The role of ccr5 polymorphism in colorectal cancer and liver metastasis in the Tunisian population

Chemokines and their receptors are involved in cancer initiation and progression, including colorectal cancer (CRC) and liver metastasis formation. Our aim was to elucidate C-C chemokine receptor type 5 (CCR5) gene polymorphism (CCR5?32) impact on CRC and colorectal cancer liver metastases (CRLM) occurrence risk. We analyzed the CCR5 gene mutational status in 108 primary CRC cases, 35 CRLM and 248 healthy individuals, and evaluated CCR5 expression in healthy tissue and tumors. Rare allele ??32? was more frequent in controls (7.2% vs 2.8% in CRC). All 35 metastases had wild-type CCR5. Our analysis showed that CCR5 wild type has a significant risk of 2.73-fold (95% CI=1.22-7.31) to cause CRC while ?32 reduced the risks 0.36-fold (95% CI=0.13-0.82). For CRC, CCR5 correlated with left-sided tumors and liver metastases (P=0.040 and P= 0.039 respectively). As for CRLM, no correlation was found. Immunohistochemical profile analysis of CCR5 revealed a significant association with the male gender (P=0.049) and non-mucinous carcinomas (P< 0.001) in primary CRC. CCR5 expression revealed an association with the degree of tumor differentiation for both CRC and CRLM (P < 0.001). CCR5?32 might be a protective factor against CRC development and dissemination.

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Estrogen as a prognostic factor on liver metastasis from colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.506 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 506-506

Author(s):

Sen Zhang ◽

Zhen Hua He ◽

Xue Lei Zhang ◽

Zhen Jie Wu ◽

Jun Ouyang

Keyword(s):

Colorectal Cancer ◽

Liver Metastasis ◽

Liver Metastases ◽

Survival Time ◽

Protective Factor ◽

Pearson Correlation ◽

Survival Rates ◽

Prognostic Impact ◽

Synchronous Liver Metastases ◽

Normal Tissues

506 Background: Estrogen plays an important role in some cancer. However, previous studies about the influence of estrogen on colorectal cancer (CRC) have been conflicting, especially rare reports on liver metastasis. This study tries to explore the prognostic impact of estrogen on CRC with liver metastasis. Methods: Eighty six patients with CRC including 43 synchronous liver metastases were studied. Estrogen receptor-beta (ER-beta) were assayed by immunohistochemistry (IHC) in liver metastasis tissues, colorectal cancer tissues and normal tissues. And the serum estrogens were detected by radioimmunoassay (RIA) in 30 patients with CRC including 14 synchronous liver metastases. After follow-up, the relationship between ERβ, estrogen and survival time were analyzed. Results: The positive rates of ER-beta in liver metastases tissues, CRC tissues and normal tissues were 39.5% (17/43), 39.5% (34/86) and 62.8% (54/86), respectively; and significant differences were found between liver metastasis (P=0.012) or CRC (P=0.002) with normal tissues. The 1-, 2-, 3-and 5-year survival rates for ER-beta positive patients were 97%, 79%, 71% and 51%, respectively comparing with 82%, 59%, 55% and 40%, respectively for ER-beta negative patients (P=0.190). In contrast, the 1-, 2-, 3- and 5-year survival rates in liver metastasis group were 77%, 37%, 31% and 23%, respectively; and 93%, 64%, 57% and 57%, respectively for ER-beta positive patients comparing with 67%, 19%, 14% and 7%, respectively for ER-beta negative patients (P=0.004). Serum estrogen levels in patients with liver metastases were significantly lower than those without liver metastasis (P=0.012) and Pearson Correlation showed that there was a moderate positive correlation between level of serum estrogen and survival time (P=0.006). Conclusions: CRC liver metastasis patients with positive ER-beta have a better survival, which indicates estrogen is a protective factor for CRC liver metastasis patients. But more study is needed to show estrogen would be a protective factor for CRC patients.

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Heterogeneity of KRAS, NRAS, PIK3CA and BRAF mutational status in primary tumour, lymph nodes and liver metastases in sporadic colorectal cancer

10.26226/morressier.5b4709896f4cb30010951e82 ◽

2018 ◽

Author(s):

Sofia Del Carmen

Keyword(s):

Colorectal Cancer ◽

Lymph Nodes ◽

Liver Metastases ◽

Primary Tumour ◽

Sporadic Colorectal Cancer ◽

Mutational Status

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Evidence-Based Second-Line Treatment in RAS Wild-Type/Mutated Metastatic Colorectal Cancer in the Precision Medicine Era

International Journal of Molecular Sciences ◽

10.3390/ijms22147717 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7717

Author(s):

Guido Giordano ◽

Pietro Parcesepe ◽

Giuseppina Bruno ◽

Annamaria Piscazzi ◽

Vincenzo Lizzi ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Checkpoint Inhibitors ◽

Line Treatment ◽

Second Line ◽

Wild Type ◽

First Line ◽

Braf Mutations ◽

Mutational Status ◽

First Line Treatment

Target-oriented agents improve metastatic colorectal cancer (mCRC) survival in combination with chemotherapy. However, the majority of patients experience disease progression after first-line treatment and are eligible for second-line approaches. In such a context, antiangiogenic and anti-Epidermal Growth Factor Receptor (EGFR) agents as well as immune checkpoint inhibitors have been approved as second-line options, and RAS and BRAF mutations and microsatellite status represent the molecular drivers that guide therapeutic choices. Patients harboring K- and N-RAS mutations are not eligible for anti-EGFR treatments, and bevacizumab is the only antiangiogenic agent that improves survival in combination with chemotherapy in first-line, regardless of RAS mutational status. Thus, the choice of an appropriate therapy after the progression to a bevacizumab or an EGFR-based first-line treatment should be evaluated according to the patient and disease characteristics and treatment aims. The continuation of bevacizumab beyond progression or its substitution with another anti-angiogenic agents has been shown to increase survival, whereas anti-EGFR monoclonals represent an option in RAS wild-type patients. In addition, specific molecular subgroups, such as BRAF-mutated and Microsatellite Instability-High (MSI-H) mCRCs represent aggressive malignancies that are poorly responsive to standard therapies and deserve targeted approaches. This review provides a critical overview about the state of the art in mCRC second-line treatment and discusses sequential strategies according to key molecular biomarkers.

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Yttrium-90 radioembolization for colorectal cancer liver metastases in KRAS wild-type and mutant patients: Clinical and ccfDNA studies

Oncology Reports ◽

10.3892/or.2016.5284 ◽

2016 ◽

Vol 37 (1) ◽

pp. 57-65 ◽

Cited By ~ 10

Author(s):

E. Janowski ◽

O. Timofeeva ◽

S. Chasovskikh ◽

M. Goldberg ◽

A. Kim ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastases ◽

Wild Type ◽

Colorectal Cancer Liver Metastases ◽

Yttrium 90

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Evaluation of Histopathological Heterogeneity After Preoperative Chemotherapy in Patients With Liver Metastases from Colorectal Cancer

10.21203/rs.3.rs-192547/v1 ◽

2021 ◽

Author(s):

Nobuhisa matsuhashi ◽

Hiroyuki Tomita ◽

Takazumi Kato ◽

Yoshinori Iwata ◽

Satoshi Matsui ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastasis ◽

Liver Metastases ◽

Surgical Oncology ◽

Resected Specimen ◽

Histopathological Changes ◽

School Of Medicine ◽

Response To Chemotherapy ◽

Grade 3 ◽

The Right

Abstract Background: Patients with liver metastases from colorectal cancer (CRLMs) frequently receive chemotherapy prior to liver resection. Histopathological assessment of the resected specimen can evaluate the response to chemotherapy. This study analyzed the correlation between histopathological changes in the primary site and liver metastases. Patients and Methods: This study comprised 45 patients with resectable CRLMs at the Surgical Oncology Department of Gifu University School of Medicine from January 2006 to August 2015. Results: The study included 24 men and 21 women. The primary colonic tumor was located in the right side in 13 (28.9%) patients and the left side in 32 (71.9%) patients. We evaluated patients with metastatic colorectal cancer (31/45) after excluding those in whom histopathological heterogeneity between the primary and liver metastasis changed to grade 3 after chemotherapy. We compared the group which underwent hepatectomy after chemotherapy (n=25) with that underwent hepatectomy alone (n=6). In 16 (53.3%) out of 25 patients, histopathological heterogeneity of the liver metastasis was lost (p=0.04). Conclusion: Chemotherapy appears to change histopathological heterogeneity.Our study suggests that the change of intratumoral heterogeneity reflect by the response of chemotherapy.

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Genome-Wide Scan for Copy Number Alteration Association with Relapse-Free Survival in Colorectal Cancer with Liver Metastasis Patients

Journal of Clinical Medicine ◽

10.3390/jcm7110446 ◽

2018 ◽

Vol 7 (11) ◽

pp. 446 ◽

Cited By ~ 1

Author(s):

Po-Sheng Yang ◽

Hsi-Hsien Hsu ◽

Tzu-Chi Hsu ◽

Ming-Jen Chen ◽

Cin-Di Wang ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastasis ◽

Liver Metastases ◽

Copy Number ◽

Copy Number Alteration ◽

Gene Signature ◽

Comparative Genomic ◽

Relapse Free Survival ◽

Cgh Array ◽

Free Survival

Predicting a patient’s risk of recurrence after the resection of liver metastases from colorectal cancer is critical for evaluating and selecting therapeutic approaches. Clinical and pathologic parameters have shown limited accuracy thus far. Therefore, we combined the clinical status with a genomic approach to stratify relapse-free survival in colorectal cancer liver metastases patients. To identify new molecular and genetic signatures specific to colorectal cancer with liver metastasis (CRCLM) patients, we conducted DNA copy number profiling on a cohort of 21 Taiwanese CRCLM patients using a comparative genomic hybridization (CGH) array. We identified a three-gene signature based on differential copy number alteration between patients with different statuses of (1) recurrence and (2) synchronous metastasis. In relapse hotspot regions, only three genes (S100PBP, CSMD2, and TGFBI) were significantly associated with the synchronous liver metastasis factor. A final set of three genes—S100PBP, CSMD2, TGFBI—significantly predicted relapse-free survival in our cohort (p = 0.04) and another CRCLM cohort (p = 0.02). This three-gene signature is the first genomic signature validated for relapse-free survival in post-hepatectomy CRCLM patients. Our three-gene signature was developed using a whole-genome CGH array and has a good prognostic position for the relapse-free survival of CRCLM patients after hepatectomy.

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Nkx2.5 Functions as a Conditional Tumor Suppressor Gene in Colorectal Cancer Cells via Acting as a Transcriptional Coactivator in p53-Mediated p21 Expression

Frontiers in Oncology ◽

10.3389/fonc.2021.648045 ◽

2021 ◽

Vol 11 ◽

Author(s):

Huili Li ◽

Jiliang Wang ◽

Kun Huang ◽

Tao Zhang ◽

Lu Gao ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Expression Pattern ◽

Cell Lines ◽

Suppressor Gene ◽

Transcriptional Coactivator ◽

Wild Type ◽

Mutational Status ◽

Sw480 Cells

NK2 homeobox 5 (Nkx2.5), a homeobox-containing transcription factor, is associated with a spectrum of congenital heart diseases. Recently, Nkx2.5 was also found to be differentially expressed in several kinds of tumors. In colorectal cancer (CRC) tissue and cells, hypermethylation of Nkx2.5 was observed. However, the roles of Nkx2.5 in CRC cells have not been fully elucidated. In the present study, we assessed the relationship between Nkx2.5 and CRC by analyzing the expression pattern of Nkx2.5 in CRC samples and the adjacent normal colonic mucosa (NCM) samples, as well as in CRC cell lines. We found higher expression of Nkx2.5 in CRC compared with NCM samples. CRC cell lines with poorer differentiation also had higher expression of Nkx2.5. Although this expression pattern makes Nkx2.5 seem like an oncogene, in vitro and in vivo tumor suppressive effects of Nkx2.5 were detected in HCT116 cells by establishing Nkx2.5-overexpressed CRC cells. However, Nkx2.5 overexpression was incapacitated in SW480 cells. To further assess the mechanism, different expression levels and mutational status of p53 were observed in HCT116 and SW480 cells. The expression of p21WAF1/CIP1, a downstream antitumor effector of p53, in CRC cells depends on both expression level and mutational status of p53. Overexpressed Nkx2.5 could elevate the expression of p21WAF1/CIP1 only in CRC cells with wild-type p53 (HCT116), rather than in CRC cells with mutated p53 (SW480). Mechanistically, Nkx2.5 could interact with p53 and increase the transcription of p21WAF1/CIP1 without affecting the expression of p53. In conclusion, our findings demonstrate that Nkx2.5 could act as a conditional tumor suppressor gene in CRC cells with respect to the mutational status of p53. The tumor suppressive effect of Nkx2.5 could be mediated by its role as a transcriptional coactivator in wild-type p53-mediated p21WAF1/CIP1 expression.

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A grading system for predicting the prognosis of gastric cancer with liver metastasis

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyab140 ◽

2021 ◽

Author(s):

Soshi Hori ◽

Michitaka Honda ◽

Hiroshi Kobayashi ◽

Hidetaka Kawamura ◽

Koichi Takiguchi ◽

...

Keyword(s):

Colorectal Cancer ◽

Gastric Cancer ◽

Overall Survival ◽

Liver Metastasis ◽

Confidence Interval ◽

Liver Metastases ◽

Hazard Ratio ◽

Maximum Diameter ◽

Grading System ◽

Computed Tomography Images

Abstract Objective The prognosis of patients with liver metastases from gastric cancer is determined using tumor size and number of metastases; this is similar to the factors used for the prediction of liver metastases from colorectal cancer. The relationship between the degree of liver metastasis from gastric cancer and prognosis with reference to the classification of liver metastasis from colorectal cancer was investigated. Methods This was a multi-institutional historical cohort study. Among patients with stage IV gastric cancer, who visited the cancer hospitals in Fukushima Prefecture, Japan, between 2008 and 2015, those with simultaneous liver metastasis were included. Abdominal pretreatment computed tomography images were reviewed and classified into H1 (four or less liver metastases with a maximum diameter of ≤5 cm); H2 (other than H1 and H3) or H3 (five or more liver metastases with a maximum diameter of ≥5 cm). The hazard ratio for overall survival according to the H grade (H1, H2 and H3) was calculated using the Cox proportional hazards model. Results A total of 412 patients were analyzed. Patients with H1, H2 and H3 grades were 118, 162 and 141, respectively, and their median survival time was 10.2, 5.7 and 3.1 months, respectively (log-rank P < 0.001). The adjusted hazard ratio for overall survival was H1: H2: H3 = reference: 1.39 (95% confidence interval: 1.04–1.85): 1.69 (95% confidence interval: 1.27–2.27). Conclusions The grading system proposed in this study was a simple and easy-to-use prognosis prediction index for patients with liver metastasis from gastric cancer.

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