Dataset Information

Epithelial expression of FHL2 is negatively associated with metastasis-free and overall survival in colorectal cancer.

ABSTRACT:

Background

Four-and-a-half LIM domains protein 2 (FHL2) is a component of the focal adhesion structures and has been suggested to have a role in cancer progression. It has been shown to be overexpressed in the colorectal cancer (CRC).

Methods

Here, we examined a possible prognostic value of FHL2 in CRC. Immunohistochemistry for FHL2 was performed on 296 CRCs without distant metastases at the time of surgery. Staining in the epithelial compartment was quantitatively evaluated using image analysis, and results were related to clinical variables. Antibody specificity was tested using small-interfering RNA transfection in hTERT-immortalised myofibroblasts.

Results

Varying degrees of cytoplasmic FHL2 expression by neoplastic epithelial cells were detectable in all cases. Higher FHL2 expression in the epithelial compartment was an independent adverse prognostic factor. Multivariate Cox analysis shows that expression in the tumour invasion front (P<0.001) as well as in the centre of the tumour (P<0.001) was associated with metachronous metastases independently of the clinicopathological variables; expression in the tumour invasion front was also associated with overall survival independently of the clinicopathological variables (P<0.01).

Conclusion

Higher FHL2 expression is involved in CRC progression and correlates with the development of metachronous metastases and overall survival, suggesting that FHL2 is an independent adverse prognostic indicator for CRC.

SUBMITTER: Verset L

PROVIDER: S-EPMC3708555 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Publications

Epithelial expression of FHL2 is negatively associated with metastasis-free and overall survival in colorectal cancer.

Verset L L Tommelein J J Moles Lopez X X Decaestecker C C Mareel M M Bracke M M Salmon I I De Wever O O Demetter P P

British journal of cancer 20130611 1

<h4>Background</h4>Four-and-a-half LIM domains protein 2 (FHL2) is a component of the focal adhesion structures and has been suggested to have a role in cancer progression. It has been shown to be overexpressed in the colorectal cancer (CRC).<h4>Methods</h4>Here, we examined a possible prognostic value of FHL2 in CRC. Immunohistochemistry for FHL2 was performed on 296 CRCs without distant metastases at the time of surgery. Staining in the epithelial compartment was quantitatively evaluated using ...[more]

PMID: 23756870

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Project description:BackgroundMetastatic colorectal cancer (mCRC) is a highly heterogeneous disease from a clinical, molecular, and immunological perspective. Current predictive models rely primarily in tissue based genetic analysis, which not always correlate with inflammatory response. Here we evaluated the role of a circulating inflammatory signature as a prognostic marker in mCRC.MethodsTwo hundred eleven newly diagnosed patients with mCRC were enrolled in the study. One hundred twenty-one patients had unresectable metastases, whereas ninety patients had potentially resectable liver metastases at presentation. Analysis of miR-21, IL-6, and IL-8 in the plasma of peripheral blood was performed at baseline. Patients with high circulating levels of ≥2 of the three inflammation markers (miR-21, IL-6, and IL-8) were considered to have the "Inflammation phenotype-positive CISIG".ResultsPositive CISIG was found in 39/90 (43%) and 50/121 (45%) patients in the resectable and unresectable cohort, respectively. In the resectable population the median relapse-free survival was 18.4 compared to 31.4 months (p = 0.001 HR 2.09, 95% CI 1.2-3.67) for positive vs. negative CISIG. In contrast, the individual components were not significant. In the same population the median overall survival was 46.2 compared to 66.0 months (p = 0.0003, HR 2.57, 95% CI 1.26-5.27) for positive vs. negative CISIG, but not significant for the individual components. In the unresectable population, the median overall survival was 13.5 compared to 25.0 months (p = 0.0008, HR 2.49, 95% CI 1.46-4.22) for positive vs. negative CISIG. IL-6 was independently prognostic with overall survival of 16.2 compared to 27.0 months (p = 0.004, HR 1.96, 95% CI 1.24-3.11) for high vs. low IL-6, but not the other components. Using a Cox regression model, we demonstrated that CISIG is an independent predictive marker of survival in patients with unresectable disease (HR 1.8, 95% CI 1.2, 2.8, p < 0.01).ConclusionIn two different cohorts, we demonstrated that CISIG is a strong prognostic factor of relapse-free and overall survival of patients with mCRC. Based on these data, analysis of circulating inflammatory signaling can be complimentary to traditional molecular testing.

Project description:BackgroundColorectal cancer (CRC) is the third most common malignancy in males and the second most common in females worldwide. Distant metastases have a strong negative impact on the prognosis of CRC patients. The most common site of CRC metastases is the liver. Both disease progression and metastasis have been related to the patient's peripheral blood monocyte count. We therefore performed a case-control study to assess the relationship between the preoperative peripheral blood monocyte count and colorectal liver metastases (CRLM).MethodsClinical data from 117 patients with colon cancer and 93 with rectal cancer who were admitted to the Chinese People's Liberation Army General Hospital (Beijing, China) between December 2003 and May 2015 were analysed retrospectively, with the permission of both the patients and the hospital.ResultsPreoperative peripheral blood monocyte counts, the T and N classifications of the primary tumour and its primary site differed significantly between the two groups (P < 0.001, P < 0.001, P = 0.002, P < 0.001), whereas there were no differences in the sex, age, degree of tumour differentiation or largest tumour diameter. Lymph node metastasis and a high preoperative peripheral blood monocyte count were independent risk factors for liver metastasis (OR: 2.178, 95%CI: 1.148~4.134, P = 0.017; OR: 12.422, 95%CI: 5.076~30.398, P < 0.001), although the risk was lower in patients with rectal versus colon cancer (OR: 0.078, 95%CI: 0.020~0.309, P < 0.001). Primary tumour site (P<0.001), degree of tumour differentiation (P = 0.009), T, N and M classifications, TNM staging and preoperative monocyte counts (P<0.001) were associated with the 5-year overall survival (OS) of CRC patients. A preoperative peripheral blood monocyte count > 0.505 × 109 cells/L, high T classification and liver metastasis were independent risk factors for 5-year OS (RR: 2.737, 95% CI: 1.573~ 4.764, P <0.001; RR: 2.687, 95%CI: 1.498~4.820, P = 0.001; RR: 4.928, 95%CI: 2.871~8.457, P < 0.001).ConclusionsThe demonstrated association between preoperative peripheral blood monocyte count and liver metastasis in patients with CRC recommends the former as a useful predictor of postoperative prognosis in CRC patients.

Dataset Information

Epithelial expression of FHL2 is negatively associated with metastasis-free and overall survival in colorectal cancer.

Background

Methods

Results

Conclusion

Publications

Epithelial expression of FHL2 is negatively associated with metastasis-free and overall survival in colorectal cancer.

Similar Datasets

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