An Oral Microbial Biomarker for Early Detection of Recurrence of Oral Squamous Cell Carcinoma.

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.

SNP rs10248565 in HDAC9 as a novel genomic aberration biomarker of lung adenocarcinoma in non-smoking women.

BACKGROUND: Numerous 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. RESULTS: In 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. CONCLUSION: The results elucidate the genetic etiology of lung adenocarcinoma by demonstrating that SNP rs10248565 may be a potential biomarker of cancer susceptibility.

Use of germline polymorphisms in predicting concurrent chemoradiotherapy response in esophageal cancer.

PURPOSE: To identify germline polymorphisms to predict concurrent chemoradiation therapy (CCRT) response in esophageal cancer patients. MATERIALS AND METHODS: A total of 139 esophageal cancer patients treated with CCRT (cisplatin-based chemotherapy combined with 40 Gy of irradiation) and subsequent esophagectomy were recruited at the National Taiwan University Hospital between 1997 and 2008. After excluding confounding factors (i.e., females and patients aged ≥70 years), 116 patients were enrolled to identify single nucleotide polymorphisms (SNPs) associated with specific CCRT responses. Genotyping arrays and mass spectrometry were used sequentially to determine germline polymorphisms from blood samples. These polymorphisms remain stable throughout disease progression, unlike somatic mutations from tumor tissues. Two-stage design and additive genetic models were adopted in this study. RESULTS: From the 26 SNPs identified in the first stage, 2 SNPs were found to be significantly associated with CCRT response in the second stage. Single nucleotide polymorphism rs16863886, located between SGPP2 and FARSB on chromosome 2q36.1, was significantly associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.62-10.30) under additive models. Single nucleotide polymorphism rs4954256, located in ZRANB3 on chromosome 2q21.3, was associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.57-10.87). The predictive accuracy for CCRT response was 71.59% with these two SNPs combined. CONCLUSIONS: This is the first study to identify germline polymorphisms with a high accuracy for predicting CCRT response in the treatment of esophageal cancer.

Individuals' leukocyte DNA double-strand break repair as an indicator of radiosurgery responses for cerebral arteriovenous malformations.

To evaluate the feasibility of using radiosensitivity of peripheral leukocytes as a predictor of clinical therapeutic responses to radiosurgery in individuals with cerebral arteriovenous malformation (AVM), we enrolled 18 patients years after they had received Gamma Knife radiosurgery for their cerebral AVM. The AVMs were shown with different degrees of regression in size in posttherapeutic periods. The peripheral leukocytes of these patients were collected at the last neuroimaging follow-ups. The leukocytes, before and 1 and 2 h after 8 Gy external gamma-irradiation, were evaluated for the amounts of DNA double-strand breaks (DSB) in 50 randomly selected individual nuclei by the neutral single cell gel electrophoresis, or so-called comet analysis. After being adjusted for gender and age at radiosurgery, the individuals with less posttherapeutic regression in AMV sizes or relatively poor or inadequate responses to radiosurgery were shown to have significantly higher DSB repair capacity on their leukocytes by comet analysis. These results suggested that in vitro radiosensitivity of peripheral leukocytes may provide valuable information for predicting therapeutic response or for adjusting irradiation doses in AVM radiosurgery.

Age-associated decrease of oxidative repair enzymes, human 8-oxoguanine DNA glycosylases (hOgg1), in human aging.

8-Oxoguanine has been shown to be a dominant cause of oxidative DNA damage by oxygen free radicals in eukaryotic cells. The 8-oxoguanine repair-specific enzyme 8-oxoguanine-DNA glycosylase (hOgg1) was recently cloned and was observed to conduct mainly short-patch base-excision repair. It has also been suggested that reactive oxygen species play an important role in the cellular aging process. We explored the association between the hOgg1 enzyme activity in somatic cells of human subjects of various ages and the role of hOgg1(326) genetic polymorphism. An 8-oxoguanine-containing 28 mer oligonucleotide was end-labeled with gamma-32P ATP and incubated with protein extracts from peripheral blood lymphocytes (PBL) from 78 healthy individuals ranging in age from newborn to 91 years old. The hOgg1 repair activity toward the radiolabelled 8-oxoguanine-containing DNA was determined, and the results indicated a significant age-dependent decrease in the hOgg1 activity in their lymphocytes. Significantly reduced activity was also shown in those with Cysteine/Cysteine genotypes. The genders of the subjects were not shown to be associated. These results provide an important observation regarding the cellular hOgg1 activity in somatic cells during the normal human aging processes.