Circulating tumor cells in patients with lung cancer: developments and applications for precision medicine.

Lung cancer is the most common cause of cancer-related deaths, with most patients dying with distant metastases. Circulating tumor cells (CTCs) are cancer cells that have disseminated into the peripheral blood from primary or metastatic sites and present great potentials as prognostic biomarkers for guiding individualized treatment in lung cancer. To date, various methods have been developed to capture CTCs in peripheral blood, and some approaches for the detection of CTC in lung cancer have shown both high sensitivity and specificity. The CTC analyses offer much promise as a real-time 'liquid biopsy' for prognosis evaluation and therapy intervention in lung cancer. In this Review, we present and discuss the current status of CTC detection and applications in lung cancer.

Asymmetric Total Synthesis of Lancifodilactone G Acetate. 1. Diastereoselective Synthesis of CDEFGH Ring System.

The stereoselective construction of the CDEFGH ring system of lancifodilactone G is described. The key steps in this synthesis are (i) ring-closing metathesis for formation of the oxa-bridged eight-membered ring; (ii) an intramolecular Pauson-Khand reaction for construction of the sterically congested F ring; and (iii) sequential cross-metathesis, hydrogenation, and lactonization reactions for installation of the anomerically stabilized bis-spiro ketal fragment of lancifodilactone G.

CD47 is a novel potent immunotherapy target in human malignancies: current studies and future promises.

Recently, many immunosuppressive checkpoints such as PD-L1, CTLA-4 and CD47, were identified in succession and serve as potential immunotherapy targets in human cancers. Among them, CD47, a 'marker-of-self' protein that is overexpressed broadly across tumor types, is emerging as a novel potent macrophage immune checkpoint for cancer immunotherapy. In this review, we highlight the prominent role of CD47 as a 'don't-eat-me' signal that inhibits macrophage phagocytosis for immune evasion of a tumor and presents the opportunities and challenges for CD47 inhibitors both as monotherapy and in combination treatments for hematological cancers and solid tumors; some of these agents are currently in clinical trials.

[The value of bronchoscopy in the diagnosis of sarcoidosis].

OBJECTIVE: To evaluate the role of bronchoscopy in the diagnosis of sarcoidosis. METHODS: A retrospective analysis was conducted for 200 patients who were diagnosed to have sarcoidosis and underwent bronchoscopy from June 2009 to June 2014 in Peking Union Medical College Hospital. The diagnostic value of different bronchoscopic procedures was analyzed. RESULTS: Of the 200 patients, 145 were finally confirmed to have sarcoidosis by pathology through bronchoscopic sampling techniques. The diagnostic yields of endobronchial biopsy (EBB), transbronchial lung biopsy (TBLB), and EBUS-TBNA were 71.14%, 46.77%, 46.80%, respectively. The yields among the 3 techniques were statistically different. In those with mucosal lesions, the yield of EBB was 80.80%, while that of the combination of EBB, TBLB and EBUS-TBNA was 83.3%, the difference being not significant. In those without mucosal lesions, the yields of EBB, and the combination of EBB, TBLB and EBUS-TBNA were 20.8% and 48.0% respectively, with significant difference(χ(2)=4.463, P=0.035). CONCLUSIONS: EBB is a preferred approach for the diagnosis of sarcoidosis with endobronchial abnormalities, while for cases without mucosal lesions, combined TBLB, EBUS-TBNA and bronchoalveolar lavage can improve the diagnostic yield.

Melatonin potentiates the antiproliferative and pro-apoptotic effects of ursolic acid in colon cancer cells by modulating multiple signaling pathways.

Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, is largely distributed in medical herbs and edible plants. Melatonin is an indoleamine compound produced in the pineal gland and also a plant-derived product. Both UA and melatonin have been shown to inhibit cancer cell growth in numerous studies, but they have never been combined altogether as an anticolon cancer treatment. In this study, we investigated whether the association between UA and melatonin leads to an enhanced antiproliferative and pro-apoptotic activities in colon cancer SW480 and LoVo cells. We found that combined treatment with UA and melatonin significantly enhanced inhibition of cell viability and migration, promoted changes in cell morphology and spreading, and increased induction of apoptosis, thereby potentiating the effects of UA alone in colon cancer cells. Moreover, we found that the enhanced effects of UA and melatonin combination are mediated through simultaneous modulation of cytochrome c/caspase, MMP9/COX-2, and p300/NF-κB signaling pathways. Combined treatment with UA and melatonin triggered the release of cytochrome c from the mitochondrial intermembrane space into the cytosol, induced cleavage of caspase and PARP proteins, enhanced inhibition of MMP9 and COX-2 expression, promoted p300 and NF-κB translocation from cell nuclei to cytoplasm, and abrogated NF-κB binding and p300 recruitment to COX-2 promoter in colon cancer cells. These results, therefore, demonstrated that melatonin potentiated the antiproliferative and pro-apoptotic effects of UA in colon cancer cells by modulating multiple signaling pathways and suggest that such a combinational treatment might potentially become an effective way in colon cancer therapy.

Mammary mucinous cystadenocarcinoma with long-term follow-up: molecular information and literature review.

BACKGROUND: Mucinous cystadenocarcinoma (MCA) is a very rare form of breast cancer that was first described in 1998. Only 33 cases of primary MCA, including our present case, have been reported thus far. As a consequence, its molecular features, prognosis and treatment regimen are poorly known. Here, we describe a less common presentation of MCA, detail its molecular features, discuss the major differential diagnosis, and provide a brief review of the literature. CASE PRESENTATION: A 59-year-old woman presented with a breast lump in which mammography showed a well-defined nodule. Core needle biopsy (CNB) revealed several lesions lined by tall columnar cells with stratification and abundant mucinous secretion; excision was recommended for final diagnosis. The resected specimens showed cavities of different sizes without surrounding myoepithelial cells. The cavities were rich in mucus, and the nuclei were located at the base of the cells, containing intracellular mucus. Immunohistochemical analysis revealed that it was triple-negative breast cancer (TNBC). Next-generation sequencing (NGS) revealed pathogenic mutations in the PIK3CA, KRAS, MAP2K4, RB1, KDR, PKHD1, TERT, and TP53 genes. A diagnosis of MCA was rendered. The patient has been followed up for 108 months to date and showed no signs of recurrence or metastasis. CONCLUSION: Our study presents the gene profile of an MCA case with no recurrence or metastatic tendency after 108 months of follow-up, and a review of the literature helps us better understand the clinical, pathologic, and molecular features of this tumor.

Circulating tumor cells PD-L1 expression detection and correlation of therapeutic efficacy of immune checkpoint inhibition in advanced non-small-cell lung cancer.

INTRODUCTION: This study investigated whether programmed death-ligand 1 (PD-L1) expression of circulating tumor cells (CTCs) in peripheral blood can serve as a predictive biomarker for immunotherapy efficacy in patients with advanced non-small-cell lung cancer (NSCLC). METHODS: We employed a negative enrichment method to isolate CTCs. We identified PD-L1 + CTCs as PD-L1+/4',6-diamidino-2-phenylindole (DAPI)+/CD45-circulating tumor cells through an immunofluorescence method. Tumor tissue PD-L1 expression was determined by immunohistochemical staining. The correlation between CTC PD-L1 expression and patients' prognostic features was estimated through the Kaplan-Meier method. RESULTS: CTCs released a higher detection rate of PD-L1 expression than tumor tissues (53.0% vs. 42.1%). No correlation was observed between them. Forty-nine NSCLC patients received anti-PD-1/PD-L1 immunotherapy (three with combined anti-PD-1/PD-L1 and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), two with four cycles of combined immune checkpoint inhibitors [ICIs] plus chemotherapy and ICI monotherapy for maintenance). Patients with PD-L1 expression on tissue or CTCs had a median progression-free survival (mPFS) of 5.6 months (n = 36, 95% confidence interval [CI] 3.6-7.5 months), significantly longer than those without PD-L1 detection (n = 9, mPFS of 1.4 months, 95% CI 1.3-1.5 months, log-rank p = 0.032). The multivariable Cox proportional-hazard model suggested that the tissue or CTC PD-L1 expression was associated with a lower risk of progression (hazard ratio 0.45, 95% CI 0.21-0.98, p = 0.043). CONCLUSIONS: CTCs and tumor tissues reveal heterogeneous expression of PD-L1 in NSCLC patients. Patients with baseline PD-L1 expression on CTCs or tissue showed prolonged mPFS and may help to identify the subsets of patients who potentially benefit from immunotherapy.

Effects of soil moisture, net radiation, and atmospheric vapor pressure deficit on surface evaporation fraction at a semi-arid grass site.

Surface energy partitioning is one of the most important aspects of the land-atmosphere coupling. The objective of this study is to examine how soil moisture (SM) and atmospheric conditions (net radiation, Rn and vapor pressure deficit, VPD) affect surface evaporation fraction (EF, determined by LE/(LE + H), where LE and H are latent and sensible heat flux, respectively) with measurements at a semi-arid grass site in China during the mid-growing season, 2020. The three factors (SM, Rn, and VPD) were divided into different levels, and then their effects on EF were investigated qualitatively using a combinatorial stratification method and quantificationally using a path analysis. Generally, the results indicated that the effect of one factor of SM, Rn and VPD on EF was influenced by the other two factors. EF tended to increase with increasing SM. Increased VPD (Rn) enhanced (weakened) the SM-EF relationship. When soil was dry, EF tended to decrease with increasing VPD; when soil was wet, EF initially levelled off and then decreased with increasing VPD. Increased Rn enhanced (weakened) the positive (negative) effect of VPD on EF when soil was wet (dry). In terms of Rn effect, EF tended to decrease as Rn increases. Further, path analysis suggested that SM, Rn, and VPD not only directly affected EF, but also indirectly affected EF, mainly through canopy conductance (Gs) and temperature difference between land surface and air (∆T). The direct effect of SM accounted for >50 % of its total effect on EF, while the total effects of Rn and VPD on EF were dominated by their indirect effects. These observational evidences may have implications for improving representation of land-atmosphere coupling in atmospheric general circulation models over the semi-arid regions covered by grass.

Mitigation of postoperative urinary retention among total joint replacement patients using the ERAS protocol and applying risk-stratified catheterization.

BACKGROUNDS: We intended to identify the incidence and risk factors (RFs) for Postoperative urinary retention (POUR) after applying a risk-stratified catheterization optimization method in enhanced recovery after surgery (ERAS)-total joint arthroplasty (TJA). METHODS: A total of 381 patients were prospectively monitored for POUR. POUR diagnosis was done by a perioperative specialist. Data on potential risk factors (RFs) for POUR were accumulated. Univariate analysis (UA) was conducted to identify possible indicators of POUR, followed by multivariate analysis (MA) of identified indicators. RESULTS: POUR occurred in 5.5% of cases, including 8 (3.4%) patients underwent total knee arthroplasty and 13 (10.4%) patients underwent total hip arthroplasty. In UA, age, sex, American Society of Anesthesiologists (ASA) score, and the type of operation were significantly different on UA (P = 0.046, P = 0.022, P = 0.000 and P = 0.049, respectively). Other additional predictors, including body mass index (BMI), international prostate symptom score (IPSS) score, preoperative haemoglobin (Hb), duration of operation, estimated intraoperative blood loss, intraoperative fluid volume, fluid infusion volume within 24 h postoperatively were not associated with POUR (P > 0.05). MA results demonstrated that age, ASA score, type of operation and standard intraoperative placement of an indwelling bladder catheter (SIP-IBC) were strongly associated with POUR development risk (P < 0.05). CONCLUSION: Overall, we had a low POUR incidence in our study cohort. However, with the shift from non-ERAS TJA to ERAS TJA protocol, it is crucial to closely monitor the male gender, advanced age, THA and SIP-IBC, as these variables can markedly enhance POUR risk.

A PDZ Protein GIPC3 Positively Modulates Hedgehog Signaling and Melanoma Growth.

The hedgehog (Hh) pathway is essential for animal development, but aberrant activation promotes cancer growth. In this study, we show that GIPC3, a PDZ domain-containing protein with putative adaptor protein function, positively modulates Hh target gene expression in normal fibroblasts and melanoma cells and supports melanoma tumor growth. Using overexpression and epistasis studies, we show that Gipc3 potentiates Hh transcriptional output and that it modulates GLI-dependent transcription independently of Sufu. Whereas we find that GIPC3 protein does not interact with Hh pathway components, Ingenuity Pathway Analyses of GIPC3-interacting proteins identified by coimmunoprecipitation and mass spectrometry show an association with cancer pathogenesis. Subsequent interrogation of The Cancer Genome Atlas and the Human Protein Atlas databases reveals GIPC3 upregulation in many cancers. Using expression screens in selected groups of GIPC3-upregulated cancers with reported Hh pathway activation, we find a significant positive correlation of GIPC3 expression with Hh pathway components GLI1, GLI2, and GPR161 in melanoma lines. Consistently, GIPC3 knockdown in melanoma lines significantly reduces GLI1 and GLI2 expression, cell viability, colony formation, and allograft tumor growth. Our findings highlight previously unidentified roles of GIPC3 in potentiating Hh response and melanoma tumorigenesis and suggest that GIPC3 modulation on Hh signaling may be targeted to reduce melanoma growth.

Simulated atmospheric nitrogen deposition inhibited the leaf litter decomposition of Cinnamomum migao H. W. Li in Southwest China.

Atmospheric nitrogen (N) deposition could affect various ecological processes in forest ecosystems, including plant litter decomposition and nutrient cycling. However, the mechanism of underlying litter decomposition and nutrient cycling of Cinnamomum migao under N deposition remains unclear. Therefore, we conducted a simulated N deposition experiment including four onsite treatments to assess the effects of N input on C. migao leaf litter decomposition, nutrient release, and soil enzyme activity. The results showed that simulated N deposition significantly increased the amount of total residual mass and lignin and cellulose, decreased the decomposition rate, and suppressed net nutrient release. N input increased C, N, and P ratios as decomposition progressed, and the proportion of mass remaining was positively correlated with the proportions of lignin and cellulose remaining at the later stage of decomposition. The differences in soil enzyme activity were primarily due to enzyme type and sampling time. We conclude that simulated N deposition significantly suppressed the leaf litter decomposition of C. migao by mainly altering the chemical properties and suppressing the decomposition of the organic matter in leaf litter. Lignin might have played an important role in the loss of leaf litter biomass at the later stage of decomposition.

SREBP1 site 1 protease inhibitor PF-429242 suppresses renal cell carcinoma cell growth.

Renal cell carcinoma (RCC) cells have increased lipogenesis and cholesterol synthesis. Sterol regulatory element-binding protein-1 (SREBP1) is cleaved by site 1 protease (S1P) to release the transcriptionally active amino-terminal domain. PF-429242 is a potent and competitive S1P inhibitor. We here tested its activity in RCC cells. In established and primary human RCC cells, PF-429242 potently inhibited cell proliferation, migration, and invasion. The S1P inhibitor provoked apoptosis activation in RCC cells. Furthermore, shRNA-mediated S1P silencing or CRISPR/Cas9-induced S1P knockout led to RCC cell growth inhibition and apoptosis activation. Conversely, ectopic overexpression of SREBP1 or S1P augmented RCC cell proliferation and migration. Daily i.v. injection of a single dose of PF-429242 robustly inhibited RCC xenograft growth in severe combined immunodeficiency mice. Additionally, intratumoral injection of S1P shRNA lentivirus inhibited RCC xenograft growth in mice. SREBP1, S1P, and its target gene low density lipoprotein receptor (LDLR) were significantly elevated in human RCC tissues. These results suggest that targeting S1P by PF-429242 inhibited RCC cell growth in vitro and in vivo.

Ikaros is heterogeneously expressed in lung adenocarcinoma and is involved in its progression.

OBJECTIVE: The aim of the present study was to assess the expression of the Ikaros transcription factor (IKZF1) in lung adenocarcinoma and investigate whether expression levels of Ikaros are correlated with lung adenocarcinoma progression. METHODS: We conducted a retrospective study of 325 cases of resected stage I pulmonary adenocarcinoma, in which histological subtyping was performed according to the 2015 World Health Organization classification. We performed immunohistochemical examinations to assess expression of Ikaros in pulmonary adenocarcinomas and evaluated the correlation between Ikaros expression and cancer progression. RESULTS: Immunohistochemical staining was heterogeneous, with the majority of well-differentiated and moderately differentiated lung adenocarcinomas being weakly positive and the majority of the poorly differentiated lung adenocarcinomas exhibiting strong positive staining. Higher expression of Ikaros was associated with tumor recurrence or metastasis. CONCLUSIONS: Ikaros is heterogeneously expressed in different subtypes of lung adenocarcinoma; higher expression of Ikaros was found to be associated with cancer progression.

Positive tumour CD47 expression is an independent prognostic factor for recurrence in resected non-small cell lung cancer.

BACKGROUND: Immunotherapy is a promising advance in oncology. Limited information exists regarding the interrelationship between CD47 expression and tumour-associated macrophage-related immuno-microenvironment in patients with non-small cell lung cancer (NSCLC). These factors may predict novel immunotherapy efficacy. PATIENTS AND METHODS: CD47 and PD-L1 expression was retrospectively assessed in 191 resected NSCLC specimens via immunohistochemistry. Forty-six patients with pulmonary infectious diseases were enrolled as the control group. The infiltration of macrophages (M2 and M1) and CD8+ T-lymphocytes was evaluated via dual-immunofluorescence staining. Targeted DNA sequencing was performed on NSCLC specimens. Survival analysis was performed using the Cox model. RESULTS: Using 2+/3+ as a CD47 positive (CD47pos) expression cut-off, the prevalence of CD47pos expression in NSCLC was 33.0% (63/191), significantly higher than in pulmonary infectious diseases. CD47pos expression was significantly higher in female, non-smoking and adenocarcinoma patients (p=0.020, p<0.001 and p<0.001, respectively). Furthermore, CD47pos expression was significantly correlated with epidermal growth factor receptor mutation (p<0.001). The expression of CD47 (H-score) in NSCLC was negatively correlated with tumour PD-L1 expression (p=0.0346) and tumour mutation burden (p=0.0107). CD47pos expression was independently correlated with poor disease-free survival in patients with resected NSCLC in multivariate Cox regression analysis (p=0.035). CONCLUSION: This study revealed the demographic, molecular and immuno-microenvironment characteristics of CD47 expression in NSCLC. We identified tumour CD47pos expression as an independent prognostic factor for recurrence in resected NSCLC. Our findings illustrate the potential of anti-CD47 treatment in NSCLC.

Association between ABCB1 (3435C>T) polymorphism and susceptibility of colorectal cancer: A meta-analysis.

Studies on the relationship between ABCB1 3435C>T polymorphism (rs1045642) and colorectal cancer (CRC)susceptibility have yielded inconclusive results. To clarify this issue, we undertook a meta-analysis to investigate the relationship between rs1045642 and CRC risk.Three electronic scientific publication databases (Cochrane Library, Pubmed, Embase) were screened using specific search terms. Relevant literature was identified using literature traceability methods. Selected publications were evaluated according to the inclusion and exclusion criteria. Effect size information (odds ratio and the corresponding 95% confidence interval [CI]) was obtained following quality assessment and data extraction from the included publications, and a meta-analysis conducted. Statistical analysis was performed with the Stata sofz (Version 13.0) software.Overall, 17 case-control studies involving 7129 CRC patients and 7710 healthy control subjects satisfied the criteria for inclusion in the meta-analysis. There was no significant association between ABCB1 3435C>T polymorphism and CRC risk in any of the genetic models. In the CC versus CT model (I = 20.9%, Pheterogeneity = .276), CC versus CT + TT model (I = 45.6%, Pheterogeneity = .102) and CT versus CC + TT model (I = 17.8%, Pheterogeneity = .298) analyses, between-study heterogeneities were detected as significant in Asian populations. In the CT versus TT model (I = 24%, Pheterogeneity = .254) and CC + CT versus TT model (I = 0, Pheterogeneity = .55), between-study heterogeneities were found to be significant in groups of different populations.The meta-analysis described here suggests that the ABCB1 3435C>T polymorphism is not related to CRC susceptibility.

Prognostic role of circulating tumor cells in patients with EGFR-mutated or ALK-rearranged non-small cell lung cancer.

BACKGROUND: Circulating tumor cell (CTC) counts at baseline and follow-up are an independent prognostic factor in patients receiving standard chemotherapy for non-small cell lung cancer (NSCLC). This study further explored the role of CTCs in EGFR-mutated and ALK-rearranged NSCLC patients administered targeted therapies as first-line treatment. METHODS: CTCs were enumerated with a novel high-efficiency detection method from the blood of 43 patients with EGFR-mutated or ALK-rearranged NSCLC at baseline and at disease-progression. Patients were stratified into favorable and unfavorable groups with baseline CTC counts of < 8 or ≥ 8 CTCs/3.2 mL, respectively. RESULTS: A total of 76.7% of the patients were positive for ≥ 2 CTCs /3.2 ml blood at baseline. The median progression-free survival (PFS) and overall survival (OS) rates of the favorable compared to the unfavorable group were longer (11.6 vs. 8.5 months, P = 0.004 for PFS; 21.00 vs. 17.7 months, P = 0.013 for OS). Multivariate analysis demonstrated that baseline CTC count was a strong predictor of PFS (hazard ratio 2.835; 95% confidence interval 1.240-6.483; P = 0.014) and OS (hazard ratio 3.317; 95% confidence interval 1.360-8.092; P = 0.008). CONCLUSION: Baseline CTC count could be a predictive biomarker for EGFR-mutated and ALK-rearranged NSCLCs, which allows for better guidance and monitoring of patients over the course of molecular targeted therapies.

Prognostic significance of circulating tumor cells in non-small cell lung cancer patients undergoing chemotherapy.

The utility of circulating tumor cells (CTCs) as prognostic biomarkers in non-small cell lung cancer (NSCLC) is inconclusive due to the limitations of current CTC detection methods. Using a novel high-efficiency detection method, we determined the ability of CTCs to predict survival and chemotherapeutic responses in NSCLC. In 127 patients with advanced NSCLC, CTCs were counted and analyzed at baseline and during follow-up. Median overall survival (OS) and progression-free survival (PFS) were longer in patients with baseline CTC counts <8 CTCs/3.2 mL (20.0 vs. 10.4 months [P = 0.009] and 7.2 vs. 5.5 months [P < 0.001], respectively). Patients with post-treatment increases in the CTC count had poorer OS and PFS than those without increases (12.0 vs. 13.3 months [P = 0.028] and 5.2 vs. 6.4 months [P = 0.022], respectively). There was no association between the baseline CTC count and chemotherapeutic response (P = 0.734). However, the rate of progressive disease in patients with and without post-treatment increases in the CTC count were 15.6% and 2.4% (P = 0.042), respectively. The baseline CTC count and the change in the CTC count during treatment were both valuable prognostic indicators for NSCLC.

Biomimetically inspired asymmetric total synthesis of (+)-19-dehydroxyl arisandilactone A.

Complex natural products are a proven and rich source of disease-modulating drugs and of efficient tools for the study of chemical biology and drug discovery. The architectures of complex natural products are generally considered to represent significant barriers to efficient chemical synthesis. Here we describe a concise and efficient asymmetric synthesis of 19-dehydroxyl arisandilactone A-which belongs to a family of architecturally unique, highly oxygenated nortriterpenoids isolated from the medicinal plant Schisandra arisanensis. This synthesis takes place by means of a homo-Michael reaction, a tandem retro-Michael/Michael reaction, and Cu-catalysed intramolecular cyclopropanation as key steps. The proposed mechanisms for the homo-Michael and tandem retro-Michael/Michael reactions are supported by density functional theory (DFT) calculation. The developed chemistry may find application for the synthesis of its other family members of Schisandraceae nortriterpenoids.

Mechanism of Fuzheng Kang'ai Formula Regulating Tumor Microenvironment in Non-Small Cell Lung Cancer / 中国结合医学杂志

OBJECTIVE@#To study the mechanism of Chinese herbal medicine Fuzheng Kang'ai Formula (, FZKA) on tumor microenvironment (TME).@*METHODS@#CIBERSORTx was used for analysis of TME. Traditional Chinese Medicine Systems Pharmacology and Analysis Platform was applied to identify compounds-targets network and the Cancer Genome Atlas (TCGA) was employed to identify the differential expression genes (DEGs) between tumor and paracancerous tissues in lung adenocarcinoma (LUAD) from TCGA-LUAD. Additionally, DEGs with prognosis in LUAD was calculated by univariable and multivariate Cox regression. The core targets of FZKA were analyzed in lung adenocarcinoma TME. Protein-protein interaction database was employed to predict down-stream of target. Quantitative reverse transcription polymerase chain reaction was employed for biological experiment in A549, H1299 and PC9 cell lines.@*RESULTS@#The active and resting mast cells were significantly associated with prognosis of LUAD (P<0.05). Of the targets, CCNA2 as an important target of FZKA (hazard ratio=1.41, 95% confidential interval: 1.01-2.01, P<0.05) was a prognostic target and significantly associated with mast cells. CCNA2 was positively correlated with mast cell activation and negatively correlated with mast cell resting state. BCL1L2, ACTL6A and ITGAV were down-stream of CCNA2, which were validated by qRT-PCR in A549 cell.@*CONCLUSION@#FZKA could directly bind to CCNA2 and inhibit tumor growth by regulating CCNA2 downstream genes and TME of NSCLC closely related to CCNA2.

[Advances on Driver Mutations of Small Cell Lung Cancer].

Small cell lung cancer (SCLC) is an aggressive tumor and prognosis remains dismal. Screening for the targetable driver mutations of this malignant tumor contributes to improve the therapeutic approaches and outcome. This review will report the advances on some latest driver mutations.