that adenocarcinoma patients (pT1-4) with higher TLR-4 expression in stromal compartment had a significantly increased risk in disease progression. In those patients with a diagnosis of pT3 (33 cases) colon cancer, those with very high levels of TLR-4 in the tumor stroma relapsed significantly earlier than those with lower expression levels. CONCLUSIONS: These data suggest that high TLR-4 expression in the tumor microenvironment represents a possible marker of disease progression in colon cancer.
| S-EPMC2997091 | biostudies-literature
Project description:PurposePatients with oligometastatic colorectal cancer have demonstrated excellent clinical outcomes with surgical resection of hepatic and pulmonary metastases. Stereotactic ablative radiation therapy (SABR) has emerged as an alternative local therapy for nonsurgical candidates. Herein, we report the oncologic and patient-reported quality-of-life (PR-QoL) outcomes for a subset of patients with oligometastatic colorectal cancer who were treated in a prospective phase 2 multicenter clinical trial.Methods and materialsPatients with a pathologically proven diagnosis of oligometastatic colorectal cancer were enrolled as part of a prospective study. SABR dose and fractionation schedules were dependent on the lesion location and size. Patient follow-up occurred 6 weeks after completion of SABR and at 3-month intervals for the following 3 years. Patients received the Functional Assessment of Cancer Therapy-General questionnaire at baseline and at each follow-up visit to assess PR-QoL. The total Functional Assessment of Cancer Therapy-General questionnaire scores were compared with those from baseline using the Wilcoxon signed rank test. Overall survival, local progression-free survival (PFS), and distant PFS were calculated using the Kaplan-Meier estimation to the date of the last follow-up visit/death or local/distant failure.ResultsA total of 31 patients with oligometastatic colorectal cancer with 1 (71.0%), 2 (16.1%), 3 (3.2%), 4 (3.2%), or 5 (6.5%) metastatic lesions were identified. After a median follow-up time of 50.1 months, the median OS from the time of completion of the SABR was 53.9 months (95% confidence interval, 23.2-84.6), and the 5-year OS, local PFS, and distant PFS were 45%, 83%, and 27%, respectively. Acute grade 2+ toxicity was 9.7% (pain, nausea, fatigue) and late grade 3+ toxicity (small bowel obstruction) was 3.2% with no significant change in PR-QoL in the year after SABR.ConclusionsThis subset analysis of a prospective phase 2 study demonstrates that SABR is a safe and effective treatment option for patients with unresectable oligometastic colorectal cancer. In addition, SABR of oligometastatic disease preserves PR-QoL.
| S-EPMC6349603 | biostudies-literature