BackgroundImmune checkpoint inhibitors have achieved breakthrough efficacy in treating lung adenocarcinoma (LUAD) with wild-type epidermal growth factor receptor (EGFR), leading to the revision of the treatment guidelines. However, most patients with EGFR mutation are resistant to immunotherapy. It is particularly important to study the differences in tumor microenvironment (TME) between patients with and without EGFR mutation. However, relevant research has not been reported. Our previous study showed that secreted phosphoprotein 1 (SPP1) promotes macrophage M2 polarization and PD-L1 expression in LUAD, which may influence response to immunotherapy. Here, we assessed the role of SPP1 in different populations and its effects on the TME.MethodsWe compared the expression of SPP1 in LUAD tumor and normal tissues, and in samples with wild-type and mutant EGFR. We also evaluated the influence of SPP1 on survival. The LUAD data sets were downloaded from TCGA and CPTAC databases. Clinicopathologic characteristics associated with overall survival in TCGA were assessed using Cox regression analysis. GSEA revealed that several fundamental signaling pathways were enriched in the high SPP1 expression group. We applied CIBERSORT and xCell to calculate the proportion and abundance of tumor-infiltrating immune cells (TICs) in LUAD, and compared the differences in patients with high or low SPP1 expression and wild-type or mutant EGFR. In addition, we explored the correlation between SPP1 and CD276 for different groups.ResultsSPP1 expression was higher in LUAD tumor tissues and in people with EGFR mutation. High SPP1 expression was associated with poor prognosis. Univariate and multivariate cox analysis revealed that up-regulated SPP1 expression was independent indicator of poor prognosis. GSEA showed that the SPP1 high expression group was mainly enriched in immunosuppressed pathways. In the SPP1 high expression group, the infiltration of CD8+ T cells was lower and M2-type macrophages was higher. These results were also observed in patients with EGFR mutation. Furthermore, we found that the SPP1 expression was positively correlated with CD276, especially in patients with EGFR mutation.ConclusionSPP1 levels might be a useful marker of immunosuppression in patients with EGFR mutation, and could offer insight for therapeutics.

Growing incidence of lung adenocarcinoma (LUAD) has been detected recently. Multiple long non-coding RNAs (lncRNAs) have been proven as tumor facilitators or inhibitors by extensive works. Present study concentrated on characterizing the potential role of LINC01123 in LUAD. We explored the differential expression of LINC01123 through qRT-PCR and found the amplification of LINC01123 in LUAD cell lines. It was ascertained that LINC01123 was definitely responsible for the malignant processes of LUAD cells. Further, we validated the ceRNA network of LINC01123/miR-449b-5p/NOTCH1 in LUAD via mechanical experiments. As a transcriptional factor related to epithelial mesenchymal transition (EMT), ZEB1 was responsible for the transcriptional activation of both LINC01123 and NOTCH1. The involvement of NOTCH signaling in LUAD was interrogated through evaluating functional changes after treating with FLI-06 (NOTCH pathway suppressor). It showed that FLI-06-caused NOTCH signaling inactivation suppressed malignant functions in LUAD cells. Additionally, LINC01123 facilitated NOTCH1-dependent NOTCH signaling activation. Rescue experiments probed the modulatory function of LINC01123/miR-449b-5p/NOTCH1 in LUAD cellular processes. Altogether, ZEB1-activated LINC01123 accelerates the malignancy in LUAD through miR-449b-5p/NOTCH1 axis-mediated NOTCH signaling pathway, while NOTCH1 boosts ZEB1 in return. These observations suggest the huge potential of LINC01123 as a new target for LUAD therapy.

Background. It has been known that there are microecology disorders during lung cancer development. Theoretically, intratumoral microbiota (ITM) can impact the lung cancer (LC) survival and treatment efficacy. This study conducted a follow-up investigation of non-small cell lung cancer (NSCLC) patients without lung infection to prove whether ITM indeed impacts the first-line treatment efficacy and survival. Methods. We enrolled all patients diagnosed with NSCLC in our department from 2017 to 2019, whose tumor samples were available (through surgery or biopsy) and sent for pathogen-targeted sequencing. All patients received the first-line treatment according to the individual situation. In the short term, the efficacy of the first-line treatment was recorded. During the follow-up, the survival status, progress events, and overall survival (OS) period were recorded if a patient was contacted. Results. Firstly, 53 patients were included, and our following analysis focused on the stage III and stage IV cases with ADC, SCC, or ASC tumors (47 cases). Several bacteria are associated with the LC status and progression, including N stages, metastasis sites, epidermal growth factor receptor (EGFR) mutation, first-line outcome, and later survival. The risk bacteria include Serratia marcescens, Actinomyces neesii, Enterobacter cloacae, and Haemophilus parainfluenzae; and the protective (against LC development and progression) ones include Staphylococcus haemolyticus and Streptococcus crista. In the logistic regression, the two-year survival can be predicted using the results of four bacteria (Haemophilus parainfluenzae, Serratia marcescens, Acinetobacter jungii, and Streptococcus constellation), with an accuracy rate of 90.7%. Conclusion. ITM have links to malignancy, EGFR mutation, first-line outcome, and survival of NSCLC. Our results implied the potential anti-NSCLC activity of antibiotics when used reasonably. It is still necessary to deepen the understanding of the characteristics of ITM and its interactions with NSCLC tumors and the immune cells, which is significant in individualized approaches to the LC treatment.

Background The microbial community affects the occurrence, development, metastasis and treatment response of cancers. But the detailed role and characteristics of lung microbiota (LM) in non-small cell lung cancer (NSCLC) are not fully known. For NSCLC associated microbiota analysis, it is valuable to combine multiple levels of detection, e.g., tumor, blood plasma, and bronchoalveolar fluid (BALF), but not single tissues. Methods This study collected above three sample types from NSCLC patients free from lung infection and aimed to describe their LM features using sequencing techniques. All patients diagnosed at the Department of Oncology in Shijiazhuang People’s Hospital with stage III or IV NSCLC from May 2019 to April 2020 were enrolled. All 37 pieces of tumor tissues and 6 blood samples were sent for pathogen targeted sequencing; for the BALF samples, 4 were used for pathogen targeted sequencing and 2 were sent for 16S ribosomal DNA (rDNA) sequencing. Results We detected 49 pathogenic microorganisms (PMs) in the 37 tumor samples, 28 PMs in the 4 BALF samples, and 14 PMs in the 6 plasma samples. Overall, there were 5 common PMs in 3 types of samples. Between the tumor and BALF samples, there were another 11 common elements. In the 5 tumor-plasma pairs, the presence of a specific PM in blood was not necessarily consistent with that in the tumor. In the tumor-BALF pairs, the PM diversity was dramatically higher in the BALF than in the tumor. The PMs detected in the BALF could largely cover the PMs in the tumor. In the BALF 16S rDNA sequencing, there were 82 common operational taxonomic units (OTUs), and the microbiota in the BALF of advanced NSCLC patients exhibited some similarity. Conclusions This study showed the unique features of LM. The amount of intra-tumoral PMs was not necessarily consistent with that in the blood, but there was an obvious correlation between the intra-tumoral microbiota and that in the BALF. It is convenient and non-invasive to obtain BALF. Detection of LM classification and abundance in the BALF may help evaluate the severity of NSCLC.

Background: To evaluate the clinical efficacy of arthroscopic therapy with infrapatellar fat pad cell concentrates in treating knee cartilage lesions, we conducted a prospective randomized single-blind clinical study of controlled method.Methods: 60 cases from Shanghai Changzheng Hospital during April 2018 to December 2019 were chosen and randomly divided into 2 groups equally. Patients in the experiment group were treated through knee arthroscopy with knee infrapatellar fat pad cell concentrates containing mesenchymal stromal cells, while patients in the control group were treated through regular knee arthroscopic therapy. VAS and WOMAC scores were assessed at pre-operation, and 6-weeks, 12-weeks, 6-months, and 12-months after intervention. MORCART scores were assessed at pre-operation and 12-months after intervention.Results: 29 cases in the experiment group and 28 cases in the control group were followed up. No significant difference in VAS, WOMAC, and MOCART scores were found between the two groups before surgery (P>0.05). The WOMAC-Total and WOMAC-Function scores of experiment group were significantly lower than those of control group 6 months, 12 months after surgery (P<0.05). The VAS-Rest and VAS-Motion scores of experiment group were found significantly lower than those of control group 12 months after surgery (P<0.05). The MOCART scores of experiment group were found significant higher compared with control group 12 months after surgery (P<0.05). No significant difference in WOMAC-Stiffness scores were found between the two groups. Conclusions: The short-term results of our study are encouraging and demonstrate that knee arthroscopy with infrapatellar fat pad cell concentrates containing mesenchymal stromal cells is safe, and provides assistance in reducing pain and improving function in patients with knee cartilage lesions.