Matrix metalloproteinase 2 polymorphisms and expression in lung cancer: a meta-analysis

A number of studies have investigated the role of matrix metalloproteinase 2 (MMP2) polymorphisms and expression in lung cancer, but have yielded inconsistent and inconclusive results. To derive a more precise estimate of the prognostic role of MMP2 expression and the susceptibility role of MMP2 polymorphisms in lung cancer, we reviewed published studies and carried out a meta-analysis. Eligible articles were identified in electronic databases. Case?Ccontrol studies assessing the associations between MMP2 polymorphisms and lung cancer risk or cohort studies assessing the prognostic role of MMP2 expression in patients with lung cancer were included. Pooled odds ratio (OR) or hazard ratio (HR) with 95?% confidence interval (95?% CI) was used to assess the role of MMP2 polymorphisms and expression in lung cancer, respectively. Seven case?Ccontrol studies (a total of 3,190 lung cancer cases and 3,013 controls) and 18 cohort studies (2,095 lung cancer patients) were eligible. Meta-analysis of seven case?Ccontrol studies suggested that individuals with TT genotype of both MMP2 C735T and C1306T polymorphisms had obviously decreased risk of lung cancer compared with those with CC genotype (for MMP2 C735T, fixed effects OR?=?0.69, 95?% CI 0.49?C0.97, P?=?0.032; for MMP2 C1306T, fixed effects OR?=?0.54, 95?% CI 0.33?C0.86, P?=?0.010). Meta-analysis of 18 cohort studies suggested that patients with high MMP-2 expression had poorer overall survival (fixed effects HR?=?1.82, 95?% CI 1.56?C2.13, P?<?0.001). Subgroup by study design, ethnicity and testing methods all further identified the prognostic value of MMP2 expression in lung cancer. In conclusion, MMP2 C735T and C1306T polymorphisms are both associated with lung cancer risk, and patients with high MMP2 expression levels have poorer overall survival compared with those with low MMP2 expression levels.     

基质金属蛋白酶-9与结直肠癌

基质金属蛋白酶（MMP）能够降解细胞外基质,对肿瘤生长、侵袭和扩散至关重要。作为MMP 家族中相对分子质量最大的,MMP-9参与结直肠癌的生成和进展。研究显示 MMP-9可用于结直肠癌患者的早期诊断,组织和血浆中 MMP-9表达水平与结直肠癌患者术后预后呈负相关。另外,针对MMP-9在结直肠癌组织中表达增加这一特点可设计相关的靶向治疗药物。     

Thymidylate synthase expression and prognosis in colorectal cancer: a systematic review and meta-analysis.

PURPOSE: A number of studies have investigated the relationship between thymidylate synthase (TS) expression and survival in colorectal cancer (CRC) patients. Although most have reported poorer overall and progression-free survival with high TS expression, estimates of the hazard ratio (HR) between studies differ wildly. To derive a more precise estimate of the prognostic significance of TS expression, we have reviewed published studies and carried out a meta-analysis. MATERIALS AND METHODS: Twenty studies stratifying overall survival and/or progression-free survival in CRC patients by TS expression status were eligible for analysis. The principal outcome measure was the HR. Data from these studies were pooled using standard meta-analysis techniques. RESULTS: Thirteen studies investigated outcome in a total of 887 cases with advanced CRC, and seven studies investigated outcome in a total of 2,610 patients with localized CRC. A number of methods were used both to assess TS expression and to assign TS status. Sample sizes varied greatly, small sample sizes being a feature of the advanced disease studies. The combined HR estimate for overall survival (OS) was 1.74 (95% CI, 1.34 to 2.26) and 1.35 (95% CI, 1.07 to 1.80) in the advanced and adjuvant settings, respectively, but there was evidence of heterogeneity and possible publication bias. CONCLUSION: Tumors expressing high levels of TS appeared to have a poorer OS compared with tumors expressing low levels. Additional studies with consistent methodology are needed to define the precise prognostic value of TS.     

Matrix metalloproteinase 2 and 9 in esophageal cancer

To search for the biochemical properties of esophageal carcinoma relevant to its aggressive behavior, we studied metalloproteinases released from surgical specimens of the carcinoma. In an assay with [H-3]-labeled gelatin, esophageal carcinoma tissues showed gelatinolytic activities clearly higher than those of paired normal mucosae. EDTA and TIMP-1 could strongly suppress these activities, suggesting that the activities belong to metalloproteinases. In addition, levels of TIMP-1 expression did not show good correlation with these activities, suggesting that tumor-specific elevation of gelatinolytic activity depended on metalloproteinase per se rather than the suppression of TIMP-1-secretion. By zymographic analysis, two gelatinase bands of 82- and 62-kDa were found specifically in carcinoma tissues, in addition to the other 6 bands detected both in normal and carcinoma tissues. Immunoprecipitation and immunoblotting of gelatinases with anti-MMP-9 or anti-MMP-2 monoclonal antibody, and treatment of the enzymes with APMA showed that these 82- and 62-kDa gelatinases were cleaved products of MMP-9 and MMP-2, respectively. These results imply that enhanced secretion and proteolytic activation of MMP-2 and MMP-9 take place specifically in the esophageal carcinoma tissues. Moreover, the levels of gelatinolytic activity expressed good correlation with the organ metastasis rate of the carcinoma, suggesting that MMPs play an important role in tumor metastasis.     

Matrix metalloproteinase 2 expression and survival of patients with osteosarcoma: a meta-analysis

A number of studies investigated the impact of matrix metalloproteinase 2 (MMP2) expression on the survival of patients with osteosarcoma, but no consistent results were reported. To derive a more precise estimate of the prognostic role of MMP2 expression in patients with osteosarcoma, we systematically reviewed the published studies and carried out a meta-analysis. Cohort studies assessing the prognostic role of MMP2 expression in patients with osteosarcoma were included. Pooled risk ratio (RR) with 95 % confidence intervals (95%CI) was used to assess the prognostic role of MMP2 expression. Five cohort studies were eligible in the meta-analysis. Overall, high MMP2 expression was associated with increased risk of mortality in patients with osteosarcoma during the follow-up (fixed effects RR?=?2.14, 95%CI 1.66–2.75, P?<?0.001). Sensitivity analysis suggested that the pooled RR was stable and omitting a single study did not change the significance of the pooled RR. There was some possibility of publication bias risk in the meta-analysis. In conclusion, the meta-analysis suggests that osteosarcoma patients with high MMP2 expression have poorer prognosis compared with those with low MMP2 expression.     

Matrix metalloproteinase 9 in mucosally invasive gastric cancer

Background. Matrix metalloproteinase 9 (MMP-9) facilitates tumor invasion and metastasis via basement membrane degradation. Control of MMP-9 production by cancer-stromal cell interactions in these processes has been observed. Methods. We measured plasma MMP-9 concentrations, using a one-step sandwich enzyme immunoassay, and also immunohistochemically localized MMP-9 in patients with small gastric cancers limited to the mucosa. The cancers were classified as intraepithelial tumor (Tis) and T1 disease according to the tumor-node-metastasis (TNM) classification of the International Union Against Cancer. Results. Patients with T1 disease had a higher positivity rate for and mean value of MMP-9 than patients with Tis disease. In T1 tumors, MMP-9 expression determined immunohistochemically, was greater in cells in cancer stroma than in cells in noncancerous stroma, a situation found in only a few Tis tumors. Conclusions. These results suggest that MMP-9 is related to the initial step of gastric cancer invasion. Received for publication on Jun. 8, 1998; accepted on Oct. 20, 1998     

E-cadherin expression and prognosis of oral cancer: a meta-analysis

This study aims to evaluate the association of E-cadherin expression with the prognosis of oral squamous cell carcinoma (OSCC). Literature retrieval, selection and assessment, data extraction, and meta-analyses were performed according to the Revman 5.0 guidelines. In the meta-analysis, we utilized either fixed effects or random effects model to pool the HR according to the test of heterogeneity. A total of nine eligible studies included 973 OSCC patients were analyzed. Of the patients, 76.3 % had low expression of E-cadherin according to the cutoff value defined by the authors. The pooled hazard ratio (HR) of low expression of E-cadherin for overall survival (OS) was 0.65 (95 % CI 0.52 to 0.80, P?<?0.001); in Asian population, the HR for overall survival of the patients with reduced expression of E-cadherin was 0.84 (95 % CI 0.75 to 0.95, P?=?0.006), and in non-Asian population, the HR for overall survival of the patients with reduced expression of E-cadherin was 0.54 (95 % CI 0.41 to 0.69, P?<?0.001). Patients with reduced expression of E-cadherin appear to have a poorer OS compared with those with normal or higher expression of E-cadherin.     

Matrix metalloproteinase/tissue inhibitors of matrix metalloproteinase phenotype identifies poor prognosis colorectal cancers.

PURPOSE: The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes involved in tumor invasion; several individual members of which have been implicated in tumor prognosis. These enzymes and their physiologic inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs), act in a coordinated manner to form an integrated system. Therefore, to understand their role in tumor invasion, it is necessary to evaluate them collectively. EXPERIMENTAL DESIGN: In this study all of the major members of the matrix metalloproteinase (MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, MT1-MMP and MT2-MMP)/tissue inhibitor of matrix metalloproteinase (TIMP-1, TIMP-2, and TIMP-3) system have been investigated by immunohistochemistry in a series (n = 90) of stage III (Dukes' C) colorectal cancers. An immunohistochemical score based on the intensity of immunoreactivity and proportion of immunoreactive cells was established for each MMP and TIMP. RESULTS: The MMP/TIMP profile defined by hierarchical cluster analysis of the immunohistochemical score identifies a distinct group of colorectal cancers with poor prognosis (log-rank test, 12.22, P = 0.0005). The median survival time of patients in this survival group was 18 months compared with a median survival of 49 months in the "good" survival group. Multivariate analysis showed that this profile was independently the most significant prognostic factor (P = 0.001). CONCLUSIONS: This study has identified that the MMP/TIMP profile is an independent indicator of poor prognosis in colorectal cancer.     

Matrix metalloproteinase-9 as a prognostic factor in gastric cancer: a meta-analysis

Background: Matrix metalloproteinase-9 (MMP-9) is associated with disruption of basement membranesof blood vessels and promotion of metastasis through the lymphatics. However, its prognostic value for survivalin patients with gastric cancer remains controversial. Method: We therefore conducted a meta-analysis of thepublished literature in order to clarify the impact of MMP-9. Clinical studies were selected for further analysisif they provided an independent assessment of MMP-9 in gastric cancer and reported analysis of survival dataaccording to MMP-9 expression. Results: A total of 11 studies, covering 1700 patients, were included for metaanalysis.A summary hazard ratio (HR) of all studies and sub-group hazard ratios were calculated. The combinedHR suggested that a positive MMP-9 expression had an impact on overall survival: 1.25 (95% confidence interval1.11-1.40) in all eligible studies; 1.13 (1.06-1.20) in 8 studies detecting MMP-9 by immunohistochemistry; 1.36(1.12-1.65) in 7 studies from Asia. Only one study for DFS showed a significant impact on disease free survival(HR 1.73, 95%CI 1.27-2.34). Conclusions: Our findings suggested that MMP-9 protein expression might be afactor for a poor prognosis in patients with gastric cancer. However, the association was rather weak, so that moreprospective studies should further explore the prognostic impact of MMP-9 mRNA and correlations betweenMMP-9 and clinicopathological characteristics.     

Tumour-infiltrating inflammation and prognosis in colorectal cancer: systematic review and meta-analysis

Background:

The role of tumour-infiltrating inflammation in the prognosis of patients with colorectal cancer (CRC) has not been fully evaluated. The primary objective of our meta-analysis was to determine the impact of tumour-infiltrating inflammation on survival outcomes.

Methods:

Ovid MEDLINE and EMBASE were searched to identify studies reporting the prognostic significance of tumour-infiltrating inflammation for patients with CRC. The primary outcome measures were overall survival (OS), cancer-specific survival (CS) and disease-free survival (DFS).

Results:

A total of 30 studies involving 2988 patients were identified. Studies were subdivided into those considering the associations between CRC survival and generalised tumour inflammatory infiltrate (n=12) and T lymphocyte subsets (n=18). Pooled analyses revealed that high generalised tumour inflammatory infiltrate was associated with good OS (HR, 0.59; 95% CI, 0.48–0.72), CS (HR, 0.40; 95% CI, 0.27–0.61) and DFS (HR, 0.72; 95% CI, 0.57–0.91). Stratification by location and T lymphocyte subset indicated that in the tumour centre, CD3⁺, CD8⁺ and FoxP3⁺ infiltrates were not statistically significant prognostic markers for OS or CS. In the tumour stroma, high CD8⁺, but not CD3⁺ or FoxP3⁺ cell infiltrates indicated increased OS. Furthermore, high CD3⁺ cell infiltrate was detected at the invasive tumour margin in patients with good OS and DFS; and high CCR7⁺ infiltrate was also indicated increased OS.

Conclusion:

Overall, high generalised tumour inflammatory infiltrate could be a good prognostic marker for CRC. However, significant heterogeneity and an insufficient number of studies underscore the need for further prospective studies on subsets of T lymphocytes to increase the robustness of the analyses.     

Chemotherapy-induced neutropenia and the prognosis of colorectal cancer: a meta-analysis of cohort studies

Introduction: Recently, there has been a controversial discussion about the prognostic value of chemotherapy-induced neutropenia (CIN) in colorectal cancer patients. Thus, a meta-analysis was conducted to determine the relationship between CIN and the prognosis of colorectal cancer patients.

Methods: We searched the PubMed, EMBASE, and Cochrane library databases to identify studies evaluating the association between CIN and colorectal cancer prognosis. Pooled random/fixed effect models were used to calculate pooled hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the association.

Results: Eight studies were selected for the meta-analysis, for a total of 2,745 patients. There was significant improved survival among colorectal cancer patients with CIN (HR = 0.62, 95% CI = 0.47–0.76). However, significant heterogeneity was found (p = 0.000, Ι² = 75.0%). Through subgroup analysis, we could greatly eliminate the heterogeneity and found that neutropenia was associated with better survival in stage IV colorectal cancer patients, no matter the HR calculated by overall survival (OS) or progression-free survival (PFS). Meanwhile, the prognostic value of neutropenia in stage II/III colorectal cancer can be found when the HR is calculated by disease-free survival (DFS). Additionally, we observed significant differences after stratification according to various tumor stages, endpoints, and the use of G-CSF.

Conclusions: Our results which, based on a cohort study, indicate that CIN is associated with improved survival in patients with colorectal cancer. However, further randomized controlled trials are warranted.     

乳腺癌中MTA1、MMP-9 mRNA表达与临床病理研究

目的:探讨MTA1、MMP-9 mRNA表达量与乳腺癌淋巴转移的关系及临床意义,初步探讨MTA1、MMP-9 mRNA之间的关系.方法:采用免疫组化法对45例侵润性乳腺导管癌中MTA1表达进行检测,原位杂交法对MMP-9 mRNA表达进行检测.结果:乳腺癌中MTA1、MMP-9 mRNA(肿瘤细胞)、MMP-9 mRNA(间质细胞)阳性表达率为71%、49%、58%.MTA1与淋巴结转移相关,与年龄、肿瘤大小、ER、PR、c-erbB-2无相关性;MTA1蛋白定位变化与乳腺癌淋巴结转移相关(P<0.05); MMP-9 mRNA(肿瘤细胞)与临床病理特征均无相关性;MMP-9 mRNA(间质细胞)与淋巴结转移正相关(P<0.05),与PR呈负相关(P<0.05); MTA1阴性时肿瘤细胞内MMP-9 mRNA表达率为38%,MTA1阳性时MMP-9 mRNA表达率为50%,无显著性差异.结论:MTA1高表达促进乳腺癌细胞的淋巴结转移,MTA1蛋白定位变化与乳腺癌淋巴结转移相关;MTA1的过度表达可能是导致肿瘤细胞内MMP-9 mRNA表达下降的因素.     

Distinct pattern of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 mRNA expression in human colorectal cancer and liver metastases.

The matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are perceived as essential for tumour invasion and metastasis. In the present study, we compare the topographical pattern of MMP-9 and TIMP-1 expression in colorectal cancer and liver metastasis by in situ hybridisation. TIMP-1 mRNA was detected in all 26 colorectal cancers examined, while only 18 out of 26 (69.2%) were positive for MMP-9. Both MMP-9 and TIMP-1 mRNA were observed in all ten liver metastases but were absent in three adenomas and in all normal colonic mucosa and liver. There was no association between MMP-9 or TIMP-1 mRNA expression and degree of differentiation or size of Tumours. MMP-9 and TIMP-1 mRNA were similarly observed in the peritumour stroma cells rather than in tumour cells themselves. MMP-9 mRNA positive cells were round and identified as macrophages by immunostaining with an anti-macrophage antibody (KP1), while TIMP-1, mRNA was detected in spindle-shaped stromal cells. In liver metastases, MMP-9 localised within peritumour stroma or at the interface between the tumour stroma and normal liver, whereas TIMP-1 mRNA was located throughout the malignant tumour stroma. Our data demonstrate a distinct pattern of MMP-9 and TIMP-1 mRNA expression in colorectal cancer and liver metastases suggesting distinct cellular origins as well as separate patterns of regulation.     

Matrix metalloproteinase expression and outcome in patients with breast cancer: analysis of a published database

Traditionally, matrix metalloproteinases (MMPs) have been implicated in cancer invasion and metastasis. Because of their role in these processes, several MMPs have been investigated for potential prognostic value as well as targets for antimetastatic therapy. In this investigation, we used a publically available database to relate messenger RNA expression levels for 17 different MMPs to tumor characteristics and outcome in patients with breast cancer. Of the MMPs investigated, only MMP-1 was significantly increased in tumors >2 cm in size compared with those ≤2 cm while MMP-1, -9, -12 and -15 were significantly elevated in high-grade compared with low-grade tumors. Only MMP-10 was higher in lymph node-positive compared with lymph node-negative cancers. Using univariate analysis, high expressions of MMP-1, -9, -12, -14 and -15 were associated with poor overall survival. Of these five, only MMP-14 predicted outcome independent of tumor size, tumor grade and lymph node status. None of the MMPs investigated were associated with good outcome. We conclude that only a minority of MMPs, i.e. MMP-1, -9, -12, -14 and -15, are associated with adverse outcome in patients with breast cancer. These MMPs are likely to be involved in mediating breast cancer progression and may thus be good targets for designing specific MMP inhibitors for the treatment of breast cancer.     

XRCC1 and GSTP1 polymorphisms and prognosis of oxaliplatin-based chemotherapy in colorectal cancer: a meta-analysis

Purpose

Genetic variations are related to individual differences of DNA repair ability and drug metabolism, which can greatly influence prognosis of antineoplastic agents, such as oxaliplatin. The aim was to explore the influences of X-ray repair cross-complementing 1(XRCC1) and Glutathione S-transferase P1 (GSTP1) genetic variants on prognosis of oxaliplatin-based chemotherapy in colorectal cancer patients.

Methods

We performed a meta-analysis including 13 original studies with a total number of 1,234 patients in advanced or metastatic colorectal cancer. Tumor responses [complete response, partial response, stable disease (SD) and progressive disease (PD)] and progression-free survival were estimated.

Results

Our results showed that XRCC1 Arg399Gln polymorphism was significantly associated with tumor chemotherapy when SD or PD was considered as non-response [risk ratio (RR) = 1.29; 95 % confidence intervals (CI): 1.05–1.60; P = 0.02]. No significant association was found between GSTP1 Ile105 Val polymorphism and tumor response (RR = 0.63; 95 % CI: 0.35–1.14; P = 0.13). In addition, our results also showed that there was no significant association between XRCC1 codon 399 Arg/Gln or Gln/Gln genotypes and hazard ratio for progression-free survival (Hazards ratio = 1.04 and 1.92; 95 % CI: 0.75–1.43 and 0.62–1.37; P = 0.826 and 0.677, respectively).

Conclusion

In our meta-analysis, XRCC1 Arg399Gln polymorphism may be a valuable genetic marker for oxaliplatin-based chemotherapy in colorectal cancer, and the results still need further confirmation.     

Matrix metalloproteinase 9 expression in primary human prostatic adenocarcinoma and benign prostatic hyperplasia.

Matrix metalloproteinase (MMP) expression was investigated in patients with prostatic adenocarcinoma and benign prostatic hyperplasia (BPH). Forty-one men were studied: 26 had histologically proven prostate cancer, with 14 (54%) showing metastatic disease; 15 patients had BPH. Prostatic tissue was obtained from transurethral resection and needle core biopsies; gelatinolytic activity was determined by zymography. Seven gelatinolytic bands were detected, with molecular weights ranging from > 100 kilodalton (kDa) to 29 kDa. Nine of 14 patients (64%) with skeletal metastases had 92 kDa activity, present in only two of 12 patients (17%) with a negative bone scan, and absent in BPH. The 92 kDa gelatinolytic activity was expressed in 73% of aneuploid tumours compared with 20% of diploid tumours. A 97 kDa gelatinase was expressed in 80% of BPH samples and 23% of carcinoma patients. Enzyme bands of 72, 66 and 45 kDa were equally expressed in malignant tissue, irrespective of metastatic status, but were expressed in fewer BPH patients. The 97, 92, 66 and 45 kDa enzymes were identified as being pro-MMP-9 sequences by Western blotting, using a specific antibody directed against the pro sequence of the mature protein. MMP activity appeared to be increased in malignant prostatic tissue compared with BPH. Pro-MMP-9, in its 92 kDa form, was shown to be exclusively expressed by malignant prostatic tissue, and in particular by tumours that exhibited the aggressive and metastatic phenotype.     

Serum matrix metalloproteinase 7 levels identifies poor prognosis advanced colorectal cancer patients

Metalloproteinase 7 (MMP-7) plays an important role in tumor growth, invasion and dissemination, and is secreted to the media. Because of the close implication of MMP-7 in cancer biology, we sought to define the prognostic significance of serum levels of MMP-7 in metastatic colorectal cancer (CRC) and explore its possible impact in the daily clinical practice. MMP-7 expression was determined by enzyme-linked immunoabsorbent assay. We assessed serum MMP-7 levels in 87 healthy controls, 96 patients with nonmetastatic CRC and 120 patients with advanced CRC. Clinical information was gathered from patient files. Cox proportional hazards model was used to assess survival. MMP-7 and the variables associated with prognosis were entered and a backward elimination method was employed to adjust the model. Inclusion criteria was p /= 0.10. Advanced CRC patients have a significant higher mean serum MMP-7 levels (13.4 ng/ml) than those in nonmetastatic CRC (5.5 ng/ml; p < 0.001) and healthy controls (4.2 ng/ml; p < 0.001). In metastatic patients, after adjusting for other prognostic variables, MMP-7 (entered as a continuous variable) is associated with decreased survival (HR 1.016, IC 95% 1.002-1.031). Serum MMP-7 levels are significantly elevated in patients with advanced CRC. In conclusion, MMP-7 is an independent prognostic factor for survival in advanced CRC. In our sample, the risk of death associated to MMP-7 increase is much higher than the risk of death associated to lactate dehydrogenase elevation.     

Cyclin e expression and prognosis in breast cancer patients: a meta-analysis of published studies

In vitro studies showed that cyclin E can accelerate the cell cycle by shorten the G1/S phase transition. Therefore, varieties of studies have investigated the relationship between cyclin E and survival in breast cancer patients. However, the results differed widely between studies. We reviewed the published studies and performed a meta-analysis, which including 12 independent studies and 2,534 patients. The combined HR estimate for relapse-free survival (RFS) was 2.32 (95% CI, 1.25-4.30) and 1.72 (95% CI, 0.95-3.10) in univariate and multivariate analysis, respectively. In addition, the combined HR estimate for overall survival (OS) and breast cancer specific survival (BCSS) was 2.98 (95% CI, 1.85-4.78) and 2.86 (95% CI, 1.85-4.41) in univariate and multivariate analysis, respectively. In conclusion, the high level of cyclin E appears to be an independent prognostic factor to OS/BCSS of breast cancer patients but not to RFS.     

基质金属蛋白酶-9对结直肠癌侵袭转移的影响

 基质金属蛋白酶-9（MMP-9）是结直肠癌发生发展的重要促进基因,能够诱导结直肠癌细胞增殖、血管新生和肿瘤浸润,导致结直肠癌的侵袭转移。MMP-9对结直肠癌侵袭转移的影响既可独自完成又可与其他基因联合完成,是结直肠癌晚期转移的重要蛋白酶。     

Abnormal expression of TRIB3 in colorectal cancer: a novel marker for prognosis

Background:

TRIB3 is a human homologue of Drosophila tribbles. Previous studies have shown that TRIB3 controls the cell growth through ubiquitination-dependent degradation of other proteins, whereas its significance in the prognosis of colorectal cancer (CRC) is not yet fully understood.

Materials:

This study comprised 202 patients who underwent surgery for CRC, as well as 22 cell lines derived from human gastrointestinal cancer. The correlation of gene expression with clinical parameters in patients was assessed. The biological significance was evaluated by knockdown experiments in seven colorectal cancer cell lines.

Results:

A total of 20 cancer cell lines (90.9%) expressed the TRIB3 gene. The assessment in surgical specimens indicated that the gene expression was significantly higher in the cancerous region than in the marginal non-cancerous region. Patients with high TRIB3 expression were statistically susceptible to a recurrence of the disease, and showed poorer overall survival than those with low expression. The assessment of TRIB3 knockdown in five cell lines showed that small interfering RNA (siRNA) inhibition resulted in a statistically significant reduction in cell growth.

Conclusion:

These data strongly suggest the usefulness of TRIB3 as a marker for predicting the prognosis of CRC patients, showing a basis for the development of effective treatments for CRC.