Deyuan Fu

Expression and Prognostic Value of miR-486-5p in Patients with Gastric Adenocarcinoma

MicroRNA (miR)-486-5p expression is often reduced in human cancers. However, its expression in gastric carcinoma and its relation to clinicopathological features and prognosis are unclear. Tissue microarrays were constructed from 84 patients with gastric adenocarcinoma (GC) who were undergoing radical resection. miR-486-5p expression was detected by miRNA-locked nucleic acid in situ hybridization, and its correlations with clinicopathological features and overall survival were analyzed. Bioinformatic studies predict that fibroblast growth factor 9 (FGF9) is a potential target gene of miR-486-5p. miR-486-5p was mainly located in the cytoplasm of GC cells and neighboring normal tissues. Compared with paracancerous normal tissue, miR-486-5p expression was decreased in 63.1% (53/84) of the GC samples, increased in 32.1% (27/84) and unchanged in 4.8% (4/84). FGF9 expression was decreased in 69.0% (58/84) of GC samples and increased in 31.0% (26/84) compared with normal paracancerous tissues using immunohistochemical analysis. Low or unchanged miR-486-5p expression (P = 0.002), tumor stage (P = 0.001), tumor status (P = 0.001), node status (P = 0.001), tumor size (P = 0.004), and depth of tumor invasion (P = 0.013) were significant negative prognostic predictors for overall survival in patients with GC. After stratification according to American Joint Committee on Cancer (AJCC) stage, low/unchanged miR-486-5p expression remained a significant predictor of poor survival in stage II (P = 0.024) and stage III (P = 0.003). Cox regression analysis identified the following predictors of poor prognosis: tumor status (hazard ratio [HR], 7.19; 95% confidence interval [CI], 1.75–29.6; P = 0.006), stage (HR, 2.62; 95%CI, 1.50–4.59; P = 0.001), lymph node metastasis (HR, 2.52; 95% CI, 1.27–4.99; P = 0.008), low/unchanged miR-486-5p (HR, 2.47; 95% CI, 1.35–4.52; P = 0.003), high level of FGF9 (HR, 2.41; 95% CI, 1.42–4.09; P = 0.001) and tumor size (HR, 2.50; 95% CI, 1.30–4.82; P = 0.006). Low or unchanged expression of miR-486-5p compared with neighboring normal tissues was associated with a poor prognosis, while high expression was associated with a good prognosis in GC. miR-486-5p may thus be useful for evaluating prognosis and may provide a novel target treatment in patients with GC.

Sox17 promoter methylation in plasma DNA is associated with poor survival and can be used as a prognostic factor in breast cancer.

AbstractAberrant DNA methylation that leads to the inactivation of tumor suppressor genes is known to play an important role in the development and progression of breast cancer. Methylation status of cancer-related genes is considered to be a promising biomarker for the early diagnosis and prognosis of tumors. This study investigated the methylation status of the Sox17 gene in breast cancer tissue and its corresponding plasma DNA to evaluate the association of methylation levels with clinicopathological parameters and prognosis.The methylation status of the Sox17 gene promoter was evaluated with methylation-specific polymerase chain reaction (MSP) in 155 paired breast cancer tissue and plasma samples and in 60 paired normal breast tissue and plasma samples. Association of Sox17 methylation status with clinicopathological parameters was analyzed by &khgr;2 tests. Overall and disease-free survival (DFS) curves were calculated using Kaplan–Meier analysis, and the differences between curves were analyzed by log-rank tests.The frequency of Sox17 gene methylation was 72.9% (113/155) in breast cancer tissues and 58.1% (90/155) in plasma DNA. Sox17 gene methylation was not found in normal breast tissues or in their paired plasma DNA. There was a significant correlation of Sox17 methylation between corresponding tumor tissues and paired plasma DNA (r = 0.688, P < 0.001). Aberrant Sox17 methylation in cancer tissues and in plasma DNA was significantly associated with the tumor node metastasis stage (P = 0.035 and P = 0.001, respectively) and with lymph node metastasis (P < 0.001 and P = 0.001, respectively). Kaplan–Meier survival curves showed that aberrant Sox17 promoter methylation in cancer tissues and plasma DNA was associated with poor DFS (P < 0.005) and overall survival (OS) (P < 0.005). Multivariate analysis showed that Sox17 methylation in plasma DNA was an independent prognostic factor in breast cancer for both DFS (P = 0.020; hazard ratio [HR] = 2.142; 95% confidence interval [CI]: 1.128–4.067) and for OS (P = 0.001; HR = 4.737; 95% CI: 2.088–10.747).Sox17 gene promoter methylation may play an important role in breast cancer progression and could be used as a prognostic biomarker to identify patients at risk of developing metastasis or recurrence after mastectomy.

The anti-apoptotic and prognostic value of fibroblast growth factor 9 in gastric cancer.

Fibroblast growth factor (FGF) 9 is a member of the FGF family, which promotes carcinogenesis in some solid tumours. However, its biological and prognostic significance in gastric cancer (GC) is unclear. We examined FGF9 expression in 180 GC and corresponding non-tumorous gastric tissue samples by immunohistochemistry and evaluated its role in predicting tumour prognosis. Knockdown of FGF9 by siRNA inhibited cell growth and induced apoptosis in GC cell lines. Fifty of the 180 GC specimens (27.8%) had high FGF9 protein expression, whereas decreased or unchanged expression was observed in 130 cases (72.2%). High FGF9 expression was a significant predictor of poor survival (28.1 vs. 55.8 months, P < 0.001). After stratification according to AJCC stage, FGF9 remained a significant predictor of shorter survival in stage II (30.6 vs. 64.9 months, P < 0.001) and stage III GC (29.7 vs. 58.9 months, P < 0.001). Multivariate and univariate analysis showed that higher expression of FGF9 can be used as a predictor for poor prognosis (HR, 2.95; 95% CI, 1.97–4.41; P < 0.001; and HR, 2.94; 95% CI, 2.01–4.31; P < 0.001, respectively). FGF9 may provide the anti-apoptotic function and be useful as a novel independent marker for evaluating GC prognosis

Circulating tumor cells in breast cancer beyond the genotype of primary tumor for tailored therapy

Although TNM staging based on tumor, node lymph status and metastasis status—is the most widely used method in the clinic to classify breast cancer (BC) and assess prognosis, it offers limited information for different BC subgroups. Circulating tumor cells (CTCs) are regarded as minimal residual disease and are proven to have a strong relationship with BC. Detection of ≥5 CTCs per 7.5 mL in peripheral blood predicts poor prognosis in metastatic BC irrespective of other clinical parameters, whereas, in early‐stage BC, detection of CK19+ CTCs are also associated with poor prognosis. Increasing data and clinical trials show that CTCs can improve prognostic accuracy and help tailor treatment for patients with BC. However, heterogeneous CTCs in the process of an epithelial‐mesenchymal transition (EMT) in BC makes it a challenge to detect these rare cells. Moreover, the genotypic and phenotypic features of CTCs are different from primary BC tumors. Molecular analysis of CTCs in BC may benefit patients by identifying those amenable to tailored therapy. We propose that CTCs should be used alongside the TNM staging system and the genotype of primary tumor to guide tailored BC diagnosis and treatment.

miR-486-5p expression pattern in esophageal squamous cell carcinoma, gastric cancer and its prognostic value

Micro RNA (miR)-486-5p is often aberrantly expressed in human cancers. The aim of this study was to identify the prognostic value of miR-486-5p expression in digestive system cancers. Tissue microarrays were constructed with 680 samples including 185 esophageal squamous cell carcinomas (ESCCs), 90 gastric adenocarcinomas (GCs), and 60 digestive system cancer tissues from 10 ESCC, 10 GC, 10 colon, 10 rectum, 10 liver, 10 pancreatic cancer, and corresponding normal tissues. Twenty normal digestive system mucosa tissues from healthy volunteers were included as normal controls. In GC, miR-486-5p expression was decreased in 62.8% of cases (59/94), increased in 33.0% (31/94), and unchanged in 4.2% (4/94); in ESCC its expression was decreased in 66.2% (129/195), increased in 32.3% (63/195), and unchanged in 1.5% (3/195). Expression of miR-486-5p was decreased in 12, and increased in 8, of 20 cases of colon or rectum cancer; decreased in 6, and increased in 4, of 10 cases of liver cancer; and decreased in 8, and increased in 2, of 10 cases of pancreatic cancer. Multivariate and univariate regression analysis demonstrated that low/unchanged miR-486-5p predicted poor prognosis in ESCC (hazard ratio [HR], 4.32; 95% confidence interval [CI], 2.62–7.14; P < 0.001; HR, 3.88; 95% CI, 2.43–6.22; P < 0.001, respectively) and GC (HR, 2.46; 95% CI, 1.35–4.50; P = 0.003; HR, 2.55; 95% CI, 1.39–4.69; P = 0.002, respectively). MiR-486-5p might therefore be an independent tumor marker for evaluating prognosis in patients with ESCC or GC.

Synchronous primary cancers of the thyroid and breast: A case report and review of the literature.

The current report presents the case of a 41-year-old female exhibiting synchronous primary cancers of the thyroid and breast. Pathological examination of a tissue sample following biopsy identified papillary carcinoma of the thyroid and invasive ductal carcinoma of the breast to provide a definitive diagnosis of synchronous primary tumors. The patient underwent a modified radical mastectomy and total thyroidectomy. Following regular adjuvant chemotherapy with cyclophosphamide (800 mg), doxorubicin (100 mg) and paclitaxel (120 mg), once every three weeks for 3.5 months, oral levothyroxine and endocrinotherapy was recommended. Two years after the initial diagnosis, the patient was healthy with no disease recurrence. To the best of our knowledge, no association has been identified between the etiology and diagnoses of the two synchronous primary tumors. Thus, the aim of the current report was to improve the understanding of synchronous primary tumors of the thyroid and breast by presenting a review of the associated literature regarding breast and thyroid cancer. The mechanisms of synchronous neoplasms have only recently been elucidated, however, misdiagnosis is common. Clinicians are, therefore, advised to carefully examine patients with thyroid or breast cancer to avoid an incorrect or misdiagnosis. Furthermore, the present report aims to provide a reference for the cancer database, since the majority of analyses of rare diseases are derived from case reports. To improve the understanding of synchronous primary cancers of the thyroid and breast, an analysis of recent studies regarding the underlying mechanisms of synchronous primary cancers was also undertaken.

Loss of fibulin‑2 expression is involved in the inhibition of breast cancer invasion and forms a new barrier in addition to the basement membrane

Previous studies have demonstrated that fibulin-2 may facilitate cancer cell invasion and metastasis during tumor progression. In the present study, immunohistochemical analyses of fibulin-2 and collagen IV expression in 35 patients with breast cancer were performed to define their localization and association with breast cancer tissue. Fibulin-2 was revealed to be expressed in all tissues surrounding the breast ducts and blood vessels in normal breast tissue, while its expression was not integrated in invasive ductal carcinoma or terminal duct-lobular unit. In malignant breast tissue, collagen IV was integrated around the duct, while fibulin-2 was expressed around collagen IV and was incomplete. These results demonstrated that fibulin-2 was associated with breast cancer invasion. Fibulin-2 expression decreased prior to basement membrane (BM) degradation, indicating that fibulin-2 forms an additional barrier around the BM. Therefore, it was proposed that fibulin-2 composes the general BM, which differs from the traditional BM. These results provide insight into extracellular matrix components and the involvement of fibulin-2 in tumor invasion and metastasis. Fibulin-2 was involved in the process of breast cancer development. It performed an important role in prevention of cancer cell penetration and metastasis.

High expression of mir-25 predicting poor prognosis in gastric cancer

Aim: The aim of this study was to explore miR-25 expression pattern and its prognostic value in gastric carcinoma (GC). Methods: MiR-25 expression was detected using miRNA-locked nucleic acid in situ hybridization in 180 patients with GC undergoing surgery. Correlation with clinicopathological features and overall survival (OS) was analyzed. Results: MiR-25 expression was decreased in 10.0% (18/180) of GC, increased in 62.2% (112/180), and unchanged in 27.8% (50/180), compared to samples of morphologically normal tissue taken from the same patient (P < 0.001). Univariate analysis showed that high miR-25 expression, tumor stage, tumor status, node status, and tumor size were significant negative prognostic predictors for OS in patients with GC, and the results were shown as P < 0.001, P < 0.001, P = 0.002, P> 0.001, and P = 0.001, respectively. High miR-25 expression remained a significant predictor of shorter survival in stage II (n = 56, P = 0.015) and stage III (n = 92, P < 0.001) GC. Multivariate regression analysis demonstrated that tumor status (hazard ratio [HR]: 1.91; 95% confidence interval [CI]: 0.79-4.62; P = 0.151), stage (HR: 2.26; 95% CI: 1.30-3.94; P = 0.004), lymph node metastasis (HR: 1.40; 95% CI: 0.73-2.68; P = 0.309), high expression of miR-25 (HR: 2.39; 95% CI: 1.53-3.72; P < 0.001), and tumor size (HR: 2.29; 95% CI: 1.40-3.74; P = 0.001) predicted shorter OS. Conclusion: High expression of miR-25 was associated with decreased OS. Thus, miR-25 may be useful for prognosis evaluation and may provide a novel treatment target in patients with GC.