This study was aimed to detect the correlation among EGFR/KRAS status and PD-1/PD-L1 expression in non-small-cell lung cancer (NSCLC) patients. PD-1 and PD-L1 expressions were detected by immunohistochemistry in 100 surgically resected lung adenocarcinoma tissues and were statistically correlated with clinicopathological characteristics including EGFR and KRAS statuses. Besides, the overall survival (OS) times were analyzed. There was a statistical significances between PD-1 expression in tumor and KRAS status (P D 0.043), with a higher mutation rate in with lower PD-1 expression patients. There was a statistical significance between PD-L1 expression in tumor and EGFR status (P D 0.012), with a higher mutation rate in patients with lower PD-L1 expression. The OS of patients with EGFR mutation was significantly longer than those without EGFR mutation. The OS of patients with lower PD-L1 in tumor was significantly longer than those with higher PD-L1 expression. We found negative associations between PD-L1 expression in tumor and mutated EGFR status, as well as between PD-1 expression in tumor and mutated KRAS status.
Epigenetic regulation plays an important role in the occurrence, development and treatment of malignant tumors; and a great deal of attention has been paid to the histone methylation level in recent years. As a 230-kD epigenetic regulator, the histone H3 lysine 36 histone (H3K36) methyltransferase SETD2 is a key enzyme of the nuclear receptor SET domain-containing (NSD) family, which is associated with a specific hyperphosphorylated domain, a large subunit of RNA polymerase II (RNAPII), named RNAPII subunit B1 (RPB1), and SETD2 which methylates the ly-36 position of dimethylated histone H3 (H3K36me2) to generate trimethylated H3K36 (H3K36me3). SETD2 is involved in various cellular processes, including transcriptional regulation, DNA damage repair, non-histone protein-related functions and some other processes. Great efforts of high-throughput sequencing have revealed that SETD2 is mutated or its function is lost in a range of solid cancers, including renal cancer, gastrointestinal cancer, lung cancer, pancreatic cancer, osteosarcoma, and so on. Mutation, or functional loss, of the SETD2 gene produces dysfunction in corresponding tumor tissue proteins, leading to tumorigenesis, progression, chemotherapy resistance, and unfavorable prognosis, suggesting that SETD2 possibly acts as a tumor suppressor. However, its underlying mechanism remains largely unexplored. In the present study, we summarized the latest advances of effects of SETD2 expression at the mRNA and protein levels in solid cancers, and its potential molecular and cellular functions as well as clinical applications were also reviewed.
BackgroundB7-H4 is a novel B7 ligand that plays an important role in the T cell-mediated immune response as a negative regulator. Previous studies have suggested the aberrant expression of membrane B7-H4 in tumor cells. The aim of this study is to determine the expression levels of preoperative soluble B7-H4 (sB7-H4) in circulation and to investigate the correlations between sB7-H4 levels and clinicopathological parameters as well as the survival rate of patients with gastric cancer.MethodsBlood specimens from 132 patients with gastric cancer and 63 healthy volunteers were analyzed by sandwich enzyme-linked immunosorbent assay.ResultsMedian concentrations of sB7-H4 in patients with gastric cancer were significantly higher than those in healthy volunteers (16.85 versus 10.46 ng/mL; P = 0.008). Median levels of sB7-H4 were significantly correlated with tumor size, lymph node metastasis, the depth of tumor invasion and tumor-node-metastasis classification (P = 0.002, P = 0.001, P = 0.041 and P <0.001, respectively), but not with sex, age, tumor location or histological subtype (all P >0.05). Additionally, the overall survival rate was significantly lower in patients with high sB7-H4 levels when compared with low sB7-H4 levels (50.0% versus 77.3%, χ2 = 10.78, P = 0.001). Moreover, multivariate analysis demonstrated that the risk of death was significantly higher in patients with high sB7-H4 levels than in those with low sB7-H4 levels (P = 0.039).ConclusionssB7-H4 is a valuable blood marker for predicting the progression and prognosis of patients with gastric cancer.
Immunotherapy has become a crucial modality for non-small-cell lung cancer treatment. Recently, two immune checkpoints, PD-1 and PD-L1, have emerged as important targets for immunotherapy. Their antitumor efficacy has been confirmed by in vitro and in vivo studies. But the correlation between PD-1/PD-L1 expression and EGFR expression was controversial and needs more evidences to support the combination of PD-1/PD-L1 inhibitors and tyrosine kinase inhibitors.
Malignant solid tumors are the leading cause of death in humans, and epigenetic regulation plays a significant role in studying the mechanism of human solid tumors. Recently, histone lysine methylation has been demonstrated to be involved in the development of human solid tumors due to its epigenetic stability and some other advantages. The 90-kb protein methyltransferase nuclear receptor SET domain-containing 2 (NSD2) is a member of nuclear receptor SET domain-containing (NSD) protein lysine methyltransferase (KMT) family, which can cause epigenomic aberrations via altering the methylation states. Studies have shown that NSD2 is frequently over-expressed in multiple types of aggressive solid tumors, including breast cancer, renal cancer, prostate cancer, cervical cancer, and osteosarcoma, and such up-regulation has been linked to poor prognosis and recurrence. Further studies have identified that over-expression of NSD2 promotes cell proliferation, migration, invasion, and epithelial-mesenchymal transformation (EMT), suggesting its potential oncogenic role in solid tumors. Moreover, Gene Expression Profiling Interactive Analysis (GEPIA) was searched for validation of prognostic value of NSD2 in human solid tumors. However, the underlying specific mechanism remains unclear. In our present work, we summarized the latest advances in NSD2 expression and clinical applications in solid tumors, and our findings provided valuable insights into the targeted therapeutic regimens of solid tumors.
This study determined the levels of serum ferritin (SF) and carcinoembryonic antigen (CEA) in elderly patients with advanced primary lung cancer (PLC), and aimed to investigate the correlation between the SF level and clinical characteristics and compare the positive rates of SF and CEA levels in PLC patients and those in normal subjects. The SF and CEA levels of 69 elderly cases of advanced PLC and 63 elderly controls were determined by electrochemiluminescence method. The correlation between each independent clinicopathological characteristic and levels of SF and CEA was calculated. The positive rates of SF and CEA levels in PLC patients and those in normal subjects were compared. The results revealed that the level of SF in controls was significantly lower than those in patients with advanced LC (145.04 ± 141.77 vs. 293.57 ± 274.95 ng/ml, t = -3.845, P = 0.000). There was a statistically significant difference between SF level and gender, smoking, and regional lymph node metastasis, respectively (P < 0.05). The positive rate of SF combining with CEA was significantly higher than those of SF and CEA alone in patients with advanced PLC. High serum level of SF is helpful for diagnosing PLC in elderly patients and indicates poor prognosis.
Objectives: To investigate the association between ambient air pollutant exposure and daily hospital admissions for respiratory diseases in children in Guiyang.Methods: Clinical data of pediatric inpatients with respiratory disease from 2009 to 2016 in Guizhou Provincial People's Hospital and PM2.5, NO2, PM10, and SO2 concentration data were retrieved. A canonical correlation analysis (CCA) was applied to analyse the association between air pollutants and daily hospital admissions for respiratory diseases. A reproducibility analysis was applied to analyse the association between air pollution and the duration and direct cost of hospitalization. The support vector regression (SVR) method was applied to determine whether air pollution data could predict the daily hospital admissions for the upcoming day.Results: A total of 10,876 inpatients with respiratory diseases were included between January 1, 2009 and December 31, 2016. The CCA showed significant correlations between air pollution and daily hospital admissions (r = 0.3564, p < 0.001), the duration of hospitalization (r = 0.2911, p < 0.001) and the economic cost of hospitalization (r = 0.2933, p < 0.001) for respiratory disease. PM10 contributed most to daily hospital admissions for respiratory disease; the concentration the day before hospitalization contributed most to the daily hospital admissions for respiratory disease. There was a slightly stronger correlation between air pollution and respiratory disease in children aged 2–18 years (R = 0.36 vs. R = 0.31 in those under 2 years old). No significant difference was found between male and female patients. The prediction analysis showed that air pollution could successfully predict daily pediatric inpatient hospital admissions (R = 0.378, permutation p < 0.001).Conclusions: Air pollution was significantly associated with hospital admissions, hospitalization duration and the economic cost of hospitalization in children with respiratory diseases. The maximum effect occurred on the day before hospitalization. The effect of PM10 on daily pediatric inpatient hospital admissions for respiratory disease was the greatest among the pollutants evaluated.
Background Unprecedented durable responses are identified in clinical studies to target the signaling of programmed cell death protein-1 (PD-1) as well as its ligand (PD-L1) in patients with squamous-cell non-small cell lung cancer (NSCLC). However, factors predicting the patient subtypes that are responsive to PD-1/PD-L1inhibitors have not been fully understood yet. Biomarkers, like PD-L1 expression, tumor mutational burden(TMB), DNA mismatch repair deficiency (dMMR), and tumor-infiltrating lymphocytes (TILs), have been utilized to select patients responsive to PD-1/PD-L1inhibitors in the clinic, but each of them has limited use. Lung adenocarcinoma patients with a mutation of TP53 or KRAS, particularly those with co-mutations of TP53 and KRAS, can benefit from anti–PD-1 treatment. Case presentation In this study, the co-mutations of TP53 and KRAS in a 64-year-old non-smoking man with squamous-cell NSCLC patient was described using the next-generation sequencing (NGS) technology. The patient was treated with the pembrolizumab combined with gemcitabine as the salvage therapy, and a marked partial response could be attained, which had persisted for over 7 months. Conclusion In addition to testing common driving genes, like EGFR, ALK, ROS1 and BRAF, both TP53, and KRAS should also be considered in advanced or metastatic squamous-cell NSCLC.TP53 and KRAS co-mutations in squamous-cell NSCLC can be a potential factor to assess possible response to PD-1 blockade immunotherapy, but further studies with more cases are needed to confirm the prediction power.
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