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microRNA expression spectrum with non- small cell lung cancer clinical features and prognosis

Author: TanXiaoGang
Tutor: HeJie
School: Peking Union Medical College , China
Course: Oncology
Keywords: microRNA Non - small cell lung cancer Lung cancer cells miRNA Lung squamous cell carcinoma Microarray Lung adenocarcinoma cell Soft agar Protein Adjacent tissues Therapeutic targets Smoking index Gene expression profiling Tumor classification Tumorigenesis Timing regulation Oncogene Targeted therapy Colony formation Graduate Dissertation
CLC: R734.2
Type: PhD thesis
Year: 2009
Downloads: 616
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Abstract

Lung cancer has the highest world-wide cancer mortality. Patients with apparently similar lung cancers may experience very different clinical outcomes, and it is often difficult to predict a patient’s prognosis. Tumor-node-metastasis (TNM) classification allows diagnosis of the tumor, it provides little therapeutic biological information, such as the metastatic potential or the sensitivity or resistance of the tumor to radiotherapy and chemotherapy. MicroRNAs (miRNAs) are a species of small non-coding single-stranded RNA of about 21 nucleotides that, through partial sequence homology, may interact with the 3’-untranslated region of target mRNA molecules. Recent evidence has shown that miRNA may function as tumor supressors or oncogenes, and alterations in miRNA expression may play a critical role in the initiation and progression of a number of cancers. Therefore, miRNA expression profiles may also be useful for diagnosis of lung cancer, for sub-type classification, or for predicting patient prognosis and guiding personalized disease management. While microRNA expression profiling has recently been used to characterize the prognosis for patients with adenocarcinoma of lung cancer, description of the microRNA patterns in lung cancer, especially the prognosis for squamous cell carcinoma of lung cancer is lacking.To define the microRNA expression patterns associated with lung cancer and the microRNA associated with prognosis for squamous cell carcinoma of lung cancer. MicroRNA microarray expression profiling of tumors and paired adjacent normal tissues was performed on a cohort of 116 patients,60 squamous cell carcinomas,43 adenocarcinomas and 13 small cell lung cancers, recruited between 2000 and 2002. We evaluated microRNA associations with cancer versus adjacent normal tissue, clinicopathological status. Survival association was validated in an independent cohort of 20 squamous cell carcinomas, using quantitative reverse transcription polymerase chain reaction assays. Five microRNAs classifier could distinguish malignant lung cancer lesions from adjacent normal tissues. Some miRNAs showed correlations with several different clinicopathological parameters. High hsa-miR-31 expression was associated with poor survival in squamous cell carcinoma of lung cancer. High hsa-mir-20a and low hsa-mir-126 expression correlated with poor survival of SCLC. Lung cancer may have a distinct miRNA expression pattern that may differentiate it from normal tissue and clinicopathological status. High hsa-miR-31 expression is associated with poor survival outcome.Current therapies for NSCLC patients are inefficient due to the lack of diagnostic and therapeutic markers. The phospho-Ser/Thr-Pro specific prolyl-isomerase Pin1 is overexpressed in many different cancers, including NSCLC, and may possibly be used as a target for cancer therapy. To validate the oncogenic potential of Pinl in lung cells, we down-regulated Pinl by RNA interference in H1299 cells. Retrovirus-mediated siRNA targeting of Pinl resulted in the stable suppression of both cell growth, anchorage-independent growth in soft agar and tumorigenic including cell migration, invasion in H1299 cells. Pinl expression may be an unfavorable prognostic factor in patients of NSCLC patients, and these results indicate that Pinl may have a role in tumor development and metastasis and thus could serve as a novel target for treatment of NSCLC.

microRNA expression spectrum with non- small cell lung cancer clinical features and prognosis

Abstract

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