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Hepatocellular carcinoma (HCC) and secondary liver tumors, such as colorectal cancer liver metastases are significant contributors to the overall burden of cancer‐related morality. Current biomarkers, such as alpha‐fetoprotein (AFP) for HCC, result in too many false negatives, necessitating noninvasive approaches with improved sensitivity. Volatile organic compounds (VOCs) detected in the breath of patients can provide valuable insight into disease processes and can differentiate patients by disease status. Here, we investigate whether 22 VOCs from the breath of 296 patients can distinguish those with no liver disease (n = 54), cirrhosis (n = 30), HCC (n = 112), pulmonary hypertension (n = 49), or colorectal cancer liver metastases (n = 51). This work extends previous studies by evaluating the ability for VOC signatures to differentiate multiple diseases in a large cohort of patients. Pairwise disease comparisons demonstrated that most of the VOCs tested are present in significantly different relative abundances (false discovery rate P

Background Improved detection of hepatocellular carcinoma (HCC) is needed, as current detection methods, such as alpha fetoprotein (AFP) and ultrasound, suffer from poor sensitivity. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate many cellular functions and impact cancer development and progression. Notably, miRNAs are detectable in saliva and have shown potential as non-invasive biomarkers for a number of cancers including breast, oral, and lung cancers. Here, we present, to our knowledge, the first report of salivary miRNAs in HCC and compare these findings to patients with cirrhosis, a high-risk cohort for HCC. Methods We performed small RNA sequencing in 20 patients with HCC and 19 with cirrhosis. Eleven patients with HCC had chronic liver disease, and analyses were performed with these samples combined and stratified by the presence of chronic liver disease. P values were adjusted for multiple comparisons using a false discovery rate (FDR) approach and miRNA with FDR P < 0.05 were considered statistically significant. Differential expression of salivary miRNAs was compared to a previously published report of miRNAs in liver tissue of patients with HCC vs cirrhosis. Support vector machines and leave-one-out cross-validation were performed to determine if salivary miRNAs have predictive potential for detecting HCC. Results A total of 4,565 precursor and mature miRNAs were detected in saliva and 365 were significantly different between those with HCC compared to cirrhosis (FDR P < 0.05). Interestingly, 283 of these miRNAs were significantly downregulated in patients with HCC. Machine-learning identified a combination of 10 miRNAs and covariates that accurately classified patients with HCC (AUC = 0.87). In addition, we identified three miRNAs that were differentially expressed in HCC saliva samples and in a previously published study of miRNAs in HCC tissue compared to cirrhotic liver tissue. Conclusions This study demonstrates, for the first time, that miRNAs relevant to HCC are detectable in saliva, that salivary miRNA signatures show potential to be highly sensitive and specific non-invasive biomarkers of HCC, and that additional studies utilizing larger cohorts are needed.

The degree to which societies differ in dress, diet, laws, and language appears to be such an integral part of today's human experience that some researchers think of it as a hallmark of so-called “modern human behavior.” Yet it remains unclear to what extent the current pattern of relatively low within-region cultural variation paired with relatively high between-region cultural variation can be assessed in time-averaged Paleolithic assemblages. Here, we use a spatially explicit agent-based model to begin to examine how time-averaging can affect the spatial scale of similarity among culturally transmitted variants in archaeological assemblages. Our results show that time-averaging, alone, can increase the scale of local spatial association among the relative frequency of the most prevalent cultural variant in an archaeological landscape. Our findings have important implications for archaeological interpretations of the spatial scale of regional cultural differentiation (or lack thereof) in the Paleolithic record and beyond.