Cancer Biomarkers

To investigate the role of miR-337-3p targeting Rap1A in modulating proliferation, invasion, migration and apoptosis of cervical cancer cells.

The expression levels of miR-337-3p and Rap1A in cervical cancer tissues and normal tissues were evaluated through quantitative Real-time PCR (qRT-PCR) and Western blotting; and correlations of miR-337-3p with clinicopathological characteristics and prognosis of patients were also analyzed. Besides, human cervical cancer cell line HeLa cells were randomly divided into five groups (Mock, NC, miR-337-3p mimic, Rap1A, and miR-337-3p mimic + Rap1A groups). CCK-8 assay was utilized to measure cell proliferation, flow cytometry to evaluate cell apoptosis, and wound-healing and Transwell assays to detect cell migration and invasion.

Cervical cancer tissues presented a significant decrease in miR-337-3p and a remarkable increase in Rap1A protein. Besides, the expression levels of miR-337-3p and Rap1A were closely related to the major clinicopathological characteristics of cervical cancer; and patients with high-miR-337-3p-expression had the higher 5-year survival rate (all p < 0.05). When compared to Mock group, cells in miR-337-3p mimic group were suppressed in proliferation, migration, and invasion, but significantly promoted in apoptosis; meanwhile, cells in the Rap1A group showed changes in a completely opposite trend (all p < 0.05). Moreover, Rap1A can reverse the effect of miR-337-3p mimic on cell proliferation, invasion, migration and apoptosis (all p < 0.05).

MiR-337-3p was discovered to be decreased in cervical cancer, and miR-337-3p up-regulation may inhibit the proliferation, migration and invasion and promote the apoptosis of cervical cancer cells via down-regulating Rap1A.

Colorectal cancer (CRC) is one of the most prevalent cancers and microRNAs are involved in colorectal carcinogenesis and progression. The role of our candidate microRNAs (miR-143-3p, -424-5p, -212-3p and -34a-3p) have been investigated in various cancers.

The aim of the current study was to evaluate expression levels of microRNAs (miR-143-3p, -424-5p, -212-3p and -34a-3p) in the sera of patients with CRC in order to identify potential non-invasive biomarker for CRC and investigate the relationship between their expression and clinicopathological features of CRC.

The serological expression of candidate microRNAs were measured in 124 participants, including 62 CRC patients and 62 healthy controls and the serum expression levels of candidate miRNAs were quantified by stemloop reverse transcriptionquantitative polymerase chain reaction.

In the present study, results showed a significant upregulation expression level of miR-424-5p ( P < 0.001) and decreased expression level of miR143-3p was observed in the sera of patients with CRC ( P < 0.001). Receiver operating characteristic (ROC) curve analysis demonstrated the area of miR-424-5p and miR-143-3p under the ROC curve for CRC diagnosis were 0.703 and 0.724 respectively ( P < 0.001). In addition, down expression of miR-143-3p was significantly associated with tumor size ( P = 0.005) and lymph node metastasis ( P = 0.020) in CRC patients.

The present investigation suggested that low expression of miR-143-3p and increasing level of miR-424-5p in CRC patients may play an important role in development of CRC and they could function as potential non-invasive biomarkers for CRC.

Circulating microRNAs (miRNAs) have become increasingly appreciated in the diagnosis and prognosis of colorectal cancer (CRC).

The aim of this study was to assess the potential diagnostic and prognostic significance of serum miR-30a-5p as a potential biomarker.

The expression levels of serum miR-30a-5p were measured in 138 cases with CRC, 50 cases with benign lesions (colorectal adenoma and polyps) and 60 healthy volunteers by quantitative real time polymerase chain reaction (qRT-PCR).

The results showed that serum miR-30a-5p levels were frequently downregulated in patients with CRC and benign lesions in comparison with normal controls. Moreover, serum miR-30a-5p levels in early-stage CRC patients were significantly increased after surgery. Receiver-operating characteristic (ROC) curve analysis demonstrated serum miR-30a-5p could well distinguish CRC patients, early-stage CRC patients from healthy controls with a relative high value of area under the curve (AUC). Furthermore, low serum miR-30a-5p expression was more frequently occurred in CRC patients with aggressive clinical variables. Additionally, CRC patients exhibiting high serum miR-30a-5p expression had significantly prolonged overall survival than those exhibiting low expression. Finally, both univariate and multivariate analyses revealed that serum miR-30a-5p expression was an independent prognostic factor for overall survival in CRC patients.

Collectively, these findings suggested serum miR-30a-5p might act as a novel biomarker for the diagnosis and prognosis of CRC.

Previous studies have demonstrated that platelets play an important role in growth, invasion, and angiogenesis of a variety of tumors. Nevertheless, the prognostic role of platelet indices in hepatocellular carcinoma (HCC) has not been explored. The aim of this study was to explore the association between platelet indices and prognosis in HCC.

A total of 260 patients with HCC between January 2009 and December 2015 were retrospectively analyzed. The optimal platelet distribution width (PDW) cutoff value is identified by the receiver operating characteristic curve (ROC) curve. The relationship between PDW and clinicopathological features was assessed. The prognostic effects of PDW were assessed by using the Kaplan-Meier method and Cox regression model.

Elevated PDW level was significantly associated with portal hypertension, vascular invasion, and Child-Pugh grade. In addition, survival curve indicates that patients with high PDW levels have a worse prognosis than patients with low PDW levels ( P < 0.001). Multivariate Cox regression analysis identified PDW as an independent factor of prognosis in HCC patients (hazard ratio: 4.460, 95% confidence interval: 2.308–8.619, P < 0.001).

Elevated PDW may be a novel marker for predicting the prognosis of HCC, but further research is needed to validate our conclusions.

Endometrial cancer is one of the most common tumor of the woman genital organs.

The goal of this study was to determine the lipocalin-2 levels in patients with endometrial cancer compared to those with normal endometrium or mild endometrial pathologies.

Study included 123 patients with BMI > 21 kg/m 2 who were admitted due to abnormal bleeding, in which 52 patients with endometrial cancer. The NGAL, CA125, HE4 serum levels were determined for all patients.

Significantly lower median NGAL serum levels were found in a group of patients with normal endometrium compared to the endometrial cancer group, p = 0.006. NGAL protein area under ROC curves value as a diagnostic test, differentiating between endometrial cancer and other benign changes endometrium is AUC – 0.81 ( p < 0.00001). The NGAL protein had a high sensitivity in all patients included in the analysis: 84% vs. 82% in pre-menopausal patients, and 81% in postmenopausal women with a specificity of 78%, 80% and 87%, respectively. The independent variable for FIGO and model logistic regression proves that NGAL is statistically significant ( p = 0.000602), the odds ratio is 3.66. The model for grading shows, that NGAL increase by one ng/ml increases risk chances by 2.32 times in diagnosis with less cancer differentiation.

Our preliminary studies demonstrate that lipocalin-2 may be of value in the diagnostics of uterine body cancers.

For patients with pancreatic cancer, a preoperative assessment of prognosis is crucial to predict cancer recurrence and to prepare a postoperative adjuvant strategy and appropriate patient-counsel.

We evaluated the prognostic predictive power of complement factor B (CFB) by comparing it to that of other known tumor markers in resected pancreatic cancer patients.

From 2012 to 2013 period, we retrospectively reviewed the plasma CFB levels of 35 pancreatic cancer patients. The patients were divided into two groups according to serologic CFB values. Disease-free survival (DFS) and overall survival (OS) rates were analyzed.

Based on the cut-off values of plasma CFB, 15 patients were placed in the low CFB group and the other 20 patients were placed in the high CFB group. There was a significant difference in DFS between the two groups (Low CFB vs. High CFB: 36.9 months vs. 13.9 months, p : 0.007). In the OS analysis, there was also a significant difference in the survival rates of the two groups (Low CFB vs. High CFB: 49.7 months vs. 29.0 months, p : 0.048).

Preoperative plasma CFB can be used to predict the prognosis of resectable pancreatic cancers; it outperforms both CA 19-9 and CEA.

Malignant peripheral nerve sheath tumor (MPNST) is rare, aggressive soft tissue sarcoma which may affect children.

We aimed to assess prognostic significance of immunohistochemical (IHC) markers, osteopontin, fibronectin, survivin, cyclin D1 and p53, in pediatric MPNST.

A total of 26 pediatric MPNST patients were enrolled in the current study with a median follow-up of 51 months. IHC staining using commercially available monoclonal antibodies were employed to detect analyzed antigens on tissue microarrays. Eventually, all markers were subclassified to high (H) and low (L) expression categories in all analyzed tumors.

High IHC expressions of survivin, cyclin D1, osteopontin, fibronectin, and p53 were detected in 18 (69.2%), 13 (50%), 16 (61.5%), 16 (61.5%), and 13 (50%) tumors, respectively. A significant correlation was demonstrated between cyclin D1 and osteopontin ( p = 0.004). Both markers were associated with neurofibromatosis type 1 (NF1) status ( p = 0.041 and p = 0.037, respectively). H-fibronectin was more prevalent in deeply located tumors ( p = 0.046). None of the markers was associated with IRS stage, age at diagnosis, and tumor size. Univariate analysis identified IRS stage, regional lymph node metastases, NF1, and cyclin D1 as variables associated with overall survival (OS), whereas tumor depth, osteopontin, and cyclin D1 – for relapse-free survival (RFS). Subsequent multivariate analysis identified cyclin D1 and p53 as independent variables predicting RFS, whereas cyclin D1 and regional lymph nodes status were independent predictors for OS.

Dysregulation of DNA polymerase iota (Pol ι ) in breast cancer might contribute to the accumulation of genomic mutations and promotes breast cancer progression. In this study we explored the clinical relevance and biological function of Pol ι in breast cancer.

qRT-PCR was used to determine the expression levels of Pol ι in 31 breast cancer tissues. Then the stable overexpression of Pol ι and knockdown of Pol ι breast cancer cell lines were constructed. Wound-healing assay and transwell assay were performed to evaluate cell migratory and invasiveness, respectively. Signaling pathway was analyzed by western blot.

The expression levels of Pol ι is overexpressed in breast cancer tissues and significantly higher in breast cancer tissues with lymph node metastasis compared to those without lymph node metastasis. Elevated Pol ι expression promoted migratory and invasiveness of breast cancer cells. Signaling pathway analysis indicated EGFR-ERK cascade works as a mediator of Pol ι -induced EMT of breast cancer cells.

These data demonstrate the underlying mechanism by which Pol ι promotes breast cancer progression, suggesting that Pol ι may be a potential therapeutic target against breast cancer.