Microbial Biomarkers for Lung Cancer: Current Understandings and Limitations

Abstract

As our “hidden organ”, microbes widely co-exist at various sites on the human body. These microbes are collectively referred to as the microbiome. A considerable number of studies have already proven that the microbiome has significant impacts on human health and disease progression, including cancers. The recent discovery of cancer-specific microbiomes renders these cancer-associated microbes as potential biomarkers and therapeutic targets. While at low biomass levels, the lung microbiome still dramatically influences the initiation, progression and treatment of lung cancers. However, research on lung cancer-associated microbiomes is emerging, and most profiling studies are performed within three years. Unfortunately, there are substantial inconsistencies across these studies. Variations in microbial diversity were observed, and different microbial biomarkers for lung cancer have been proposed. In this review, we summarized the current findings of lung cancer microbiome studies and attempt to explain the potential reasons for the dissimilarities. Other than lung microbiomes, oral and airway microbiomes are highly related to lung microbiomes and are therefore included as well. In addition, several lung cancer-associated bacterial genera have been detected by different independent studies. These bacterial genera may not be perfect biomarkers, but they still serve as promising risk factors for lung cancers and show great prognostic value.

Microbes for lung cancer detection: feasibility and limitations

“…In addition, different experimental studies have yielded different species of dominant microbes in lung cancer patients, but there are some microbes and the effects they produce that have been repeatedly mentioned. These are precisely the focus of our subsequent studies (10). For example, Veillonella is potentially similar to Prevotella in up-regulating the ERK and PI3K signaling pathways to exert oncogenic effects (69).…”

“…However, different studies have shown different dominant genera in lung cancer patients, possibly due to interference from environmental factors, different collection methods and sample sources, and different selections of healthy controls (HC), etc. ( 10 ). We hypothesize whether a method could be devised to accurately control the type of sampling and reduce errors ( 25 ).…”

“…Prevotella is also associated with lung cancer and acts synergistically with Veillonella can directly drive the PI3K/AKT (protein kinase B) and ERK/MAPK (extracellular signal-regulated kinase) signaling pathways, promoting lung cancer development ( 68 , 69 ). Veillonella also promotes lung cancer development by inducing the recruitment of immune cells Th17 and neutrophils and by regulating tribes of microbiota, such as the aggregation of the pro-inflammatory bacterium Pseudomonas aeruginosa ( 10 ). In contrast, the lower respiratory tract is more relevant to the staging and subtyping of lung microbes than the oral and upper respiratory tracts, making it an ideal substitute for lung cancer microbes during collection ( 52 ).…”

Short-chain fatty acids in cancer pathogenesis

“…In addition, bacteria from other anatomical locations (skin, oral cavity, urogenital tract, etc.) may have an impact on cancer risk [ 48 – 51 ]. It is not clear whether probiotics introduced into the gut will have any impact on resident bacteria in these other locations.…”

The Complex Role of the Microbiome in Non-Small Cell Lung Cancer Development and Progression

“…Microorganisms such as bacteria, viruses, and fungi have emerged as pivotal players in the complex interplay of factors contributing to cancer initiation, promotion, and progression [36] and lung cancer development [32,33]. Studies have reported that the levels of Actinomyces, Veillonella, Streptococcus, Megasphaera, and Mycobacterium were more abundant in patients with lung cancer compared with healthy individuals [37][38][39]. Prevotella and Veillonella were most strongly associated with NSCLC, and Veillonella significantly promoted the progression of lung cancer [37].…”