Cancer Biomarkers

Breast cancer is a worldwide leading cause of cancer mortality and it is associated with numerous tumor suppressor genes and oncogenes. Growing evidence exists that different KLFs play pivotal roles of in human malignancies. However, the function of KLFs in breast cancer development has remained uncovered.

To explore the potential prognostic biomarkers among KLFs in breast cancer.

In the present study, by using multiple large open databases, such as Oncomine database, Kaplan-Meier Plotter, and bc-GenExMiner online software, we deeply analyzed the expressions and clinical values about KLFs in patients with breast cancer.

KLF4/5/8/9/10/15 were significantly down-regulated in breast cancer samples. KLF11 exerts significantly negative effect on the prognosis of patients, whereas expressions of KLF4/15 were associated with better prognosis. Moreover, the vital genes KLF4/11/15 showed significant association with clinical parameters including age, estrogen receptor, progesterone receptor, epidermal growth factor receptor-2, Scarff-Bloom-Richardson grade, and Nottingham prognostic index.

Bioinformatics analysis suggested that KLF4/11/15, compared to other KLFs, might be potential prognostic indicators and treatment targets for breast cancer patients.

Metastatic gastric carcinoma (GC) is a typically incurable disease. The progression of anti-metastatic treatment is hampered because the underlying mechanisms regulating the metastasis of GC cell are not well illuminated.

Therefore, further elucidation of the molecular mechanism behind the metastatic traits of GC cells is needed for optimizing GC treatment.

The levels of GOLM1 and MMP13 in GC cells and tissues were measured by using qPCR assay. The growth of GC cells in vitro was detected using MTS and colony formation assays. The migration and invasion of GC cells was analyzed using wound healing test and Transwell invasion assay. The level of MMP13 in GC cell was measured using immunoblotting and the level of GOLM1 was measured using immunofluorescence staining. The role of GOLM1 on the distant metastasis of GC SGC7910 cell was analyzed using experimental metastasis assay. Transplanted tumor model was constructed to analyze the influence of GOLM1 on GC cell growth in vivo.

Here, we report that GOLM1 is over-expressed in GC and knockdown GOLM1 impairs the aggressive phenotypes of GC cell in vitro. Furthermore, downregulation of GOLM1 restrains the tumor growth of GC cell in nude mice. Nevertheless, upregulation of GOLM1 distinctly elevated the growth, migration ability and invasiveness of GC SGC7910 cell. Finally, GOLM1 increases the metastatic phenotypes of GC cell in a MMP13-dependent manner.

Altogether, this investigation demonstrates the crucial function of GOLM1 in the progression of GC, which indicating GOLM1 as a potential target for GC treatment.

: ACOT plays an important role in lipid metabolism and recent studies found that ACOT participates in some kinds of tumorigenesis. However, both the role of ACOT and its significance have not been revealed in AML. Therefore, we conduct this study in order to investigate the association between AML and ACOT, and hopefully contributed to the management of AML.

: One hundred and fifty-six AML patients were enrolled in our study whose data were derived from the Cancer Genome Atlas database. There were 85 patients who received only chemotherapy and other 71 patients underwent allo-HSCT.

: Patients in high ACOT7 group had a significant lower EFS and OS, while patients in high versus low expression levels of other types of ACOT showed no significant difference on the outcome. High level of ACOT7 related with poor outcome in both chemotherapy-only group and HSCT group.

: High expression level of ACOT7 indicates unfavorable outcome in AML patients. Allo-HSCT could not overcome the unfavorable effect of ACOT7 in these patients.

It has been documented that transient receptor potential melastatin 7 (TRPM7) plays a pivotal role in the development of multiple cancers. However, the role of TRPM7 in human colorectal cancer (CRC) is poorly understood. Therefore, the aim of this study was to investigate the expression and significance of TRPM7 in CRC.

In this study, TRPM7 expression was first investigated in Gene Expression Omnibus (GEO), and then validated it with the data from our medical center. CCK-8, colony survival, transwell, and flow cytometry assays were employed to evaluate the effects of TRPM7 knockdown on the CRC cell proliferation, migration, and invasion, as well as cell cycle and apoptosis.

We observed markedly increased TRPM7 expression in CRC tissues. CRC patients with high expression of TRPM7 suggested deeper tumor infiltration, positive lymph node metastasis, distant metastasis, and advanced clinical stage. In addition, TRPM7 was also overexpressed in CRC cell lines. Downregulated TRPM7 in vitro suppressed CRC cell proliferation, migration, and invasion, as well as triggered cell cycle arrest at the G0/G1 phase, reduced the S phase, and promoted apoptosis. Importantly, decreased TRPM7 in CRC cells reversed the epithelial-mesenchymal transition (EMT) status, accompanied by downregulation of N-cadherin and upregulation of E-cadherin.

Our study indicated that the expression of TRPM7 was positively correlated with tumor infiltration, lymph node metastasis, distant metastasis and clinical stage of CRC. Besides, decreased TRPM7 in vitro inhibited CRC cell proliferation, migration and invasion by modulating EMT.

To determine the utility of plasma microRNAs (miRNAs) as biomarkers in cervical cancer (CC).

Some studies were conducted about the specific expression of plasma miRNAs in the diagnosis of CC. Plasma samples of 97 CC patients and 87 normal controls (NCs) were used to identify dysregulation of miRNAs in the training, testing, and external validation phases. Receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) were used to evaluate the sensitivity and specificity of identified individual miRNAs and miRNA panels for the diagnosis of CC. Expression levels of specific miRNAs were also examined in plasma exosomes and tissue samples of CC patients.

Four plasma miRNAs (miR-146a-5p, miR-151a-3p, miR-2110 and miR-21-5p) which showed up-regulation were identified and validated in CC patients. A panel of the four miRNAs were constructed as potential diagnostic markers for CC. The AUCs of the panel of these four-miRNAs for the training, testing, and external validation phases were 0.911, 0.774, and 0.786, respectively. miR-146a-5p and miR-21-5p levels were all up-regulated in CC tissue specimens, whereas miR-146a-5p, miR-151a-3p, and miR-2110 levels were up-regulated in plasma exosomes.

The signature of the four-miRNAs identified in peripheral plasma is a promising novel biomarker for the diagnosis of CC.

The identification of high-sensitivity biomarkers for detection of hepatocellular carcinoma (HCC) from high-risk individuals is essential.

The present study was undertaken to identify and validate serum microRNAs (miRNAs) as potential biomarkers for hepatitis C virus (HCV)-related HCC.

Illumina sequencing was employed to screen the expression profiles of miRNAs in serum samples of HCV-related HCC patients and liver cirrhosis (LC) patients. RT-qPCR was used to confirm the altered miRNAs between the two groups. Moreover, candidate miRNAs were examined in serum samples of 40 HCC patients, 54 LC patients, 55 patients with chronic HCV hepatitis and 45 healthy controls. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the miRNAs for the detection of HCC.

Four miRNAs (miR-122-5p, miR-331-3p, miR-494-3p, miR-224-5p) were significantly increased and two miRNAs (miR-185-5p, miR-23b-3p) were significantly decreased in HCC patients compared to LC patients. ROC curve analysis demonstrated that the six miRNAs could be used as potential biomarkers for HCC detection. Combination of the six miRNAs could efficiently detect HCC in LC patients with the area under the ROC curve (AUC) of 0.995 and combination of the six miRNAs also provided high diagnostic accuracy (AUC = 0.961) for detection of HCC in non-HCC subjects.

The six serum miRNAs can be utilized as a surrogate and non-invasive biomarker for HCV-related HCC diagnosis.

Male breast cancer (MBC) is a rare and aggressive disease. Thus, identification of new therapeutic targets is crucial.

Our objective was to evaluate the protein expression of MARCKS (Myristoylated Alanine-Rich C-Kinase Substrate) in MBC and to investigate its prognostic value.

MARCKS protein expression in tumor and stromal cells was analyzed by immunohistochemistry (IHC) in a retrospective series of 96 pre-chemotherapy MBC samples and 80 normal breast samples, from Tunisian patients treated at Salah Azaiez Institute. Correlations were searched between MARCKS expression and clinicopathological features including overall survival (OS).

MARCKS was overexpressed in epithelial tumor cells in 66% of the MBC samples versus 26% of normal samples ( p = 1.40 × 10 - 7 ). Such positive MARCKS expression in epithelial tumor cells was associated with positive HER2 status ( p = 4.0 × 10 - 3 ). It was associated with shorter OS in uni-and multivariate analysis. By contrast, stromal IHC MARCKS expression was correlated only with tumor grade.

MARCKS tumor cell overexpression might in part explain the aggressiveness and the poor prognosis of MBC. MARCKS can represent a potential therapeutic target for MBC.

This study aimed to assess the diagnostic value of human epididymis protein 4 (HE4) in the pleural effusion of lung cancer patients.

HE4 protein in the pleural effusion of 60 lung cancer patients was measured by electrochemiluminescence, in parallel with those from 56 patients with benign lung disease, and the association with malignant pleural effusion was evaluated.

The level of HE4 in samples from lung cancer patients was significantly higher than the level for those with benign lung lesions ( P = 0.001) and patients with lung adenocarcinoma showed significantly higher levels of HE4 than those with squamous cell carcinoma and small cell carcinoma ( P = 0.002 and P = 0.034, respectively). Using an optimal threshold of 652.2 pmol/L, the HE4 level distinguished malignant lung cancer from benign lesions with a sensitivity of 78.3% and a specificity of 75.0%. Moreover, the HE4 level differentiated adenocarcinoma from benign lesions with a sensitivity of 75.9% and a specificity of 85.7% when a threshold of 744.05 pmol/L was used. However, there was no significant difference in the 2 year survival rates of lung cancer patients with high and low HE4 concentrations in pleural fluid ( P = 0.882). In addition, there was no significant difference in HE4 levels between tuberculous and inflammatory pleural effusions ( P = 0.309).

HE4 in the pleural fluid of lung cancer patients can be valuable in the diagnosis of malignant pleural effusion; however, it does not correlate with the prognosis of patients.