Lung Squamous Cell Carcinoma Samples Research Articles

Integrative and Comparative Genomic Analysis of Lung Squamous Cell Carcinomas in East Asian Patients

Lung squamous cell carcinoma (SCC) is the second most prevalent type of lung cancer. Currently, no targeted therapeutics are approved for treatment of this cancer, largely because of a lack of systematic understanding of the molecular pathogenesis of the disease. To identify therapeutic targets and perform comparative analyses of lung SCC, we probed somatic genome alterations of lung SCC by using samples from Korean patients. We performed whole-exome sequencing of DNA from 104 lung SCC samples from Korean patients and matched normal DNA. In addition, copy-number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated. This cancer cohort is characterized by a high mutational burden with an average of 261 somatic exonic mutations per tumor and a mutational spectrum showing a signature of exposure to cigarette smoke. Seven genes demonstrated statistical enrichment for mutation: TP53, RB1, PTEN, NFE2L2, KEAP1, MLL2, and PIK3CA). Comparative analysis between Korean and North American lung SCC samples demonstrated a similar spectrum of alterations in these two populations in contrast to the differences seen in lung adenocarcinoma. We also uncovered recurrent occurrence of therapeutically actionable FGFR3-TACC3 fusion in lung SCC. These findings provide new steps toward the identification of genomic target candidates for precision medicine in lung SCC, a disease with significant unmet medical needs.

Correlation of HPV-16/18 infection of human papillomavirus with lung squamous cell carcinomas in Western China

Prevalent inconsistency of human papillomavirus (HPV) infection in lung cancer was found among recent studies from different countries with racial and geographic variations. Even in Chinese populations, the prevalent discrepancy of HPV infection in lung cancer patients was also found with the geographic variations and tumor types. To study the difference of HPV-16/18 infection in lung squamous cell carcinomas and non-cancer controls, we conducted this study to verify whether there was a similar HPV infection prevalence pattern in lung squamous cell carcinoma patients from the Western part of China. Paraffin-embedded samples (180), of 72 lung squamous cell carcinomas, 37 lung adenocarcinomas and 71 non-cancer controls, were analyzed by INNO-LIPA Genotype polymerase chain reaction (PCR) and real-time PCR analysis. The data showed that 51.4% (37/72) of lung squamous cell carcinoma samples, 16.2% (6/37) of adenocarcinoma, and 22.5% (16/71) of non-cancer controls were HPV DNA positive. The risk of lung squamous cell carcinomas was 3.5 times higher among people HPV-positive (odds ratio 3.5, 95% CI 1.6-7.3, p<0.001) compared with the HPV- negative population. Adjusted by smoking status, the risk of lung squamous cell carcinomas was 3.5 times higher among people HPV-positive (odds ratio 3.5, 95% CI 1.7-7.5, p=0.001) compared with the HPV-negative population. The risk of lung squamous cell carcinomas was 16.9 times higher for patients with positive HPV-16 (odds ratio 16.9, 95% CI 3.8-75.3, p<0.0001) than negative HPV-16. Adjusted by smoking status, the risk of lung squamous cell carcinomas was 17.4 times higher among people HPV-16 positive (odds ratio 17.4, 95% CI 3.9-77.5, p<0.0001) compared with HPV-16 negative people. INNO-LIPA Genotype analysis revealed that the frequency of high risk HPV-16 and 18 genotype in lung squamous cell carcinoma cases appeared to be significant higher than that in the non-cancer controls (P<0.001), and the most frequent genotype was HPV-16 (21 cases), followed by HPV-18 (6 cases), HPV-16/18 (4 cases) in lung squamous cell carcinomas, respectively, and the majority genotype was HPV-6 (9 cases) in controls. The HPV-16 E2/E6 ratio was significantly lower than the unity, suggested that the main presence of integrated form of HPV-16 genome (16/27) may contribute more to lung squamous cell carcinomas, despite its viral load estimated to be only <1 to 2 copies per cell.