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Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)–associated epithelial malignancy characterized by the presence of prominent infiltration of lymphocytes, including natural killer (NK) cells. Although NK cells can directly target EBV-infected tumor cells without restriction by the MHC, EBV-positive (EBV+) NPC cells often develop resistance mechanisms that allow them to evade immune surveillance by NK cells. Elucidating the mechanisms involved in EBV-induced NK-cell dysfunction will contribute to the design of novel NK cell–based immunotherapies to treat NPC. Herein, we confirmed that the cytotoxic function of NK cells was impaired in EBV+ NPC tissues and found that EBV infection–induced expression of B7-H3 in NPC negatively correlated with NK-cell function. The inhibitory effect of EBV+ tumor expression of B7-H3 on NK-cell function was clarified in vitro and in vivo. Mechanistically, activation of the PI3K/AKT/mTOR signaling pathway via EBV latent membrane protein 1 (LMP1) was responsible for EBV infection–induced upregulation of B7-H3 expression. In an NPC xenograft mouse model with adoptive transfer of primary NK cells, deletion of B7-H3 on tumor cells in combination with anti–PD-L1 treatment restored NK cell–mediated antitumor activity and significantly improved the antitumor efficacy of NK cells. On the basis of our findings, we conclude that EBV infection can inhibit NK cell–mediated antitumor function by inducing upregulation of B7-H3 expression and provide a rationale for NK cell–based immunotherapies in combination of PD-L1 blockade and overcoming the immunosuppression of B7-H3 to treat EBV-associated NPC.

The selection of patients for immunotherapy remains challenging given the lack of highly specific and highly sensitive biomarkers. Kirsten rat sarcoma (Clinical data were extracted from medical records of patients with advanced NSCLC at the First Affiliated Hospital of Guangzhou Medical University in China between January 2019 and March 2020. Overall survival (OS) and progression-free survival (PFS) rates were compared via log-rank tests, and independent prognostic factors were identified via Cox regression.Patients with advanced NSCLC without driver alterations who were treated with ICI and platinum-based chemotherapy (N=80) were identified, including 28.7% withThis work provides evidence that

Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)–associated epithelial malignancy characterized by the presence of prominent infiltration of lymphocytes, including natural killer (NK) cells. Although NK cells can directly target EBV-infected tumor cells without restriction by the MHC, EBV-positive (EBV+) NPC cells often develop resistance mechanisms that allow them to evade immune surveillance by NK cells. Elucidating the mechanisms involved in EBV-induced NK-cell dysfunction will contribute to the design of novel NK cell–based immunotherapies to treat NPC. Herein, we confirmed that the cytotoxic function of NK cells was impaired in EBV+ NPC tissues and found that EBV infection–induced expression of B7-H3 in NPC negatively correlated with NK-cell function. The inhibitory effect of EBV+ tumor expression of B7-H3 on NK-cell function was clarified in vitro and in vivo. Mechanistically, activation of the PI3K/AKT/mTOR signaling pathway via EBV latent membrane protein 1 (LMP1) was responsible for EBV infection–induced upregulation of B7-H3 expression. In an NPC xenograft mouse model with adoptive transfer of primary NK cells, deletion of B7-H3 on tumor cells in combination with anti–PD-L1 treatment restored NK cell–mediated antitumor activity and significantly improved the antitumor efficacy of NK cells. On the basis of our findings, we conclude that EBV infection can inhibit NK cell–mediated antitumor function by inducing upregulation of B7-H3 expression and provide a rationale for NK cell–based immunotherapies in combination of PD-L1 blockade and overcoming the immunosuppression of B7-H3 to treat EBV-associated NPC.

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Purpose:Clonal architecture is fundamental for the understanding of cancer biology and therapy; however, multiregional sampling in advanced-stage cancers is not always applicable. This prospective clinical trial was to investigate whether paired tissue and circulating tumor DNA (ctDNA) could describe the clonal architecture of advanced non–small cell lung cancer (NSCLC) and its association with clinical outcome (NCT03059641).Patients and Methods:Paired tumor and plasma ctDNA samples were sequenced by target-capture deep sequencing of 1,021 genes. Clonal dominance analysis was performed on the basis of PyClone.Results:Overall, 300 treatment-naïve patients with stage IIIB–IV NSCLC were recruited from 14 centers. Of the 94 patients with available ctDNA data for EGFR clonal architecture analysis, 72 (76.6%) showed EGFR as the dominant clone. The median progression-free survival was longer for these patients than for the 22 patients whose EGFR was nondominant clone [11 vs. 10 months; HR, 0.46; 95% confidence interval (CI), 0.24–0.88; P = 0.02]. The difference was more significant if both tissue and ctDNA defined EGFR as dominant clone (n = 43) versus those not (n = 8; 11 vs. 6 months; HR, 0.13; 95% CI, 0.04–0.50; P = 0.003). Moreover, multivariate Cox proportional HR analysis demonstrated EGFR clonal architecture as an independent prognostic indicator of the efficacy of EGFR-tyrosine kinase inhibitors (TKIs).Conclusions:Paired tissue and ctDNA could be analyzed for clonal architecture in advanced cancer. EGFR mutations do not always make up a dominant clone in advanced NSCLC, which was associated with the efficacy of EGFR-TKIs in NSCLC.

Other driver mutations in 22 discordant cases.

Kaplan-Meier curves for progression-free survival (A) EGFR detected in ctDNA/tissue of the 112 patients for EGFR-TKI efficacy analysis. (B) EGFR dominance analysis according to ctDNA or tissue of patients in (A). (C) Discordance of EGFR dominance analyzed by ctDNA or tissue of the 73 patients with EGFR detected in both ctDNA and tissue (D) Progression-free survival according to mutation clusters in ctDNA (n=85). (E) Progression-free survival according to mutation clusters in tissue (n=100). ctDNA=circulating free tumor-derived DNA. HR=hazard ratio.

Background ROS1-rearranged lung cancers benefit from first-line crizotinib therapy; however, clinical and molecular factors that could affect crizotinib efficacy in ROS1-rearranged lung cancers are not yet well-elucidated. Our retrospective study aimed to compare the efficacy of chemotherapy and crizotinib in the first-line treatment of ROS1-rearranged advanced lung cancer and evaluate various clinical and molecular factors that might impact crizotinib efficacy in real-world practice. Methods Treatment responses, survival outcomes, and patterns of disease progression were analyzed for 235 patients with locally advanced to advanced disease who received first-line chemotherapy (n = 67) or crizotinib (n = 168). Results The overall response rate was 85.7% (144/168) for first-line crizotinib and 41.8% (28/67) for chemotherapy. Patients treated with first-line crizotinib (n = 168) had significantly longer median progression-free survival (PFS) than chemotherapy (n = 67) (18.0 months vs. 7.0 months, p CD74-ROS1 (n = 90) had significantly shorter median PFS with crizotinib than those harboring non-CD74 ROS1 fusions (n = 69) (17.0 months vs. 21.0 months; p = 0.008). Patients with baseline brain metastasis (n = 45) had a significantly shorter PFS on first-line crizotinib than those without brain metastasis (n = 123) (16.0 months vs. 22.0 months; p = 0.03). At progression, intracranial-only progression (n = 40), with or without baseline CNS metastasis, was associated with longer median PFS than those with extracranial-only progression (n = 64) (19.0 months vs. 13.0 months, p TP53 mutations were the most common concomitant mutation, detected in 13.1% (7/54) of patients with CD74-ROS1 fusions, and 18.8% (6/32) with non-CD74 ROS1 fusions. Patients with concomitant TP53 mutations (n=13) had significantly shorter PFS than those who had wild-type TP53 (n = 81) (6.5 months vs. 21.0 months; p n = 9) (11.0 months vs 24.0 months; p = 0.0167) or concomitant tumor suppressor genes (i.e., TP53, RB1, or PTEN) (n = 25) (9.5 months vs 24.0 months; p n = 58). Conclusion Our results demonstrate that baseline brain metastatic status and various molecular factors could contribute to distinct clinical outcomes from first-line crizotinib therapy of patients with ROS1-rearranged lung cancer. Clinical trials registration CORE, NCT03646994

Purpose: Clonal architecture is fundamental for the understanding of cancer biology and therapy; however, multiregional sampling in advanced-stage cancers is not always applicable. This prospective clinical trial was to investigate whether paired tissue and circulating tumor DNA (ctDNA) could describe the clonal architecture of advanced non–small cell lung cancer (NSCLC) and its association with clinical outcome (NCT03059641). Patients and Methods: Paired tumor and plasma ctDNA samples were sequenced by target-capture deep sequencing of 1,021 genes. Clonal dominance analysis was performed on the basis of PyClone. Results: Overall, 300 treatment-naïve patients with stage IIIB–IV NSCLC were recruited from 14 centers. Of the 94 patients with available ctDNA data for EGFR clonal architecture analysis, 72 (76.6%) showed EGFR as the dominant clone. The median progression-free survival was longer for these patients than for the 22 patients whose EGFR was nondominant clone [11 vs. 10 months; HR, 0.46; 95% confidence interval (CI), 0.24–0.88; P = 0.02]. The difference was more significant if both tissue and ctDNA defined EGFR as dominant clone (n = 43) versus those not (n = 8; 11 vs. 6 months; HR, 0.13; 95% CI, 0.04–0.50; P = 0.003). Moreover, multivariate Cox proportional HR analysis demonstrated EGFR clonal architecture as an independent prognostic indicator of the efficacy of EGFR-tyrosine kinase inhibitors (TKIs). Conclusions: Paired tissue and ctDNA could be analyzed for clonal architecture in advanced cancer. EGFR mutations do not always make up a dominant clone in advanced NSCLC, which was associated with the efficacy of EGFR-TKIs in NSCLC.

Immunotherapy has provided a novel therapeutic option for lung cancer but studies involving patients with advanced non-small cell lung cancer (NSCLC) coupled with various degrees of comorbid chronic obstructive pulmonary disease (COPD) are limited. Thus, we performed a retrospective cohort study to optimize the use of immunotherapy in this special population.We enrolled a total of 99 patients with advanced (stage IIIB/C-IV) NSCLC with comorbid COPD who had received immune checkpoint inhibitors (ICIs) according to the inclusion and exclusion criteria. They were divided into four groups according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline criteria as follows: no COPD group (nThere were statistically significant differences in the incidence of irAEs among the four groups (P=0.003). The incidence of irAEs in patients with no COPD (nImmunotherapy should be selected with caution for advanced NSCLC patients with comorbid severe COPD, considering the limited efficacy and the increased risk of immune-related adverse events related to the immune-checkpoint inhibitors administration in this special population.

Background and Objective: Patients with small cell lung cancer (SCLC) comorbid COPD are not rare clinically, but related studies are limited, and there is no consensus on optimal treatment and prognostic factors for these patients. In this study, the clinical characteristics and the efficacy of different treatment regimens of patients with SCLC comorbid COPD were analyzed retrospectively to explore the optimal regimens and prognostic factors. Patients and methods: A retrospective study was conducted on 97 patients with SCLC who received first-line etoposide combined with platinum chemotherapy from January 1, 2013 to September 31, 2020 in the first affiliated hospital of Guangzhou Medical University.patients were divided into COPD and non-COPD group, progression-free survival (PFS) and overall survival (OS) were compared between the two groups and prognostic factors of SCLC were analyzed. Furthermore, the differences of PFS and OS and prognostic factors were analyzed in the sub-group of COPD patients (COPD treated group and COPD untreated group).Results: There were no significant difference in median PFS (7.4 months VS 7.6 months, p = 0.327) and OS (11.2 months VS 14.5 months, p = 0.081) between COPD group (N = 61) and non-COPD group (N = 36). In the COPD group, 21 patients (34.4%) received COPD treatment. And the median OS of COPD treated group was was longer than that of COPD untreated group (13.4 months VS 10.6 months, p = 0.032), but there existed no significant difference in PFS between the two groups (7.4 months VS 7.0 months, p = 0.648). In patients with SCLC comorbid COPD, multivariate regression analysis indicated that COPD was not a risk factor for OS, while extensive stage was independently associated with poorer OS and chest radiotherapy was independently associated with longger OS.Conclusion: For SCLC patients who received first-line cytotoxic chemotherapy, COPD does not impair prognosis, and COPD treatment was benefit for OS of those comorbid COPD, receiving both COPD treatment and chemotherapy was a preferred option as first-line treatment for patients with SCLC comorbid COPD. Extensive stage and thoracic radiotherapy are independent prognostic factors for OS in patients with SCLC comorbid COPD.

Objective The study aimed to analyze the efficacy and safety of combination regimen of anlotinib and S-1 for Chinese patients with EGFR mutation-negative advanced squamous cell lung cancer (SqCLC) with poor performance status (PS,2-3) after progression of second-line or later-line chemotherapy. Methods Clinical data of 70 SqCLC patients with PS scores of 2-3 treated in the First Affiliated Hospital of Guangzhou Medical University between January 1, 2018 to September 31, 2019 who failed second- or more-line treatment were analysed retrospectively. The patients were divided into two treatment groups: anlotinib (12mg) plus S-1 (25mg) combination group and anlotinib (12mg) monotherapy group. The efficacy and adverse reactions of the two groups were compared. Results In terms of the short-term efficacy, there were no significant differences in objective response rate (ORR) (20.0% vs 10.0%, p = 0.464) and disease control rate (DCR) (75.0% vs 60.0%, p = 0.181) between the two groups. As for the long-term efficacy, there was no significant difference in progression-free survival (PFS) between the two groups (3.87±0.29 months vs 3.00±0.24 months, p=0. 11). The overall survival (OS) of patients in the combination group was longer than S1 group (8.07±0.56 months vs 6.17±0.42 months, p=0.022). Conclusion Advanced SqCLC patients with higher PS scores still benefit from anlotinib and S-1 combination regimen, even after they failed second-line or later-line systemic treatment.

The tumor microenvironment (TME) constitutes a complex milieu of cells and cytokines that maintain equilibrium between tumor progression and prognosis. However, comprehensive analysis of the TME and its clinical significance in head and neck squamous cell carcinoma (HNSCC) remains to be unreported. In this study, based on large-scale RNA sequencing data pertaining to single nucleotide variants (SNVs) and copy number variations (CNVs) in HNSCC patients from The Cancer Genome Atlas database, we analysed subpopulations of infiltrating immune cells and evaluated the role of TME infiltration pattern (TME score) in assessing immunotherapy outcome. TME signature genes involved in several inflammation and immunity signalling pathways were observed in the TME score subtype, which were considered immunosuppressive and potentially responsible for significantly worse prognosis. In comparison with SNV- and CNV-mediated tumor mutation burden, TME score can significantly differentiate between high- and low-risk HNSCC and predict immunotherapy outcome. Our data provide clarity on the comprehensive landscape of interactions between clinical characteristics of HNSCC and tumor-infiltrating immune cells. TME score seems to be a useful biomarker that can predict immunotherapy outcome in HNSCC patients.

To understand the molecular mechanism of tumorigenesis of pulmonary lymphoepithelioma-like carcinoma and explore potential therapeutic strategies, we investigated the genomic profiles and PD-L1 expression of 29 Chinese pulmonary lymphoepithelioma-like carcinoma patients at various stages. We performed capture-based targeted sequencing on tissue samples collected from 27 patients with sufficient samples using a panel consisting of 520 cancer-related genes, spanning 1.64 Mb of the human genome. We identified 184 somatic mutations in 109 genes from 26 patients. One patient had no mutations detected by this panel. Copy number variations were detected in 52% (14/27) of the patients, with a majority having advanced-stage disease (10/14). Except for the detection of ERBB2 amplification and KRAS mutation in two patients, no other classic lung cancer driver mutations were detected. Interestingly, 78% (21/27) of the patients had mutations in epigenetic regulators. Of the 184 mutations identified, 51 occurred in 29 epigenetics-related genes. Furthermore, we performed PD-L1 immunohistochemistry staining using the Dako 22C3 assay and demonstrated that 69% (20/29) of the cohort had positive PD-L1 expression, of which three patients received and benefited from a PD-1 inhibitor. In conclusion, we elucidated a distinct genomic landscape associated with pulmonary lymphoepithelioma-like carcinoma with no classic lung cancer driver mutation but an enrichment of mutations in epigenetic regulators. The detection of high PD-L1 expression and lack of any canonical druggable driver mutations raises the potential of checkpoint immunotherapy for pulmonary lymphoepithelioma-like carcinoma.

Dissolved methane (CH4) was measured at 9 stations along a transect at 75° S in the Ross Sea during austral summer in January 2020. CH4 undersaturation (mean: 82 ± 20 %) was found in the water column, with a mean air-sea CH4 flux density of −0.58 ± 0.48 μmol m−2 day−1, which suggests that the Ross Sea was a net sink for atmospheric CH4 during the austral summer. Simple box-model calculations revealed that the CH4 depletion should occur in the surface mixed layer because of CH4 oxidation and advection of CH4-poor waters. We propose that freshwater injection caused by sea-ice melting in summer dilutes CH4 concentrations within the surface layer and thus increases its potential for atmospheric CH4 uptake in the Ross Sea. Thus, we argue that both CH4 consumption and sea-ice melting are important drivers of CH4 undersaturation, which implies that the high-latitude area of the Southern Ocean is a sink for atmospheric CH4. We estimated that the Southern Ocean (> 65° S) takes up about 0.02 % of the global CH4 emissions and thus represents a minor sink for atmospheric CH4.

Nitrous oxide (N2O) is the third most important greenhouse gas in the atmosphere, and the ocean is an important source of N2O. As the Arctic Ocean is strongly affected by global warming, rapid ice melting can have a significant impact on the N2O pattern in the Arctic environment. To better understand this impact, N2O concentration in ice core and underlying seawater (USW) was measured during the seventh Chinese National Arctic Research Expedition (CHINARE2016). The results showed that the average N2O concentration in first-year ice (FYI) was 4.5 ± 1.0 nmol kg−1, and that in multi-year ice (MYI) was 4.8 ± 1.9 nmol kg−1. Under the influence of exchange among atmosphere-sea ice-seawater systems, brine dynamics and possible N2O generation processes at the bottom of sea ice, the FYI showed higher N2O concentrations at the bottom and surface, while lower N2O concentrations were seen inside sea ice. Due to the melting of sea ice and biogeochemical processes, USW presented as the sink of N2O, and the saturation varied from 47.2% to 102.2%. However, the observed N2O concentrations in USW were higher than that of T-N2OUSW due to the sea–air exchange, diffusion process, possible N2O generation mechanism, and the influence of precipitation, and a more detailed mechanism is needed to understand this process in the Arctic Ocean.

Long noncoding RNAs (lncRNAs) are associated with tumorigenesis and linked to altered metabolism. Our previous studies have identified an oncogenic function of lncRNA Linc00173 in small cell lung cancer (SCLC), while the detailed mechanisms remain to be fully clarified. We show that Linc00173 plays a critical role for chemoresistance in SCLC through reprogramming glucose metabolism. By phosphorylating Y-Box Binding Protein 1 (YB1), Linc00173 stimulates the translation of YB1 bound glucose metabolic enzymes HK2 and G6PD, which activates glycolysis and the pentose phosphate pathway (PPP). The expression levels of Linc00173 and HK2/G6PD show a positive correlation in 46 tissue samples from SCLC patients. Furthermore, we demonstrated that the inhibitors of HK2 and G6PD, 3-BrPA and RRx-001, exhibit a synergistic antitumor effect with chemotherapy both in vitro and in vivo, including a PDX model. For the first time, we identified the mechanism of Linc00173/YB1 axis-induced glucose metabolic rewiring in SCLC, indicating that glucose metabolic enzymes HK2 and G6PD may be potential therapeutic targets for SCLC treatments.

Rapid warming and loss of sea ice in the Arctic Ocean could play an important role in the dissolution and emission of greenhouse gas nitrous oxide (N2O). We investigated dissolved N2O in spatiotemporal distribution on the northeastern Bering Sea shelf (NEBS) in the summer of 2012. The results showed that N2O concentrations were higher in the Chirikov Basin (mean ± SD, 14.8 ± 2.4 nmol/L) than in the south of St. Lawrence Island (mean ± SD, 17.7 ± 2.3 nmol/L). In the Chirikov Basin, N2O displayed a decreasing distribution pattern from west (~20.4 nmol/L) to east (~12.9 nmol/L). In the area south of St. Lawrence Island, N2O almost presented a two-layer structure, although it showed a vertically homogeneous distribution in the inner shelf. In the cold bottom water, the N2O was affected mainly by in situ production or sediment emission. Longer resident time may cause N2O accumulation in the cold bottom water. The calculated sea–air flux (−1.6~36.2 μmol/(m2·d)) indicates that the NEBS is an important potential source of atmospheric N2O and could play an important role in global oceanic N2O emission with intensifying global issues.

Background Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare subtype of non-small cell lung cancer associated with Epstein-bar virus (EBV) infection. Epithelioid granuloma (EG) has been more scarcely reported and frequently misdiagnosed. Methods Data were collected from January 2013 to October 2019. Of 227 patients diagnosed as having PLELC, 22 patients had EG. We analyzed their clinical features, pathological characteristics and treatment and a comparison between PLELC patients complicated with or without EG was made. Results Twenty-two patients had complicated with EG (9.6%). The median age was 50 years (38–67 years). There were more females than males (1.4:1). Most patients were at early stage (68.2%) with nonspecific manifestations and lack of Rich-Lewis phenomenon. Compared with the 205 patients complicated without EG, there were no significant difference among age (t=0.938, P=0.349), gender (χ2=0.898, P=0.343), initial symptoms (χ2=2.684, P=0.443), smoking status (χ2=0.210, P=0.647), diameter of tumor(t=0.993, P=0.332) and performance status (H=0.971, P=0.615). EG was often located inside or adjacent to the tumor (71.4%). Specific staining was negative, whereas in situ hybridization staining of EBV-encoded RNA was consistently positive. Most patients complicated with EG received multimodality therapy including surgery, neo-adjuvant/adjuvant chemotherapy or palliative chemotherapy and none of them received anti-TB therapy. Compared with the 205 patients complicated without EG, there were no significant difference among tumor stage, DFS (median, not reached, P=0.914), PFS (median, 12.3 months, P=0.848), OS (median, not reached, P=0.737) and treatment including anti-tumor therapy and anti-TB therapy. During follow-up duration for 14.6 months (range, 2.1–94.7 months), none of the patients had occurrence, progression or relapse of tuberculosis, regardless whether anti-tuberculosis therapy was initiated. Conclusions PLELC complicated with EG was lack of Rich-Lewis phenomenon and specific clinical characteristics compared with those without EG. EG might be caused by immunological hypersensitivity to tumor cells or EBV infection but not pulmonary tuberculosis. PLELC complicated with EG could be treated with chemotherapy and surgery. However, anti-tuberculosis therapy was unnecessary.

Background Medulloblastoma is an aggressive brain tumor mostly found in children, few studies on pathogenic germline mutations predisposing this disease was reported. Case presentation We present an 11-year-old male with medulloblastoma, who harbors a de novo PHOX2B germline mutation as detected by whole exome sequencing (WES). Family history was negative. Sanger sequencing confirmed this mutation in peripheral blood, hair bulbs, urine and saliva. Identification of novel germline mutations is beneficial for childhood cancer screening. Conclusions This case revealed a de novo PHOX2B germline mutation as a potential cause of medulloblastoma in a child and suggests familial germline variant screening is useful when an affected family is considering having a second child.

Introduction: Circulating non-coding RNA is an ideal source to discover novel biomarkers for non-invasive screening. However, studies for the discovery of universal miRNAs in serum and exosomes for breast cancer early diagnosis are limited. Methods: Based on bioinformatic analysis, in vitro and in vivo studies were performed to understand the role of identified hsa-miR-423-5p in cancer proliferation, migration, cancer stem cell properties. Next, global non-coding RNA expression profiles in blood serum and exosome were performed. hsa-miR-423-5p expression from a total of 356 peripheral blood samples was evaluated and the association of hsa-miR-423-5p expression with clinical characteristics, sensitivity and specificity for breast cancer diagnosis were assessed. Results: The expression of serum and exosomal hsa-miR-423-5p is abnormally increased in breast cancer. Suppression of hsa-miR-423-5p inhibited cell proliferation and invasion in both T47D and MDA-MB-231 breast cancer cell lines, and tumor growth in vivo. Compared with 113 healthy women, quantification analysis of hsa-miR-423-5p in 224 breast cancer samples confirmed the abnormal expression. Serum hsa-miR-423-5p was significantly associated with the clinical stage (P=0.001) and Ki-67 level (P=0.004). Conclusions: A translational bioinformatics analysis procedure and validation by in vitro, in vivo, and clinical samples reveal that hsa-miR-423-5p could be used as a non-invasive breast cancer biomarker.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD) with poor performance status (PS) are common in clinical practice with few related studies. Present studies have found that weekly low-dose docetaxel or gemcitabine combined with platinum is suitable for elderly or poor PS patients with advanced NSCLC. METHODS: Untreated advanced driver mutation-negative NSCLC patients with COPD and PS ≥2 were enrolled in this double-blind randomized trial. Both groups controlled their COPD symptoms according to the GOLD guidelines. The anti-tumor regimens included docetaxel (37.5 mg/m(2), D1, D8)/carboplatin (AUC 5.0) (DC group) and gemcitabine (1,000 mg/m(2), D1, D8)/carboplatin (AUC 5.0) (GC group) were used every 3 weeks with continuous chemotherapy for 4–6 cycles or until disease progression. The primary endpoints were progression-free survival (PFS), and overall survival (OS). RESULTS: Among the 52 patients (DC, n=25; GC, n=27), the median follow-up time was 12.3 months. There was no significant difference in tumor overall response rate (ORR; DC, 20.0% vs. GC, 22.2%, P=0.845) and disease control rate (DCR; DC, 72.0% vs. GC, 74.1%, P=0.064) between the 2 groups. The median PFS (GC, 6.5 vs. DC, 5.5 months; P=0.296) and the median OS (GC, 14.9 vs. DC, 12.3 months; P=0.548) of the GC group was slightly longer than the DC group. The main adverse reactions were myelosuppression and there were few adverse reactions of grade 3–4. Compared with the anti-tumor therapy only group in previous literature, the median PFS in this study was longer (6.2 months, 95% CI: 3.533–6.733 vs. 3.5 months, 95% CI: 2.432–4.568; P=0.589). There was also no significant difference in median OS and median PFS between the 2 groups (14.0 vs. 15.0 months, P=0.718). Chemotherapy cycle (P

Nonbacterial thrombotic endocarditis (NBTE) is a rare disease that most often found post mortem. Malignant neoplasms, particularly adenocarcinomas, are the common underlying diseases associated with NBTE. In recent years, remarkable advances in targeted therapy have been made, but the effectiveness in treating NBTE in patients with severe lung cancer is poorly reported. Here we present two cases of severe NBTE in patients with stage IV lung adenocarcinoma harboring driver gene mutations, one with EGFR mutation, the other with positive ALK fusion oncogene. Both patients scored 4 according to the Cooperative Oncology Group performance status (ECOG PS) before the initiation of targeted therapies and anticoagulation therapies. Both patients showed significant improvement: the vegetations in their hearts vanished, their ECOG PS score changed from 4 to 3. We also discuss the current understanding of NBTE, including its epidemiology, pathogenesis, clinical presentation, evaluation, diagnosis, and treatment. Our report highlights the necessity of early and timely diagnosis of NBTE and gene classification for NSCLC patients (ECOG PS score ≥3), the importance of concurrent therapy for the cancer and its complications, and further stresses the effectiveness of targeted therapy for NBTE in patients with severe lung cancer harboring driver gene mutations.

Objective NUT midline carcinoma (NMC), a rare type of squamous cell carcinoma, is genetically characterised by NUT midline carcinoma family member 1 (NUTM1) gene rearrangement. NMC can arise from the lungs; however, there is no standard for the management of primary pulmonary NMC. This study aimed to confirm the clinical features and report the treatments, especially with immune checkpoint inhibitors (ICIs), and outcomes of patients with primary pulmonary NMC. Methods A retrospective review of patients with primary pulmonary NMC was performed in the First Affiliated Hospital of Guangzhou Medical University between January 2015 and December 2018. Clinical manifestations as well as radiographic and pathological findings were recorded. Whole-exome sequencing (WES), a predictor for ICI response, was used to determine the tumour mutational burden (TMB). Treatments, especially by immune checkpoint blockade, and patient survival were analysed. Results Seven patients with primary pulmonary mass (four men and three women) with a mean age of 42 years (range, 23–74) who were diagnosed with NMC according to NUT immunohistochemistry staining were included for analysis. One patient had a rare fusion of CHRM5-NUTM1 by tumour sequencing. A wide range of TMB (1.75–73.81 mutations/Mbp) was observed. The initial treatments included chemotherapy (5/7, 71.4%), surgery (1/7, 14.3%), and radiotherapy (1/7, 14.3%). Five patients (5/7, 71.4%) received ICIs (programmed cell death protein 1 [PD1]/programmed cell death ligand 1 [PDL1] monoclonal antibody) as second- or higher-line treatments. The median overall survival (OS) was 4.1 months (range, 1.5–26.7 months). Conclusions Patients with primary pulmonary NMC have a poor prognosis and chemotherapy is often preferred. Checkpoint immunotherapy is a good option as the second- or higher-line treatment. TMB seems to be not associated with OS.

BACKGROUND: Tracheal adenoid cystic carcinoma (TACC) is the second most common type of cancer in bronchial tumors with poor prognosis. Studies on the genomic profiles and tumor immune microenvironment (TIME) of TACC are still relatively rare. METHODS: Here, we performed whole-exome sequencing (WES), T cell repertoire (TCR) sequencing, and immunohistochemistry (IHC) on the resected tumors and matched peripheral blood leukocytes (PBLs) samples from 25 TACCs collected from April-2010 to Mar-2019. RESULTS: WES results revealed that LPAR3 and ALPI were recurrently mutated genes, with no classical lung cancer drivers in TACCs (n=8). The median tumor mutation burden (TMB) was 3.67, lower than other solid tumors. Unexpectedly, one patient showed high microsatellite instability (MSI). Recurrent copy number variations (CNVs) affected genes commonly involved in p53, cell cycle, and PI3K-Akt signaling pathways. For TCR estimators of 13 PBLs, the median clonality and Shannon index was 0.15 and 7.02, respectively. Shannon index showed marginally negative association with age (Pearson r =−0.53, P=0.062). Clonotype number and Shannon index of 7 TACC tissues were significantly lower than those of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) (Mann-Whitney test, both P