Long noncoding RNA EPB41L4A-AS1 functions as an oncogene by regulating the Rho/ROCK pathway in colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. In terms of cancer-related death, colon cancer ranks second and third among men and women, respectively, and the incidence is increasing annually. Accumulating evidence have indicated that long noncoding RNA (lncRNA) plays an important role in tumorigenesis. In this study, we found that lncRNA EPB41L4A-AS1 was highly expressed in CRC tissues and was associated with poor prognosis and tumor metastasis in patients with CRC. In vitro studies showed that the knockdown of EPB41L4A-AS1 inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition of CRC cells. Mechanically, we found that EPB41L4A-AS1 may participate in the development of CRC by activating the Rho/Rho-associated protein kinase signaling pathway. Collectively, these results demonstrated that EPB41L4A-AS1 can promote the proliferation, invasion, and migration of CRC, and it may be a novel biomarker for the diagnosis and targeted treatment of CRC.

Detection of Colorectal Cancer in Circulating Cell-Free DNA by Methylated CpG Tandem Amplification and Sequencing.

BACKGROUND: Aberrant DNA hypermethylation of CpG islands occurs frequently throughout the genome in human colorectal cancer (CRC). A genome-wide DNA hypermethylation analysis technique using circulating cell-free DNA (cfDNA) is attractive for the noninvasive early detection of CRC and discrimination between CRC and other cancer types. METHODS: We applied the methylated CpG tandem amplification and sequencing (MCTA-Seq) method, with a fully methylated molecules algorithm, to plasma samples from patients with CRC (n = 147) and controls (n = 136), as well as cancer and adjacent noncancerous tissue samples (n = 66). We also comparatively analyzed plasma samples from patients with hepatocellular carcinoma (HCC; n = 36). RESULTS: Dozens of DNA hypermethylation markers including known (e.g., SEPT9 and IKZF1) and novel (e.g., EMBP1, KCNQ5, CHST11, APBB1IP, and TJP2) genes were identified for effectively detecting CRC in cfDNA. A panel of 80 markers discriminated early-stage CRC patients and controls with a clinical sensitivity of 74% and clinical specificity of 90%. Patients with early-stage CRC and HCC could be discriminated at clinical sensitivities of approximately 70% by another panel of 128 markers. CONCLUSIONS: MCTA-Seq is a promising method for the noninvasive detection of CRC.

[Epigenetic research progress in colorectal cancer].

Colorectal cancer is one of the common malignant tumors, which seriously threatens human health. Its morbidity and mortality rank the third and the second among all malignant tumors. The progress of colorectal cancer is a complex process involving the accumulation of genetic and epigenetic changes. Epigenetic changes of colorectal cancer mainly include DNA methylation, histone modification, non-coding RNAs (such as microRNAs and lncRNAs), which are of great significance to early diagnosis and prognosis evaluation, and to chemosensitivity assessment for colorectal cancer, providing a new thought for the treatment of colorectal cancer.

Protein S100-A8: A potential metastasis-associated protein for breast cancer determined via iTRAQ quantitative proteomic and clinicopathological analysis.

Breast cancer is the most common malignancy in females, with metastasis of this type of cancer frequently proving lethal. However, there are still no effective biomarkers to predict breast cancer metastasis. The aim of the present study was, therefore, to analyze breast cancer metastasis-associated proteins and evaluate the association between protein S100-A8 and the prognosis of breast cancer. The isobaric tags for relative and absolute quantitation (iTRAQ) proteomic technique was used to analyze the differential expression of proteins between fresh primary breast tumor (PBT) tissue and fresh paired metastatic lymph nodes (PMLN) tissue. Subsequently, immunohistochemical staining was used to locate and assess the expression of protein S100-A8 in benign breast disease (n=15), primary breast cancer with (n=109) or without (n=83) metastasis, and in paired metastatic lymph nodes (n=109) formalin fixed paraffin embedded (FFPE) tissue. Staining scores were evaluated and the association between protein S100-A8 expression levels and the clinicopathological characteristics of 192 patients with breast cancer were evaluated using the χ2 test. Kaplan-Meier and Cox hazards regression analyses were utilized to investigate the association between the expression of protein S100-A8 and the prognosis of patients with breast cancer. A total of 4,837 proteins were identified using the iTRAQ proteomic technique. Among these proteins, 643 differentially expressed proteins were revealed. Protein S100-A8 expression levels were identified to differ between PBT and PMLN tissues. Immunohistochemical staining suggested a significant difference between NMBT and PMLN (P=0.002), and also between PBT and PMLN (P<0.001). Cox hazards regression model analyses suggested that histological grade (P=0.031) and nodal status (P=0.001) were risk factors for lymph nodes metastasis of breast cancer. Kaplan-Meier analyses revealed no significant relationship between protein S100-A8 expression level and overall survival rate of patients with breast cancer. In conclusion, by using the iTRAQ proteomic technique and immunohistochemistry staining, it was identified that protein S100-A8 may be associated with lymph nodes metastasis of breast cancer and be a marker for progression of breast cancer.