Up-regulation of miR-9 expression as a poor prognostic biomarker in patients with non-small cell lung cancer

Purpose

Emerging evidences indicate that dysregulated microRNAs are implicated in cancer tumorigenesis and progression. MicroRNA-9 (miR-9) has various expression patterns in diverse human cancers. However, its clinical significance in human non-small cell lung cancer has not yet been elucidated. In the present study, we detected the expression of miR-9 in non-small cell lung cancer and adjacent noncancerous tissues and explored its relationships with clinicopathological characteristics and prognosis.

Methods

Expression levels of miR-9 in 116 pairs of non-small cell lung cancer and adjacent normal tissues were detected by real-time quantitative RT-PCR assay. To determine its prognostic value, overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan–Meier method. Univariate and multivariate analysis were performed using the Cox proportional hazard analysis.

Results

MiR-9 expression in non-small cell lung cancer tissues was significantly higher than that in adjacent normal tissues (p = 0.001), and its up-regulation was significantly correlated to advanced tumor–node–metastasis (TNM) stage (p < 0.001), tumor size (p = 0.013), and lymph node metastasis (p = 0.001). Furthermore, Kaplan–Meier analysis demonstrated that high miR-9 expression clearly predicted poorer PFS (p < 0.001) and OS (p < 0.001). In the multivariate analysis, increased miR-9 expression was an independent prognostic factor for both PFS (p = 0.002) and OS (p = 0.013).

Conclusions

MiR-9 was up-regulated in non-small cell lung cancer tissues and correlated with adverse clinical features and unfavorable survival, indicating that miR-9 might be involved in non-small lung cancer progression and could serve as a promising biomarker for further risk stratification in the treatment of this cancer.     

Decreased expression of microRNA-31 associates with aggressive tumor progression and poor prognosis in patients with bladder cancer

Purpose

MicroRNA-31 (miR-31) has different expression patterns in various human cancers. Especially in urothelial carcinoma of the bladder, it has been demonstrated to be decreased expression in the invasive tumors and homozygously deleted. However, its clinical significance in human bladder cancer has not yet been elucidated. Thus, the purpose of this study was to investigate the diagnostic and prognostic values of miR-31 in this disease.

Methods

Expression levels of miR-31 in 126 pairs of bladder cancer and adjacent normal tissues were detected by real-time quantitative RT-PCR assay. To determine its prognostic value, overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan–Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis.

Results

MiR-31 expression in bladder cancer tissues was significantly lower than those in adjacent normal tissues (mean expression level: 2.1 ± 0.9 vs. 3.8 ± 1.2, P < 0.001). When categorized into low vs. high expression, low miR-31 expression was negatively associated with the tumor stage (P = 0.02), the status of recurrence (P = 0.01), progression (P = 0.01), and death (P = 0.006) of patients with bladder cancer. Moreover, low miR-31 expression clearly predicted poorer PFS (P = 0.001) and OS (P < 0.001). In the multivariate analysis, low miR-31 expression was an independent prognostic factor for both PFS (P = 0.01) and OS (P = 0.008).

Conclusion

These findings show that miR-31 may contribute to the progression of bladder cancer and its downregulation may be independently associated with unfavorable PFS and OS, suggesting that miR-31 might be a promising marker for further risk stratification in the treatment of this cancer.     

Up-regulation of microRNA-183-3p is a potent prognostic marker for lung adenocarcinoma of female non-smokers

Background

Lung cancer in never smokers presents predominately as adenocarcinoma and in females. MicroRNA-183 (miR-183) has various expression patterns in types of human cancers. In the present study, we evaluated the expression of miR-183-3p in female lung adenocarcinoma and adjacent noncancerous tissues and explored its relationship with clinicopathological characteristics and prognosis.

Methods

In the present study, a hundred female nonsmoking patients who were newly diagnosed and histologically confirmed as lung adenocarcinoma at Tianjin Medical University Cancer Hospital were included. miR-183-3p expression of surgically removed NSCLC tissues and their corresponding normal lung tissues was measured by qRT-PCR assay. Associations of miR-183-3p expression with clinicopathological features were determined using the Student’s t test. Log-rank test, and Cox proportional hazards model were used for survival analysis.

Results

At first, miR-183-3p was up-regulated in lung cancer tissues when compared with the corresponding noncancerous lung tissues. Moreover, the expression of miR-183-3p in tumor tissue was found to be associated with lymph node metastasis (P = 0.043), clinical stage (P = 0.015), and EGFR mutation (P = 0.003). At last, high miR-183-3p expression was also associated with both poor overall survival and progression-free survival of women with lung adenocarcinoma (P = 0.005 and P = 0.010, respectively).

Conclusion

This study suggested that miR-183-3p expression might be involved in lung cancer pathogenesis and progression, and could be used as a potential prognostic biomarker of female lung adenocarcinoma.     

Increased serum level of epidermal growth factor receptor (EGFR) is associated with poor progression-free survival in patients with epithelial ovarian cancer

Purpose

Epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of multiple malignancies, and its expression also strongly affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of EGFR in epithelial ovarian cancer (EOC) patients.

Materials and methods

A total of 50 patients with a pathologically confirmed diagnosis of EOC were enrolled into this study. Serum EGFR levels were determined by the solid-phase sandwich ELISA method. Age and sex matched 20 healthy controls were included in the analysis.

Results

Median age of patients was 56.5 years old, range 22–83 years. Majority of the patients had advanced disease (FIGO stage III-IV) (90 %). No significant difference in baseline serum EGFR levels between EOC patients and controls (65.9 vs. 65.4 ng/mL, p = 0.86). Patients with normal CA 125 had higher serum EGFR level compared with the higher CA 125 level (p = 0.02). No other clinical variables including histology, stage of disease, and response to chemotherapy were found to be correlated with serum EGFR assay (p > 0.05). The patients with increased serum EGFR levels had poor progression-free survival than those with lower levels (median survival 4 vs. 12 months, respectively, p = 0.01). However, serum EGFR level was found no prognostic role for overall survival (p = 0.15).

Conclusion

Increased serum level of EGFR is associated with poor progression-free survival in EOC patients.     

Expression of Wilms’ tumor gene (WT1) is associated with survival in malignant pleural mesothelioma

Introduction

Calretinin and Wilms’ tumor gene (WT1) are mesothelial markers routinely used to confirm the diagnosis of malignant pleural mesothelioma (MPM). We investigated the prognostic value of calretinin and WT1 expression in predicting survival in a series of patients diagnosed with MPM in our institution.

Materials and methods

Fifty-two patients diagnosed of MPM were retrospectively reviewed. Calretinin and WT1 were stained for IHC analysis in formalin-fixed, paraffin-embedded sections and positivity was considered for tumors with >1 % of tumor cells stained. Survival data were calculated by the Kaplan–Meier method and Cox regression was used to evaluate the prognostic value of the variables.

Results

Calretinin IHC expression was positive in 83.7 % of patients and WT1 in 78.1 %. A significant association of calretinin and WT1 expression with epithelial histology was detected (p = 0.030 and p = 0.010). We found a significant increase in OS in patients with epithelial subtype, PS1 and neutrophil–lymphocyte ratio (NLR) ≤5 (p < 0.05). In the IHC markers analysis, we found a significant increase in OS for patients with WT1 positive expression (16.4 vs. 2.3 m, p = 0.013), but not differences for calretinin expression (16.6 vs. 5.0 months, p = 0.37). In the multivariate analysis, epithelial histology and WT1 remained as significant prognostic factors for survival (p = 0.004 and p = 0.010, respectively).

Conclusion

In our series of 52 MPM patients, epithelial histology, PS, NLR and WT1 expression are significant prognostic factors for survival. We concluded that WT1, but not calretinin, is a useful prognostic factor in MPM. The role of WT1 assessment is worth of prospective validation in future studies on MPM.     

Diagnostic and prognostic potential of serum miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429 in ovarian cancer patients

Background:

Owing to late diagnosis in advanced disease stages, prognosis of patients with epithelial ovarian cancer (EOC) is poor. The quantification of deregulated levels of microRNAs could facilitate earlier diagnosis and improve prognosis of EOC.

Methods:

Seven microRNAs (miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429) were quantified in the serum of 180 EOC patients and 66 healthy women by TaqMan PCR microRNA assays. Median follow-up time was 21 months. The effects of miR-7 and miR-429 on apoptosis, cell proliferation, migration and invasion were investigated in two (EOC) cell lines.

Results:

Serum levels of miR-25 (P=0.0001) and miR-93 (P=0.0001) were downregulated, whereas those of miR-7 (P=0.001) and miR-429 (P=0.0001) were upregulated in EOC patients compared with healthy women. The four microRNAs discriminated EOC patients from healthy women with a sensitivity of 93% and a specificity of 92%. The levels of miR-429 positively correlated with CA125 values (P=0.0001) and differed between FIGO I–II and III–IV stages (P=0.001). MiR-429 was an independent predictor of overall survival (P=0.011). Overexpressed miR-429 in SKOV3 cells led to suppression of cell migration (P=0.037) and invasion (P=0.011). Increased levels of miR-7 were associated with lymph node metastases (P=0.0001) and FIGO stages III–IV (P=0.0001). Overexpressed miR-7 in SKOV3 cells resulted in increased cell migration (P=0.001) and invasion (P=0.011). Additionally, the increased levels of miR-376a correlated with FIGO stages III–IV (P=0.02).

Conclusions:

Our data indicate the diagnostic potential of miR-7, miR-25, miR-93 and miR-429 in EOC and the prognostic potential of miR-429. This microRNA panel may be promising molecules to be targeted in the treatment of EOC.     

A prospective study of biomarker-guided chemotherapy in patients with non-small cell lung cancer

Purpose

To assess the therapeutic value of biomarker-guided chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).

Methods

Eighty-five NSCLC patients at stage IIIb or IV were divided into two groups based on the feasibility of biomarker analysis. Group A included patients with biomarker data (n = 41); Group B were patients without biomarker results (n = 44). Tumor samples obtained by fiberoptic bronchoscopy and computerized tomography-guided needle biopsy were analyzed by immunohistochemistry for intratumoral level of excision repair cross-complementing gene 1 (ERCC1), ribonucleotide reductase M1 (RRM1), and β-tubulin III. Chemotherapy regimens in Group A were determined according to the status of molecular signatures, whereas a standard gemcitabine plus cisplatin regimen was used for Group B. Tumor response, patient survival, and adverse effects were monitored for both groups.

Results

The overall response rate, defined as complete response plus partial response, was 56.1 % for Group A, significantly higher than that in Group B (31.8 %; P = 0.024). The median progression-free survival (PFS) time was 5.2 months for Group A, significantly longer than that of Group B (4.1 months; P = 0.026). The 1-year survival rate of Group A was 65.9 %, significantly higher than that of Group B (40.9 %; P = 0.021), whereas the median overall survival times were 13.5 versus 12.5 months for Groups A and B, respectively (P = 0.483). The adverse effects in the two groups were essentially the same.

Conclusions

Biomarker-tailored chemotherapy based on ERCC1, RRM1, and β-tubulin III expression showed significantly increased response rate, median PFS time, and 1-year survival rate in patients with NSCLC.     

Prognostic role of microRNA polymorphisms in patients with advanced esophageal squamous cell carcinoma receiving platinum-based chemotherapy

Purpose

MicroRNA (miRNA) polymorphisms contribute to cancer susceptibility and prognosis. The aim of this study was to evaluate the effects of miRNA polymorphisms on clinical outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) treated with platinum-based chemotherapy.

Methods

Five polymorphisms (miR-146a rs2910164, miR-196a2 rs11614913, miR-100 rs1834306, miR-125a rs12976445 and miR-26a1 rs7372209) were genotyped in 378 patients with advanced ESCC recruited at Zhongshan Hospital. The associations between genotypes and drug response, toxicity, and overall survival were analyzed.

Results

miR-146a rs2910164 was significantly associated with an increased risk of severe hematological toxicity [odds ratio = 0.374, 95 % confidence interval (CI) 0.171–0.819, P = 0.014]. The TT genotypes of both miR-196a2 rs11614913 and miR-125a rs12976445 were associated with worse survival [hazard ratio (HR) = 1.552, 95 % CI 1.112–2.165, P = 0.010; HR = 2.171, 95 % CI 1.173–4.017, P = 0.014, respectively]. Combined analysis revealed a 4.073-fold increased risk of death in patients carrying two unfavorable genotypes (P = 0.002).

Conclusions

Taken together, these findings indicate that miRNA polymorphisms may predict prognosis in advanced ESCC patients receiving platinum-based chemotherapy.     

A novel signaling role for miR-451 in esophageal tumor microenvironment and its contribution to tumor progression

Objective

We evaluated miR-451 expression in serum and tissue samples of esophageal squamous cell carcinoma (ESCC) patients. Then, we examined a secretory role of miR-451 in esophageal tumor microenvironment.

Methods

miR-451 expression was evaluated in 39 serum samples from esophageal SCC patients compared to 39 normal individuals as well as 26 pairs of fresh-frozen tumor and adjacent normal tissues from patients with ESCC, using qRT-PCR. In a co-culture system of human normal fibroblasts (HFSF-PI3) and esophageal cancer cell line (KYSE-30), we evaluated exosomal miR-451 secretion into the conditioned medium (CM) of both cell lines. Then, we analyzed the effect of primiR-451-transfected fibroblasts on the migration potency of their neighboring KYSE-30 cells.

Results

We detected miR-451 over-expression in serum samples of esophageal cancer patients compared to the normal group (P = 0.005). Interestingly, fresh-frozen tumor tissues from the same patients showed miR-451 down-regulation compared to their adjacent normal counterparts (P = 0.043). Co-culturing the KYSE-30 cell line with normal fibroblasts significantly induced miR-451 exosomal secretion into the CM. Moreover, co-culture of KYSE-30 cell line with miR-451-over-expressing fibroblasts significantly induced migration tendency in KYSE-30 cell line compared to the mock-transfected fibroblasts (P < 0.0001). In this system, MIF expression (a validated target of miR-451) in the KYSE-30 cell line was increased although this alteration was not statistically significant (fold change = 4.44).

Conclusions

Our data suggest that cancer-associated fibroblasts use exosomal miR-451 as a signaling molecule to provide a favorable niche for tumor cell migration and cancer progression. Our findings provide new insights into the stromal role of miR-451 in the esophageal tumor microenvironment as a communicatory molecule and suggest a signaling role for miR-451 in extracellular matrix cross-talks.

     

Clinical impact of systematic pelvic and para-aortic lymphadenectomy for pT1 and pT2 ovarian cancer: a retrospective survey by the Sankai Gynecology Study Group

Background

The therapeutic value of systematic lymphadenectomy for early-stage epithelial ovarian cancer (EOC) is controversial. This study evaluates the survival impact and adverse events of systematic pelvic and para-aortic lymphadenectomy in patients with pT1 and pT2 EOC.

Methods

A retrospective investigation was performed using data from patients with pT1 and pT2 EOC at multi-institutions belonging to the Sankai Gynecologic Study Group (SGSG). We selected patients who had undergone systematic pelvic and para-aortic lymphadenectomy (Group LA) (n = 284) and patients who had not undergone lymph node resection (Group no-LA) (n = 138). Outcomes for patients and peri-operative adverse events were compared between the two groups.

Results

The median operation time was significantly longer in Group LA (288 min) than in Group no-LA (128 min) (P < 0.0001). Total blood loss was significantly higher in Group LA, 43.7 % of patients receiving blood transfusions. There were no significant differences between the treatment groups for progression-free survival (PFS) or overall survival (OS). However, for patients with pT2, PFS was significantly longer in Group LA than in Group no-LA (P = 0.0150). Lymph node metastases were detected in 23 cases (8.1 %) and these patients had significantly shorter PFS than those without metastasis (P = 0.0409). The outcome for patients who underwent chemotherapy after surgery was significantly improved in the Group no-LA, but no improvement was observed in Group LA.

Conclusions

Systematic lymphadenectomy may improve outcomes only in pT2 EOC patients with acceptable peri-operative events. Furthermore, accurate surgical staging may avoid unnecessary adjuvant chemotherapy in selected early-stage cases.     

CHD1L is a novel independent prognostic factor for gastric cancer

Background

Chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) is involved in malignancies. However, the role of CHD1L in gastric cancer (GC) has not been elucidated. The aim of this study is to explore the clinical role of CHD1L in GC.

Methods

The gene and protein expression levels of CHD1L were detected by quantitative real-time PCR and Western blot analysis in fresh samples of GC and paired adjacent noncancerous tissue (n = 34). We evaluated the CHD1L expression by immunohistochemistry in a large number of GC patients (n = 616) and paired adjacent noncancerous tissues from December 1, 2004 to December 1, 2008. The correlations of CHD1L expression with clinicopathological features and clinical outcome were analyzed.

Results

The gene and protein expression levels of CHD1L were higher in fresh samples of GC than in paired adjacent noncancerous tissues as determined by quantitative real-time PCR and Western blot analysis. Immunohistochemical analysis showed that positive expression rates of CHD1L in GC and paired adjacent noncancerous tissues were 58.7 % (361/616) and 7.3 % (45/616), respectively. CHD1L positivity was significantly associated with clinical stage and distant metastasis. GC patients with positive CHD1L expression had shorter overall survival than those with negative CHD1L expression. Multivariate analysis showed that CHD1L was an independent prognostic marker for overall survival [Hazard Ratio (HR) = 5.952, 95 % confidence interval (CI) = 3.194–11.187, P = 0.0043].

Conclusion

These results indicated that CHD1L could serve as a prognostic marker for GC.     

The safety and efficacy of paclitaxel and carboplatin with or without bevacizumab for treating patients with advanced nonsquamous non-small cell lung cancer with interstitial lung disease

Purpose

Optimal chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) with interstitial lung disease (ILD) is established for paclitaxel and carboplatin, but is otherwise controversial. Therefore, we assessed the efficacy and safety of paclitaxel and carboplatin with or without bevacizumab for treating these patients.

Methods

We analyzed the outcomes of 21 patients with advanced nonsquamous NSCLC with ILD who received paclitaxel and carboplatin without (paclitaxel–carboplatin group; n = 11) or with bevacizumab (paclitaxel–carboplatin–bevacizumab group; n = 10) between April 2008 and October 2013.

Results

The median progression-free survival time of the paclitaxel–carboplatin–bevacizumab group was 5.3 months (95 % CI 0.4–11.6 months) compared with 4.4 months (95 % CI 0.9–6.3 months) for the paclitaxel–carboplatin group (p = 0.060). Their respective median overall survival times were 16.1 months (range 0.4–34.8 months) and 9.7 months (range 2.6–37.0 months) (p = 0.772) with corresponding overall response rates of 40 and 27 % (p = 0.659), respectively. One patient in the paclitaxel–carboplatin–bevacizumab group experienced chemotherapy-related exacerbation of ILD (0/11 vs. 1/10; p = 0.476).

Conclusions

The addition of bevacizumab to paclitaxel and carboplatin may provide an effective and safe treatment option for patients with advanced nonsquamous NSCLC with ILD.     

Predictive value of APE1, BRCA1, ERCC1 and TUBB3 expression in patients with advanced non-small cell lung cancer (NSCLC) receiving first-line platinum–paclitaxel chemotherapy

Purpose

Drug resistance is not only one of the major obstacles to treatment but also a poor prognosis in advanced non-small cell lung cancer (NSCLC) patients. The aim of this study was to evaluate the predictive value of APE1, BRCA1, ERCC1 and TUBB3 in advanced NSCLC patients who received platinum–paclitaxel treatment.

Methods

One hundred and thirty-six advanced NSCLC patients, who were treated with first-line platinum–paclitaxel chemotherapy, were enrolled in this study. The protein expression levels of APE1, BRCA1, ERCC1 and TUBB3 were assessed by immunohistochemistry and analyzed for the association with response to chemotherapy and progression-free survival (PFS) and overall survival (OS).

Results

Patients with negative expression of APE1, ERCC1 or TUBB3 benefited from platinum plus paclitaxel regimen chemotherapy. ERCC1-negative patients had better PFS (P = 0.016) and OS (P = 0.030) compared with positive patients. Similarly, the APE1-negative patients showed better PFS (P = 0.004) and longer OS though statistically insignificant. Multivariate analysis showed that APE1 and ERCC1 were independent predictor for PFS (HR 2.07; P = 0.004 and HR 1.66; P = 0.016) and OS (HR 1.99; P = 0.008 and HR 1.64; P = 0.040). Moreover, patients with both APE1- and ERCC1-negative or both APE1- and TUBB3-negative tumors had significantly higher response rate, longer median PFS and OS following treatment with platinum and paclitaxel (P < 0.05).

Conclusion

The data indicate that APE1, ERCC1 and TUBB3 could be a useful biomarker to predict clinical outcome in patients with advanced NSCLC receiving first-line platinum–paclitaxel chemotherapy.     

Snail1 correlates with patient outcomes in E-cadherin-preserved gastroesophageal junction adenocarcinoma

Purpose

The poor prognosis of gastroesophageal junction (GEJ) adenocarcinoma is largely associated with metastasis. We here report the first study to investigate the expression of epithelial-mesenchymal transition (EMT) markers Snail1 and E-cadherin in GEJ adenocarcinoma.

Methods

Snail1 and E-cadherin were detected by immunohistochemistry in a cohort of 128 patients with surgically resected GEJ adenocarcinoma. We assessed the pathologic and prognostic relevance in all patients and within clinically different preserved E-cadherin and reduced E-cadherin-expressing sub-groups.

Results

Immunoreactivity for Snail1 and E-cadherin was positive in 68 and 43 % of tumors, respectively. Snail1-positive tumors had more frequent lymph node metastasis and advanced tumor stage. E-cadherin expression was highly associated with histological differentiation, tumor size, advanced stage, presence of lymph node metastasis and distant metastasis. Patients with positive E-cadherin expression or negative Snail1 expression had significantly favorable overall survival rate. In E-cadherin-preserved tumors, the expression of Snail1 was related to lymph node metastasis, advanced stage and poor patient outcome. However, Snail1 expression had no statistically significant relationship with clinicopathologic parameters or prognosis in the reduced E-cadherin-expressing sub-group. Multivariate survival analysis identified that tumor stage [hazard ratio (HR) 2.440; 95 % confidence interval (CI) 1.216–4.896; P = 0.012], lymph node metastasis (HR 2.404; 95 % CI 1.188–4.867; P = 0.015) and gender (HR 3.244; 95 % CI 1.568–6.714; P = 0.002) were independent prognostic markers for overall survival.

Conclusions

Snail1 may act more critically in E-cadherin-positive tumors. Evaluation of Snail1 and E-cadherin in GEJ adenocarcinoma may help in assessing malignant properties and stratifying patients.     

High Sam68 expression predicts poor prognosis in non-small cell lung cancer

Background

The nuclear protein Sam68 has been implicated in the oncogenesis and tumor growth. The aim of this study was to explore the clinical value of Sam68 in patients with non-small cell lung cancer (NSCLC).

Methods

We examined Sam68 expression in 50 NSCLC tissues and matched adjacent noncancerous tissues by quantitative RT-PCR (qRT-PCR) and Western blotting. Furthermore, the Sam68 protein expression was analyzed by immunohistochemistry in 208 NSCLC samples. Kaplan–Meier method and multivariate Cox regression model were used to evaluate the prognostic value of nuclear Sam68 expression in NSCLC for disease survival.

Results

The expression of Sam68 was significantly elevated in NSCLC tissues as compared with adjacent non-cancerous tissues (P < 0.01). The high expression of Sam68 in NSCLC was significantly correlated with lymph node metastasis and tumor TNM stage. Kaplan–Meier survival analysis revealed that high expression of Sam68 correlated with poor prognosis of NSCLC patients (P < 0.01). Multivariate analysis showed that Sam68 expression was an independent prognostic marker for overall survival of NSCLC patients (HR 2.73, 95 % CI 1.549–4.315, P = 0.002).

Conclusion

Our results suggest that high Sam68 expression predicts poor prognosis of NSCLC patients, and Sam68 may be potentially a prognostic biomarker for NSCLC.     

A high serum level of M65 is associated with tumour aggressiveness and an unfavourable prognosis for epithelial ovarian cancer

Purpose

This study was conducted to determine the clinical significance of serum M30 and M65 in epithelial ovarian cancer (EOC).

Methods

A total of 56 patients with EOC and 56 healthy women were included in the study. All of the patients received platinum-based chemotherapy. Pretreatment levels of M30 and M65 were measured using the quantitative ELISA method.

Results

The median M30 and M65 serum levels were significantly elevated in the EOC patients compared with the healthy controls (96.7 vs. 69.5, p = 0.028 and 436.4 versus 166.3, p < 0.001, respectively). The cut-off value of 423.4 U/L for M65 determined with ROC analysis, predicted progression with 75.1 % sensitivity and 65.6 % specificity (AUC = 0.708, p = 0.008). Patients with higher M65 levels had shorter progression-free survival (PFS) (p = 0.021). Both M30 and M65 serum levels were significantly higher for serous-type histology (p = 0.001 and p < 0.001, respectively). Increased M65 serum levels were associated with advanced disease (p = 0.005) and higher grade (p = 0.005). Moreover, M65 levels were higher for chemotherapy-resistant patients (p = 0.04). Multivariate analysis revealed that an elevated serum M65 level was the only significant independent prognostic factor (p = 0.039, HR 3.792).

Conclusions

These results indicated that serum M30 and M65 levels were significantly elevated in patients with EOC compared with healthy women. Particularly, high serum M65 levels were associated with poor prognosis and resistance to platinum-based chemotherapy.     

Expression of a novel endothelial marker,C-type lectin 14A,in epithelial ovarian cancer and its prognostic significance

Objective

The purpose of this study was to evaluate microvessel density (MVD) as assessed by C-type lectin 14A (CLEC14A), which is a new marker for endothelial cells, and compare its expression to CD31 and CD105 in epithelial ovarian cancer (EOC).

Methods

MVD was evaluated in tumors (n = 50) from patients with EOC who underwent primary surgery and in patients with EOC who received preoperative chemotherapy (n = 49) using immunohistochemistry with antibodies to CLEC14A, CD31 and CD105. The median duration of follow-up was 24.5 months (range 1?101 months). The effect of prognostic factors on event-free survival (EFS) and overall survival (OS) was assessed using the Cox regression model.

Results

The amount of residual disease was found to be an independent prognostic factor in multivariate analysis with respect to EFS (P = 0.009) and OS (P < 0.001). The mean MVD of CLEC14A (MVD = 6), in tumors from patients who underwent primary surgery, was significantly lower than that of CD31 (MVD = 25, P < 0.0001) and CD105 (MVD = 11, P = 0.018). However, there was no significant correlation between MVD as detected by these markers and clinical outcome. There was no expression of CLEC14A in tumors from patients who received preoperative chemotherapy and the MVD of CD31 and CD105 was significantly reduced (P = 0.001 and 0.006, respectively) in this set of patients.

Conclusion

This study demonstrates MVD as detected by CLEC14A in EOC. Treatment with chemotherapy reduces tumor blood vessels significantly. We suggest that CLEC14A may be a more specific endothelial marker to assess tumor angiogenesis.