Predictive Markers For Diagnosis Research Articles

Pathogenetic and therapeutic roles of non-coding RNAs on major depressive disorder

The major depressive disorder (MDD) affecting a large amount of population still has unknown neurobiological mechanisms and dissatisfactory treatment response.Given the urgently need for effective predictive markers for diagnosis and treatment, epigenetic studies of neuropsychiatric disorders including non-coding RNAs (ncRNAs) expand the research.Non-coding RNAs including microRNA, long noncoding RNA and circular RNA, may play important roles on neural differentiation, synaptic plasticity and central neurological reaction of stress during the course of antidepressant treatment.The current knowledge was summarized about posttranscriptional regulation of ncRNAs in major depression and discussed the potential biomarker value of ncRNAs for treatment evaluation in the context of individualized treatment. Key words: Non-coding RNA; Major depressive disorder; Antidepressant; Treatment

E2F1 promote the aggressiveness of human colorectal cancer by activating the ribonucleotide reductase small subunit M2

As the ribonucleotide reductase small subunit, the high expression of ribonucleotide reductase small subunit M2 (RRM2) induces cancer and contributes to tumor growth and invasion. In several colorectal cancer (CRC) cell lines, we found that the expression levels of RRM2 were closely related to the transcription factor E2F1. Mechanistic studies were conducted to determine the molecular basis. Ectopic overexpression of E2F1 promoted RRM2 transactivation while knockdown of E2F1 reduced the levels of RRM2 mRNA and protein. To further investigate the roles of RRM2 which was activated by E2F1 in CRC, CCK-8 assay and EdU incorporation assay were performed. Overexpression of E2F1 promoted cell proliferation in CRC cells, which was blocked by RRM2 knockdown attenuation. In the migration and invasion tests, overexpression of E2F1 enhanced the migration and invasion of CRC cells which was abrogated by silencing RRM2. Besides, overexpression of RRM2 reversed the effects of E2F1 knockdown partially in CRC cells. Examination of clinical CRC specimens demonstrated that both RRM2 and E2F1 were elevated in most cancer tissues compared to the paired normal tissues. Further analysis showed that the protein expression levels of E2F1 and RRM2 were parallel with each other and positively correlated with lymph node metastasis (LNM), TNM stage and distant metastasis. Consistently, the patients with low E2F1 and RRM2 levels have a better prognosis than those with high levels. Therefore, we suggest that E2F1 can promote CRC proliferation, migration, invasion and metastasis by regulating RRM2 transactivation. Understanding the role of E2F1 in activating RRM2 transcription will help to explain the relationship between E2F1 and RRM2 in CRC and provide a novel predictive marker for diagnosis and prognosis of the disease.

Prognostic significance of matrix metalloproteinase‐2, ‐8, ‐9, and ‐13 in oral tongue cancer

Oral tongue squamous cell carcinoma (OTSCC) often metastasizes to cervical lymph nodes. Mechanisms of this disease progression are not fully known. We aimed at finding new predictive markers for diagnosis and disease monitoring. Seventy-three consecutive T1N0M0 and T2N0M0 OTSCC patients treated at Helsinki University Central Hospital, Helsinki, Finland, in 1992-2002 were included. Tissue array blocks were prepared from primary tumors and immunostained. Immunoexpression of matrix metalloproteinase (MMP)-2, -8, -9, and -13 was compared with patient characteristics and outcome. Nuclear expression of MMP-13, but not cytoplasmic expression of MMP-2, -8, and -9, was associated with invasion depth (P = 0.017) and tumor size (P = 0.008). Furthermore, high nuclear MMP-13 expression was predictive of poor outcome (P = 0.042). Our results suggest that especially MMP-13 may be regarded as a prognostic biomarker in OTSCC.

Recognition of potential predictive markers for diagnosis in Korean serous ovarian cancer patients at stage IIIc using array comparative genomic hybridization with high resolution

Ovarian cancer is the second most frequently diagnosed gynecologic malignancy, and causes higher mortality than any other cancer in the reproductive system. Recognizing predictive markers of development and progression of this cancer would facilitate to individualize therapy and improve survival of ovarian cancer patients. Detection of genetic aberrations using array based comparative genomic hybridization (array CGH) has been implicated as one of important tools for identifying diagnostic and prognostic markers in various cancers, leading to the interesting study that exploration of copy number alterations in serous ovarian cancer at IIIc stage with the ultimate goal to discover potential predictive markers. To gain the best opportunities for exploring genomic imbalance involved in modulation of cancer development and progression, homogenous samples were selected as concerning with histology and stage in which we applied the array CGH with high resolution of one million formats. Here, the array CGH analysis obviously revealed significant DNA copy number changes (gain and loss) in Korean ovarian cancer patients at serous histological IIIc stage. We discovered DNA copy number gain in chromosome 6p22.3 whereas DNA copy number loss in chromosome 8p21.1-p12 and chromosome 11p15.4, with relatively high frequency of genomic alteration (83.3%). Upon these chromosomal regions, we eventually identified 32 genes including DUSP4, ID4, NRG1, and RRM1. We also classified their functions by gene ontology (GO) analysis using DAVID program and consequently demonstrated various interesting GO terms including biological regulation and positive regulation of cell growth. Taken together, these identified genes might be considered as potential predictive markers for further target-based strategies for diagnosis in Korean ovarian cancer patients at serous histological IIIc stage. These studies might also help understanding of tumorigenesis and the progression of ovarian carcinomas, in the aspect of genetic variations.