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BackgroundNumerous efforts have been made to elucidate the etiology and improve the treatment of lung cancer, but the overall five-year survival rate is still only 15%. Although cigarette smoking is the primary risk factor for lung cancer, only 7% of female lung cancer patients in Taiwan have a history of smoking. Since cancer results from progressive accumulation of genetic aberrations, genomic rearrangements may be early events in carcinogenesis.ResultsIn order to identify biomarkers of early-stage adenocarcinoma, the genome-wide DNA aberrations of 60 pairs of lung adenocarcinoma and adjacent normal lung tissue in non-smoking women were examined using Affymetrix Genome-Wide Human SNP 6.0 arrays. Common copy number variation (CNV) regions were identified by ≥30% of patients with copy number beyond 2 ± 0.5 of copy numbers for each single nucleotide polymorphism (SNP) and at least 100 continuous SNP variant loci. SNPs associated with lung adenocarcinoma were identified by McNemar’s test. Loss of heterozygosity (LOH) SNPs were identified in ≥18% of patients with LOH in the locus. Aberration of SNP rs10248565 at HDAC9 in chromosome 7p21.1 was identified from concurrent analyses of CNVs, SNPs, and LOH.ConclusionThe results elucidate the genetic etiology of lung adenocarcinoma by demonstrating that SNP rs10248565 may be a potential biomarker of cancer susceptibility.

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Lung cancer has become the leading cause of cancer death in Taiwan and in most countries. Although smoking has been the major risk factor for lung cancer, less than 20% smokers develop lung cancer. In Taiwan, only about 50% of lung cancer cases were related to smoking, while more than 90% lung cancer females were non-smokers. In this study, we collected gene expression microarrays to investigate the pathogenesis process. One hundred and twenty lung tumor samples and their normal counterparts from non-smoking females were collected from National Taiwan University Hospital and Taichung Veterans General Hospital. RNAs from 60 paired samples were examined using Affymetrix Human U133 plus2.0 microarray. Paired t-tests were used to identify differentially expressed genes between tumor and normal tissues. The preliminary results showed there were 791 differentially expressed genes (p-value < 10−14). Ingenuity Pathway Analysis (IPA) was utilized for further functional and pathway analyses on these genes, and the axon guidance signaling pathway was the most significantly enriched pathway. Among genes in the axon guidance signaling pathway, SEMA5A was chosen for further investigation because it was the most significant down-regulated gene in tumor tissue. Its down-regulation was validated by both real-time PCR and immunohistochemistry (IHC). Furthermore, Kaplan-Meier survival analysis showed that patients with low SEMA5A expression had poor overall survival as compared to those who had high SEMA5A expression. This significant association was also observed in two published studies. Therefore, these results indicated that the SEMA5A may play an important role in the carcinogenesis and can be a potential prognosis biomarker for non-smoking lung cancer females in Taiwan. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2944.

Changes in the oral microbiome are associated with oral squamous cell carcinoma (OSCC). Oral microbe-derived signatures have been utilized as markers of OSCC. However, the structure of the oral microbiome during OSCC recurrence and biomarkers for the prediction of OSCC recurrence remains unknown. To identify OSCC recurrence-associated microbial biomarkers for the prediction of OSCC recurrence, we performed 16S rRNA amplicon sequencing on 54 oral swab samples from OSCC patients. Differences in bacterial compositions were observed in patients with vs without recurrence. We found that Granulicatella, Peptostreptococcus, Campylobacter, Porphyromonas, Oribacterium, Actinomyces, Corynebacterium, Capnocytophaga, and Dialister were enriched in OSCC recurrence. Functional analysis of the oral microbiome showed altered functions associated with OSCC recurrence compared with nonrecurrence. A random forest prediction model was constructed with five microbial signatures including Leptotrichia trevisanii, Capnocytophaga sputigena, Capnocytophaga, Cardiobacterium, and Olsenella to discriminate OSCC recurrence from original OSCC (accuracy = 0.963). Moreover, we validated the prediction model in another independent cohort (46 OSCC patients), achieving an accuracy of 0.761. We compared the accuracy of the prediction of OSCC recurrence between the five microbial signatures and two clinicopathological parameters, including resection margin and lymph node counts. The results predicted by the model with five microbial signatures showed a higher accuracy than those based on the clinical outcomes from the two clinicopathological parameters. This study demonstrated the validity of using recurrence-related microbial biomarkers, a noninvasive and effective method for the prediction of OSCC recurrence. Our findings may contribute to the prognosis and treatment of OSCC recurrence.