Although the morbidity of multiple primary lung cancer (MPLC) has been increasing year by year, it is still controversial about pathogenesis, differential diagnosis and management strategies of MPLC. hTis review provides a snap-shot of the main progress of pathogenesis, differential diagnosis and management strategies of MPLC.

Background and objective Synchronous multiple primary lung cancer (sMPLC) is a sparse disease in the past, but there has been a gradual increase in the morbidity of sMPLC recently. However, studies on large sample have never been undertaken. hTe purpose of this study is to investigate the diagnosis, treatment and prognosis of sMPLC through analyzing the clinical data, and provide supports for the management of sMPLC. Methods According to Martini-Melamed criteria, 357 patients were diagnosed sMPLC. hTe pathological staging is on the basis of the 8th edition tumor-node-metastasis (TNM) staging from International Association for the Study of Lung Cancer (IASLC). Results There were 269 patients with double primary lung cancer, 65 patients with triple primary lung cancer and 23 patients with four or more primary lung cancer. Lesions (68.55%, 571/833) were frequently in upper lobe, especially the right upper lobe. Adenocarcinoma (95.56%, 796/833) was the mainly pathological type, followed by squamous cell carcinoma (2.40%, 20/833). hTe acinar predominant subtype was the main part (70.81%, 313/442) of the all adenocarcinoma specimens. Most of the lesions (68.35%, 244/357) were stage Ib or low. Among the initial lesion and the following lesions ,patients who had the same pathological type (92.72%, 331/357) were more than the different (7.28%, 26/357), of which adenocarcinoma-adenocarcinoma occupied the major pro-portion (99.40%, 329/331). hTe 3-year overall survival (OS) and 5-year overall survival were respective 91.93%and 84.37%. Multivariate analysis found that smoking history (P=0.012), the diameter of the maximum lesion (P=0.027), lymph node me-tastasis (P=0.015) and pleural invasion (P<0.001) were the independent risk factors for prognosis. Conclusion Tumours in patients with sMPLC are more frequently in the right upper lobe. Adenocarcinoma was the mainly pathological type. Smoking history, the diameter of the maximum lesion, lymph node metastasis and pleural invasion were the independent risk factors for prognosis. Early diagnosis and active operation can obtain better prognosis.

Lipid-formulated RNA vaccines have been widely used for disease prevention and treatment, yet their mechanism of action and individual components contributing to such actions remain to be delineated. Here, we show that a therapeutic cancer vaccine composed of a protamine/mRNA core and a lipid shell is highly potent in promoting cytotoxic CD8⁺ T cell responses and mediating anti-tumor immunity. Mechanistically, both the mRNA core and lipid shell are needed to fully stimulate the expression of type I interferons and inflammatory cytokines in dendritic cells. Stimulation of interferon-β expression is exclusively dependent on STING, and antitumor activity from the mRNA vaccine is significantly compromised in mice with a defective Sting gene. Thus, the mRNA vaccine elicits STING-dependent antitumor immunity.

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
Adenocarcinoma of Lung/genetics* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Carcinoma, Squamous Cell/genetics* ; Genetic Heterogeneity ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Lung Neoplasms/genetics* ; Polymorphism, Single Nucleotide