Objective: Xeroderma Pigmentosum Complementation Group C (XPC) is a protein involving in nucleotide excision repair (NER). XPC also plays an important role in the lung cancer occurrence with the mechanism remian unclear up to date. Studies showed that the increased stemness of lung cancer cells is related to the recurrence and metastasis of lung cancer. This study aimed to study and analyze the correlation of XPC with lung cancer stem cell biomarkers expression and the overall survival (OS) of lung adenocarcinoma patients. Methods: 140 cases of clinical lung adenocarcinoma tissue samples and 48 cases of paired paracancerous tissue samples were made into tissue microarray. Immunohistochemistry (IHC) was used to detect the expression of XPC and CD133 in cancer and paracancerous tissues. Semi-quantitative analysis and statistics were performed by Pannoramic Digital Slide Scanner. The expression of XPC and CD133 in fresh tissues was verified by Western blotting assay. siXPC was used to knock down XPC in lung cancer cell lines to study the effect of XPC on the expression of lung cancer stem cell biomarkers and the ability of cell invasion. And shXPC was used to knockdown XPC in A549 and H1650 to study the effect of XPC on the expression of lung cancer stem cell biomarkers. Results: IHC and Western blotting results showed that XPC expression significantly decreased, while CD133 expression significantly increased in cancer tissues comparing to paracancerous tissues (P XPC < 0.0001, P CD133 = 0.0395). The high level of XPC in cancer was associated with a better prognosis (Log-rank p = 0.0577) in lung adenocarcinoma patients. Downregulation of XPC in lung cancer cells showed increased expression of cancer stem cell biomarkers and the increased cell invasion abilities. Conclusion: It is suggested that XPC can exert the ability of anti-tumor formation, tumor invasion and metastasis inhibition, and prognostic survival improvement in lung adenocarcinoma patients by regulating the stemness of lung cancer cells.

Although the Food and Drug Administration has authorized the marketing of "heat-not-burn" (HnB) electronic cigarettes as a modified risk tobacco product (MRTP), toxicological effects of HnB smoke exposure on the brain are still unexplored. Here, paramagnetic resonance of the prefrontal cortex (PFC) of HnB-exposed rats shows a dramatic increase in reactive radical species (RRS) yield coupled with an inflammatory response mediated by NF-κB-target genes including TNF-α, IL-1β, and IL-6 and the downregulation of peroxisome proliferator-activated receptor (PPAR) alpha and gamma expression. The PFC shows higher levels of 8-hydroxyguanosine, a marker of DNA oxidative damage, along with the activation of antioxidant machinery and DNA repair systems, including xeroderma pigmentosum group C (XPC) protein complex and 8-oxoguanine DNA glycosylase 1. HnB also induces the expression of drug-metabolizing enzymes such as CYP1A1, CYP2A6, CYP2B6, and CYP2E, particularly involved in the biotransformation of nicotine and several carcinogenic agents such as aldehydes and polycyclic aromatic hydrocarbons here recorded in the HnB stick smoke. Taken together, these effects, from disruption of redox homeostasis, inflammation, PPAR manipulation along with enhanced bioactivation of neurotoxicants, and upregulation of cMYC protooncogene to impairment of primary cellular defense mechanisms, suggest a possible increased risk of brain cancer. Although the HnB device reduces the emission of tobacco toxicants, our findings indicate that its consumption may carry a risk of potential adverse health effects, especially in non-smokers so far. Further studies are needed to fully understand the long-term effects of these devices.