Analysis of the effect of different pathological subtypes to prognosis in stage I pulmonary adenocarcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the prognostic value of the new classification (proposed by International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society) in stage I pulmonary adenocarcinoma.</p><p><b>METHODS</b>Pathological slides of 328 cases of stage I pulmonary invasive adenocarcinoma were reviewed according to the new classification. The patients received operation in Department of Thoracic Surgery of Zhongshan Hospital affiliated to Fudan University from January 2005 to December 2009. There were 145 male and 183 female patients with an average age of (59 ± 10) years (ranging from 34 to 82 years). Clinical, pathological, and survival data were retrospectively analyzed. Kaplan-Meier method was used for analysis of survival, and Cox regression analysis was used for finding out prognostic factors.</p><p><b>RESULTS</b>Five-year progression-free survival rate and overall survival rate of lepidic-predominant subtype were both 100%. Five-year progression-free survival rate of patients with micropapillary component (49.3%) was significantly lower than that of patients without micropapillary component (75.4%, χ² = 8.154, P = 0.004). Regression analysis showed that tumor size is an independent prognostic factor of death (HR = 1.967, 95% CI: 1.507 to 2.567, P = 0.000) and recurrence (HR = 1.796, 95% CI: 1.469 to 2.198, P = 0.000). In subgroup analysis, the presence of solid component (HR = 1.985, 95% CI: 1.013 to 3.888, P = 0.046) and tumor size (HR = 1.941, 95% CI: 1.455 to 2.589, P = 0.000) were independent prognostic factors of recurrence for stage IB pulmonary adenocarcinoma.</p><p><b>CONCLUSIONS</b>The new classification of adenocarcinoma is of prognostic value in stage I pulmonary adenocarcinoma. The presence of solid or micropapillary component impacts on survival. Detailed record of each component in tumor is necessary.</p>

Validation and target gene screening of hsa-miR-205 in lung squamous cell carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Lung cancers are classified as squamous cell carcinoma (SQ), adenocarcinoma (AC) and small cell lung carcinoma (SCLC). SQ is the major subtype of lung cancer. Currently, there are no targeted therapies for SQ due to lack of understanding its driving oncogenes. In this study, we validated an SQ specific biomarker hsa-miR-205 in Chinese patients with lung cancer and screened its candidate target genes for further functional studies to enrich knowledge in SQ target therapies.</p><p><b>METHODS</b>Quantitative reverse-transcription PCR (quantitative RT-PCR) was performed on 197 macro-dissected (cancerous cells >75%) surgical lung tissues (45 SQ, 44 AC, 54 SCLC and 54 adjacent normal tissues) to validate the expression profiles of miR-205. Furthermore, the targets of this microRNA were predicted through the gateway miRecords and mapped to lung cancer-associated pathways using the KEGG (Kyoto Encyclopedia of Genes and Genomes) database. Then quantitative RT-PCR was performed on an independent cohort of 44 snap-frozen surgical lung tissues to concurrently assess the expression profiles of miR-205 and its 52 putative targeted genes.</p><p><b>RESULTS</b>MicroRNA-205 yielded high diagnostic accuracy in discriminating SQ from AC with an area under the curve (AUC) of 0.985, and discriminating SQ from SCLC with an AUC of 0.978 in formalin-fixed paraffin-embedded (FFPE) surgical lung tissues. Predicted targets of miR-205 were associated with 52 key members of lung cancer signaling pathways. Ten target genes (ACSL1, AXIN2, CACNA2D2, FOXO3, PPP1R3A, PRKAG3, RUNX1, SMAD4, STK3 and TBL1XR1) were significantly down-regulated in SQ and had a strong negative correlation with miR-205, while one target gene (CDH3) was up-regulated in SQ and exhibited a strong positive correlation with miR-205.</p><p><b>CONCLUSIONS</b>We confirmed the high diagnostic accuracy of miR-205 in discriminating SQ from AC and SCLC in Chinese patients. Moreover, we identified 11 significant target genes of miR-205 which could be used for further functional studies as the basis for the development of SQ targeted therapies.</p>