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BackgroundInherited susceptibility and environmental carcinogens are crucial players in lung cancer etiology. The lung microbiome is getting rising attention in carcinogenesis. The present work sought to investigate the microbiome in lung cancer patients affected by familial lung cancer (FLC) and indoor air pollution (IAP); and further, to compare host gene expression patterns with their microbiome for potential links.MethodsTissue sample pairs (cancer and adjacent nonmalignant tissue) were used for 16S rRNA (microbiome) and RNA-seq (host gene expression). Subgroup microbiome diversities and their matched gene expression patterns were analyzed. Significantly enriched taxa were screened out, based on different clinicopathologic characteristics.ResultsOur FLC microbiome seemed to be smaller, low-diversity, and inactive to change; we noted microbiome differences in gender, age, blood type, anatomy site, histology type, TNM stage as well as IAP and smoking conditions. We also found smoking and IAP dramatically decreased specific-OTU biodiversity, especially in normal lung tissue. Intriguingly, enriched microbes were in three categories: opportunistic pathogens, probiotics, and pollutant-detoxication microbes; this third category involved Sphingomonas, Sphingopyxis, etc. which help degrade pollutants, but may also cause epithelial damage and chronic inflammation. RNA-seq highlighted IL17, Ras, MAPK, and Notch pathways, which are associated with carcinogenesis and compromised immune system.ConclusionsThe lung microbiome can play vital roles in carcinogenesis. FLC and IAP subjects were affected by fragile lung epithelium, vulnerable host-microbes equilibrium, and dysregulated immune surveillance and response. Our findings provided useful information to study the triple interplay among environmental carcinogens, population genetic background, and diversified lung microbiome.

Background Both genetic and environmental factors contribute to the development of cancer and its mutant spectrum. Lung cancer has familial aggregation. Lung cancer caused by non-tobacco factors has unique pathological and molecular characteristics. The interaction between genetic lung cancer susceptibility and carcinogens from coal burning remains complex and understudied. Methods We selected 410 non-small cell lung cancer (NSCLC) patients with a family history of lung cancer (FLC) and exposure to coal combustion between 2014 and 2017. Clinicopathologic parameters were analyzed. Reverse transcription-PCR was performed to detect ALK, ROS1, RET, and NTRK1 rearrangement. Results Among the 410 NSCLC patients, 192 had FLC and 204 (49.8%) were exposed to occupational or domestic coal combustion. FLC patients had the same characteristics regardless of gender and coal exposure: younger age, high female ratio, adenocarcinoma, increased metastasis, later stage at diagnosis, and higher frequency of gene fusion. Sixty-seven patients (16.3%) had gene rearrangement: 51 (12.4%) harbored EML4-ALK fusions and 16 ROS1 fusions (3.9%). The highest gene fusion rate (35.1%, 33/94) occurred in patients with both FLC and high tobacco and coal exposure. ALK fusions and total gene rearrangement were closely associated with women, never smokers, younger age, FLC, and coal exposure. Conclusion FLC and exposure to coal combustion have an important impact on the clinicopathological characteristics and gene fusion mode of NSCLC, particularly in cases of higher levels of carcinogens, and genetic susceptibility has a greater impact. Our findings may help evaluate the effect of FLC and coal exposure on the pathogenesis of lung cancer.

The Xuanwei area of Yunnan Province, China, is one of the regions suffering from the highest occurrence and mortality rate of lung cancer in the world. Local residents tend to use bituminous coal as domestic fuel, which causes serious indoor air pollution and is established as the main carcinogen. After the local government carried out furnace and stove reform work, lung cancer rate including incidence and mortality among residents remains high. We herein wonder if there are specific mechanisms at protein level for the development of non‐small‐cell lung cancer (NSCLC) in this area. We investigated the changes of protein profiling in tumour of the patients from Xuanwei area. Tandem mass tag (TMT) was employed to screen the differential proteins between carcinoma and para‐carcinoma tissues. We identified a total of 422 differentially expressed proteins, among which 162 proteins were significantly up‐regulated and 260 were downregulated compared to para‐carcinoma tissues. Many of the differentially expressed proteins were related to extracellular matrix (ECM)‐receptor interaction, focal adhesion, PI3K/AKT pathway and ferroptosis. Further experiments on the two differential proteins, thioredoxin 2 (TXN2) and haptoglobin (HP), showed that the change of their expressions could make the lung cancer cell lines more resistant to erastin or RSL‐induced ferroptosis in vitro, and promote the growth of tumour in nude mice. In conclusion, this study revealed that aberrant regulation of ferroptosis may involve in the development of lung cancer in Xuanwei area.

The chromosomal locations of lncRNAs (long non-coding RNAs, lncRNAs) infer their biological functions in cancer. Lnc-RAB1A-2, a Ras-related protein Rab-1A (RAB1A) upstream lncRNA, was chosen for assessment of its impact on lung cancer prognosis in a case-based analysis and investigation of its biological function though a series of functional assays. Lnc-RAB1A-2 was significantly upregulated in 276 lung cancer tissues compared with corresponding non-tumor tissues, and its expression level was significantly correlated with clinical stage and metastasis status in lung cancer patients. Patients with high expression levels of this lncRNA had a shorter median survival time (16.0 months vs. 23.0 months, P = 0.011 in southern samples; 8.0 months vs. 19.0 months, P = 0.020 in eastern samples; 13.0 months vs. 19.0 months, P = 0.002 in merged samples) and a higher risk of death than those with lower levels (HR = 1.52; 95% CI = 1.01–2.26, in merged samples). Additionally, overexpression of lnc-RAB1A-2 significantly promoted lung cancer cell proliferation in vitro and in vivo. Further analyses using digital gene expression tag profiling revealed that lnc-RAB1A-2 could affect the expression of fibroblast growth factor 1 (FGF1), a gene involved in the PI3K/AKT/mTOR pathway that is largely activated by RAB1A. FGF1 was confirmed to be a down-stream gene of lnc-RAB1A-2. Collectively, our study demonstrated that lnc-RAB1A-2 is associated with poor lung cancer prognosis by promoting lung cancer development.

In this study, we attempted to find out the underlying mechanism of Benzoapyrene and metastasis of lung cancer cells. We also did experiments to testify the connection between BaP and its potential target, TNF-α. Cell median lethal dose (IC50 ) of both cells was measured by crystal violet method. Quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot were employed to detect the expression of TNF-α. Wound healing assay and transwell assay were utilized to testify the impacts of BaP and TNF-α on the metastasis of lung cancer cells. Cell death rate was elevated with the increase of BaP concentration. BaP increased the number of metastatic cells of lung cancer. The expressions of TNF-α pathway-associated protein (TNF-α, NF-kB [P65], Caspase3, and Caspase8) were enhanced by overexpressed BaP. TNF-α shRNA suppressed the positive effects of BaP on migration and invasion of lung cancer cells. Our study validated the positive effects of BaP on the metastasis of lung cancer cells. We also revealed the instrumental role of TNF-α in helping the development of lung cancer cells induced by BaP.

The transcription factor SOX4 has functional importance in foetal lung maturation and tumorigenesis in a number of cancers. However, its biological functions in the progression of lung tumorigenesis remain unclear. In this study, we found that the expression levels of SOX4 mRNA and protein were significantly higher in Xuanwei female lung cancer tissues than in benign lung lesions. The patients with high expression of the SOX4 protein had a higher pathological grade, lymph node (LN) metastasis, poor tumor differentiation and worse prognosis than those patients with low expression of SOX4. Knockdown of the SOX4 gene in the Xuanwei female lung cancer cell line XWLC-05 resulted in apoptotic morphological changes, decreased cell proliferation, invasion and migration. Furthermore, knockdown of the SOX4 gene resulted in obvious sub-G1 peaks and induction of apoptosis through upregulation of caspase-3 expression, while in cells treated with a caspase-3 inhibitor, apoptosis induced by silencing SOX4 expression was inhibited. In vivo analysis in nude mice further confirmed that knockdown of SOX4 suppressed tumor growth. In conclusion, SOX4 appears to be an important tumor suppressor gene in the regulation of Xuanwei female lung cancer cell proliferation, apoptosis and metastases, and it may be a potential target for effective lung cancer therapy. J. Cell. Biochem. 116: 1007–1018, 2015. © 2015 Wiley Periodicals, Inc.

Xuanwei district in Yunnan Province of China has pretty high incidence of lung cancer in China, even a- round the world. Studies have shown that there exists a close relationship between lung cancer and local indoor air pollution caused by Bituminous coal. Considering that the indoor air pollution in Xuanwei District is caused by "open fireplace", an indoor air pollution simulation system was designed, and an F344 rats lung damage model was estab- lished for this indoor air pollution fireplace. The model is based on indoor air pollution simulation system with signal multiplexer control and multi-channel acquisition, and mining PID algorithm was used for polynomial fitting to each test point, and a relatively constant PM2. 5 air pollution status was simulated. The results showed that the system could simulate a variety of states of air pollution, provide a new test method for evaluation of human injury caused by indoor air pollution and a new idea for the study of the incidence of lung cancer in Xuanwei district and other places.

The mismatch between pleural space and remnant lung after bilobectomy has been considered as the main reason for the high incidence of postoperative complications in non-small cell lung cancer (NSCLC) patients. The aim of this study is to analyze the differences in postoperative complications between bilobectomy and lobectomy in the right lung of NSCLC patients.This study included 528 NSCLC patients who underwent right pulmonary lobectomy. A total of 352 cases that underwent upper or lower right lobectomy (108 upper and 244 lower) were the control group, and 176 cases that underwent bilobectomy (57 upper and middle and 119 lower and middle) were the observation group. A retrospective case-control study was performed on a series of matched NSCLC patients. Cases and controls were matched by age, ppoFEV1%, LEVF%, operation method, cardiac comorbidity, type of postoperative management, and pathological type at a ratio of 1:2. The prevalence of 30-day death, occurrence of cardiac-respiratory complications (hospital-acquired pneumonia, low oxygen concentration, pulmonary embolism, cerebral apoplexy, arrhythmia, myocardial ischemia or infarction, and cardiac insufficiency) and occurrence of space-related complications (atelectasis, air leak more than 5 days, and pneumothorax) were compared between the bilobectomy and lobectomy groups.The prevalence of 30-day death was 3.4% (6/176) in the bilobectomy group and 2.3% (8/352) in the lobectomy group. No statistical significance was observed between the two groups. The cardiac-respiratory complication rate in bilobectomy group (23.8%; 42/176) was higher than that in lobectomy group (10.7%; 38/352). The cardiac-respiratory complication rate of the lower and middle pulmonary lobectomy patients in the bilobectomy group (26.5%; 31/119) was significantly higher than that in the lower pulmonary lobectomy patients (4.9%; 12/244). The space-related complications in bilobectomy group and lobectomy group were 20.4% (36/176) and 17.3% (61/352), respectively. No statistically significant difference between the two groups was observed.The postoperative cardiac-respiratory complications of NSCLC patients with right bilobectomy are higher than those of the right lobectomy patients, but the prevalence of 30-day death and space-related complication was not statistically different between the two groups.背景与目的 双肺叶切除后剩余肺叶与胸膜腔空间不匹配是右侧非小细胞肺癌（non-small cell lung cancer, NSCLC）患者术后高并发症发病率的主要原因。本研究旨在比较右侧NSCLC双肺叶切除与单肺叶切除患者术后并发症发生率之间的差异。方法 本研究共纳入行右侧肺叶切除NSCLC 528例，右肺单肺叶切除病例352例（108例上叶与244例下叶）为对照组，右肺双肺叶切除病例176例（57例中上叶与119例中下叶）为观察组。两组病例行回顾性病例-对照配对研究。两组病例按照年龄、性别、术前预计FEV1%、LEVF%、手术方式、术前心脏伴随疾病、术后管理方式、病理类型、肿瘤大小等情况进行按1:2进行配对。比较两组患者术后30天内死亡率、空间相关并发症（肺不张、漏气大于5天、气胸）发生率与心肺并发症（院内获得性肺炎、低氧气血症、肺栓塞、脑卒中、心律失常、心肌缺血或梗塞、心功能不全）发生率之间的差异。结果 双肺叶切除组病例术后30天死亡率为3.4%（6/176），单肺叶切除组病例为2.3 %（8/352），两者间差异无统计学意义；双肺叶切除组病例术后心肺并发症总体发病率为23.8%（42/176）高于单肺叶切除组10.7%（38/352），差异具有统计学意义；双肺叶切除组中下叶切除病例的心肺并发症发病率为26.5%（31/119）远高于单肺叶切除组4.9%（12/244）；而空间相关并发症双肺叶切除组与单肺叶切除组分别为20.4%（36/176）和17.3%（61/352），两者间差异无统计学意义。结论 右侧NSCLC双肺叶切除患者术后心肺相关并发症发生率高于单肺叶切除患者， 30天内死亡率与空间相关并发症发生率无明显差异。