Predicting the risk of lung cancer using machine learning: A large study based on UK Biobank.

In response to the high incidence and poor prognosis of lung cancer, this study tends to develop a generalizable lung-cancer prediction model by using machine learning to define high-risk groups and realize the early identification and prevention of lung cancer. We included 467,888 participants from UK Biobank, using lung cancer incidence as an outcome variable, including 49 previously known high-risk factors and less studied or unstudied predictors. We developed multivariate prediction models using multiple machine learning models, namely logistic regression, naïve Bayes, random forest, and extreme gradient boosting models. The performance of the models was evaluated by calculating the areas under their receiver operating characteristic curves, Brier loss, log loss, precision, recall, and F1 scores. The Shapley additive explanations interpreter was used to visualize the models. Three were ultimately 4299 cases of lung cancer that were diagnosed in our sample. The model containing all the predictors had good predictive power, and the extreme gradient boosting model had the best performance with an area under curve of 0.998. New important predictive factors for lung cancer were also identified, namely hip circumference, waist circumference, number of cigarettes previously smoked daily, neuroticism score, age, and forced expiratory volume in 1 second. The predictive model established by incorporating novel predictive factors can be of value in the early identification of lung cancer. It may be helpful in stratifying individuals and selecting those at higher risk for inclusion in screening programs.

Manipulation of Shallow-Trap States in Halide Double Perovskite Enables Real-Time Radiation Dosimetry.

Storage phosphors displaying defect emissions are indispensable in technologically advanced radiation dosimeters. The current dosimeter is limited to the passive detection mode, where ionizing radiation-induced deep-trap defects must be activated by external stimulation such as light or heat. Herein, we designed a new type of shallow-trap storage phosphor by controlling the dopant amounts of Ag+ and Bi3+ in the host lattice of Cs2NaInCl6. A distinct phenomenon of X-ray-induced emission (XIE) is observed for the first time in an intrinsically nonemissive perovskite. The intensity of XIE exhibits a quantitative relationship with the accumulated dose, enabling a real-time radiation dosimeter. Thermoluminescence and in situ X-ray photoelectron spectroscopy verify that the emission originates from the radiative recombination of electrons and holes associated with X-ray-induced traps. Theoretical calculations reveal the evolution process of Cl-Cl dimers serving as hole trap states. Analysis of temperature-dependent radioluminescence spectra provides evidence that the intrinsic electron-phonon interaction in 0.005 Ag+@ Cs2NaInCl6 is significantly reduced under X-ray irradiation. Moreover, 0.025 Bi3+@ Cs2NaInCl6 shows an elevated sensitivity to the accumulated dose with a broad response range from 0.08 to 45.05 Gy. This work discloses defect manipulation in halide double perovskites, giving rise to distinct shallow-trap storage phosphors that bridge traditional deep-trap storage phosphors and scintillators and enabling a brand-new type of material for real-time radiation dosimetry.

Circ-PGAM1 Enhances Matrine Resistance of Non-Small Cell Lung Cancer via the miR-326/CXCR5 Axis.

Background: Circular RNAs (circ-RNAs) have been demonstrated to influence initiation, drug resistance, and metastasis of tumors. However, the effects of circular-phosphoglycerate mutase 1 (circ-PGAM1) on matrine resistance in nonsmall cell lung cancer (NSCLC) remain unknown. Materials and Methods: The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine gene expression. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and cell colony formation assays were used to evaluate NSCLC apoptosis and cell proliferation after indicated treatments, respectively. Results: circ-PGAM1 was upregulated in human NSCLC cell lines (H1299 and A549) compared with the human normal lung epithelial (BEAS-2B) cells. circ-PGAM1 overexpression reversed the matrine treatment-induced inhibition on proliferation of NSCLC cells (A549 and H1299) and rescued the matrine treatment-stimulated apoptosis of these cells. miR-326 was demonstrated to interact with circ-PGAM1. circ-PGAM1 knockdown enhanced the antitumor effect of matrine on NSCLC cell proliferation and apoptosis, which was reversed by miR-326 inhibition. The authors also identified CXCR5 as a key downstream target of miR-326 in A549 cells. Conclusions: circ-PGAM1 enhances matrine resistance of NSCLC cells through the miR-326/CXCR5 axis. The authors' findings provide new insights into NSCLC-targeted therapy.

Research progress on the relationship between the TOR signaling pathway regulator, epigenetics, and tumor development.

Almost all cellular activities depend on protein folding, signaling complex assembly/disassembly, and epigenetic regulation. One of the most important regulatory mechanisms responsible for controlling these cellular processes is dynamic protein phosphorylation/dephosphorylation. Alterations in phosphorylation networks have major consequences in the form of disorders, including cancer. Many signaling cascades, including the target of rapamycin (TOR) signaling, are important participants in the cell cycle, and dysregulation in their phosphorylation/dephosphorylation status has been linked to malignancies. As a TOR signaling regulator, protein phosphatase 2A (PP2A) is responsible for most of the phosphatase activities inside the cells. On the other hand, TOR signaling pathway regulator (TIPRL) is an essential PP2A inhibitory protein. Many other physiological roles have also been suggested for TIPRL, such as modulation of TOR pathways, apoptosis, and cell proliferation. It is also reported that TIPRL was increased in various carcinomas, including non-small-cell lung carcinoma (NSCLC) and hepatocellular carcinomas (HCC). Considering the function of PP2A as a tumor suppressor and also the effect of the TIPRL/PP2A axis on apoptosis and proliferation of cancer cells, this review aims to provide a complete view of the role of TIPRL in cancer development in addition to describing TIPRL/PP2A axis and its epigenetic regulation.

Concordance Study of a 520-Gene Next-Generation Sequencing-Based Genomic Profiling Assay of Tissue and Plasma Samples.

INTRODUCTION: Next-generation sequencing (NGS) enables simultaneous detection of actionable somatic variants and estimation of genomic signatures such as tumor mutational burden (TMB) or microsatellite instability (MSI) status, which empowers therapeutic decisions in clinical oncology. OBJECTIVE: Our retrospective study investigated the clinical performance of somatic variant detection in paired tissue and blood samples using a large targeted gene panel, the OncoScreen Plus, which interrogates 520 cancer-related genes. METHODS: We analyzed sequencing data derived from paired tissue and blood samples of 3005 patients spanning 20 solid tumor types, including lung (n = 1971), gastrointestinal (n = 625), breast (n = 120) and gynecological (n = 110), genitourinary (n = 38), and other cancers (n = 141). RESULTS: Across tumor types, the OncoScreen Plus panel achieved a high tissue detection rate, with an average of 97.9%. The average plasma detection rate was 72.2%, with an average tissue concordance rate of 36.6%. Considering all variant types, the plasma assay yielded an average sensitivity/true positive rate of 45.7%, with a positive predictive value of 64.7% relative to tissue assay. Pearson correlation analysis revealed a strong correlation in TMB estimated from blood and tissue samples (correlation coefficient 0.845, R2 = 0.756). MSI-high status was identified in five tumor types, including endometrial cancer (28.6%), colorectal cancer (2.5%), ovarian cancer (2.0%), gastric cancer (1.5%), and lung adenocarcinoma (0.2%). CONCLUSION: Paired tumor and blood samples from a large cohort of patients spanning 20 tumor types demonstrated that the OncoScreen Plus is a reliable pan-cancer panel for the accurate detection of somatic variants and genomic signatures that could guide individualized treatment strategies to improve the care of patients with advanced cancer.

A patient with metastatic non-small cell lung cancer who received pembrolizumab monotherapy after stereotactic body radiotherapy had progression-free survival of nearly 5 years: a case report.

Lung cancer is a malignancy with the highest morbidity and mortality in the world. Radiotherapy, chemotherapy, targeted therapy, and immunotherapy have been widely used to treat metastatic non-small cell lung cancer (NSCLC). Stereotactic body radiotherapy (SBRT), also known as stereotactic ablation radiotherapy (SABR), can precisely deliver a high dose of radiation to a target in a limited area. SBRT has been established as the standard treatment for patients with early NSCLC who are unsuitable for operation or refuse surgery and patients with oligometastatic NSCLC who are not suitable for surgery. As an immunologic agent, pembrolizumab has been approved to treat metastatic NSCLC in certain countries, including China and the United States. Increased tumor proportion score (TPS) can reduce pembrolizumab's immunotherapeutic effect, while SBRT can reduce TPS and enhance immunotherapy efficacy. However, there have been no reports in China on metastatic NSCLC patients who have received pembrolizumab monotherapy after stereotactic body radiotherapy (SBRT). Here, we present a case of progression-free survival (PFS) of nearly 5 years with pembrolizumab monotherapy after SBRT for metastatic NSCLC. This case is the patient with the most prolonged medication duration and who experienced the most efficacious treatment among the patients with metastatic NSCLC reported in the Chinese literature.

Downregulated Expression of linc-ROR in Gastric Cancer and Its Potential Diagnostic and Prognosis Value.

BACKGROUND: Gastric cancer (GC) is one of the global mortality diseases and has a poor prognosis due to the lack of ideal tumor biomarkers. Numerous studies have shown that long noncoding RNAs (lncRNAs) can affect the occurrence and development of cancer through a variety of signaling pathways. The abnormal expression and specificity of lncRNAs in tumors make them potential biomarkers of cancers. Nevertheless, the diagnostic roles of lncRNAs in GC have been poorly understood. So this study focuses on the clinical diagnostic value of lncRNAs in GC. MATERIALS AND METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to investigate the expression of the linc-ROR (long intergenic noncoding RNA, regulator of reprogramming) in 105 paired GC tissues and adjacent normal tissues. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were established to assess the diagnostic value of linc-ROR. The relationship between expression of linc-ROR and clinicopathological factors of patients with GC was further explored. Kaplan-Meier analysis was performed to evaluate the prognostic value of linc-ROR expression. RESULTS: The linc-ROR expression level was significantly decreased in GC tissues compared with its adjacent nontumor tissues (n = 105, P < 0.001). We also discovered that linc-ROR was evidently downregulated in 68.6% (72/105) of GC tissues. The AUC's value of linc-ROR was up to 0.6495, with sensitivity and specificity of 0.7524 and 0.5143, respectively. Intriguingly, the linc-ROR expression levels were obviously associated with tumor differentiation (P = 0.004). Notably, the overall survival rate of GC patients with high expression of linc-ROR was significantly higher than those with low expression. CONCLUSION: Our data revealed that linc-ROR has clinical potential as a biomarker for the diagnosis of GC and assessment of its prognosis.

Reduced expression of circRNA hsa_circ_0067582 in human gastric cancer and its potential diagnostic values.

BACKGROUND: Gastric cancer (GC) is one of the global mortality diseases and has a poor prognosis due to the lack of ideal tumor biomarkers. Circular RNAs (circRNAs) are an abundant kind of endogenous RNAs that recently are found play a crucial role in the cancer occurrence and development. Nevertheless, little is known with regard to the diagnostic values of these circRNAs for GC. In this article of research, we investigated the role of hsa_circ_0067582 in clinical diagnosis of GC. MATERIALS AND METHODS: We used divergent primers, and the expression levels of hsa_circ_0067582 in 93 fresh GC tissues and paired adjacent normal tissues from surgical patients were detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Then, a receiver operating characteristic (ROC) curve was established to assess the diagnostic significance of hsa_circ_0067582. The relationship between expression of hsa_circ_0067582 and clinicopathological factors of patients was made further explored. RESULTS: Hsa_circ_0067582 levels were significantly decreased in GC tissues contrasted with adjacent normal tissues (n = 93, P < .001). After that, we discovered that it was evidently downregulated in 81.7% (76/93) GC tissues. The area under the ROC curve (AUC) of hsa_circ_0067582 was up to 0.6937, the sensitivity was 66.67%, and the specificity was 61.29%. Moreover, the hsa_circ_0067582 levels were obviously associated with tumor diameter (P = .002) and carbohydrate antigen 19-9 (CA19-9, P = .01). Meanwhile, after operation, low-level group of hsa_circ_0067582 of GC patients was associated with better prognosis. CONCLUSION: Our data imply that hsa_circ_000067582 may be a potential biomarker for GC diagnosis and prognosis evaluation.

Lobectomy with high-position single-intercostal two-port video-assisted thoracoscope for non-small cell lung cancer is a safe and effective surgical procedure.

BACKGROUND: High-position single-intercostal two-port video-assisted thoracic surgery (VATS) technique has been used for thoracic diseases. It can effectively avoid postoperative chronic pain compared with the traditional three-port VATS. This study aimed to evaluate the safety and efficacy of high-position single-intercostal two-port video-assisted thoracoscopic lobectomy. METHODS: From June 2014 to December 2018, a total of 474 patients in our hospital with non-small cell lung cancer (NSCLC) underwent lobectomy with a high-position single-intercostal two-port video-assisted thoracoscope. A retrospective study of these patients was conducted, and follow-up was performed to analyze the patients' 3- and 5-year survival rates. RESULTS: Of the total number of patients, 27.6%, 41.4%, and 31% underwent surgery between the third, fourth, and fifth intercostals, respectively. During the operation, 31 patients were converted to open surgery or three-port thoracoscopic surgery. The average surgical time was 160.9±44.9 min, the average postoperative hospital stay was 5.6±3.4 days, the incidence of postoperative complications was 7.2%, and the average number of lymph nodes resected was 13.6±5.3. The 3-year overall survival (OS) rate of IA1, IA2, IA3, IB, IIA, IIB and IIIA was 99.0%, 98.6%, 96.3%, 91.2%, 85.7%, 66.7%, and 60.8%, respectively. Meanwhile, the 5-year OS rate of IA1, IA2, IA3, IB, and IIIA was 99.0%, 94.5%, 87.5%, 85.5%, and 43.3%, respectively. CONCLUSIONS: Lobectomy with a high-position single-intercostal two-port video-assisted thoracoscope for NSCLC is a safe and effective surgical procedure.

Downregulated Expression of hsa_circ_0005556 in Gastric Cancer and Its Clinical Significance.

BACKGROUND: Gastric cancer (GC) has a poor prognosis due to the lack of ideal tumor markers. Circular RNAs (circRNAs) are a novel type of noncoding RNA related to the occurrence of GC. Among our research, we investigated the role of hsa_circ_0005556 in GC. MATERIALS AND METHODS: The expression of hsa_circ_0005556 of 100 paired GC tissues and adjacent normal tissues was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was established to evaluate the diagnostic value of hsa_circ_0005556. The correlation between the expression of hsa_circ_0005556 and corresponding clinicopathological characteristic was explored. RESULTS: hsa_circ_0005556 was significantly downregulated in GC tissues contrasted with adjacent normal tissues (n = 100, p < 0.001). The areas under the ROC curve (AUC) of hsa_circ_0005556 were up to 0.773, while 64% sensitivity and 82% specificity, respectively. Moreover, its expression levels were significantly associated with differentiation (p = 0.001), TNM stage (p = 0.013), and lymphatic metastasis (p = 0.039). GC patients of high hsa_circ_0005556 levels had a longer overall survival (OS) than those of the low group (p = 0.047). CONCLUSION: hsa_circ_0005556 is a potential biomarker for GC, which may guide judgment of the indication of endoscopic treatment for early gastric cancer (EGC).

Surface charge-reversible polyelectrolyte complex nanoparticles for hepatoma-targeting delivery of doxorubicin.

Polymeric nanoparticles are greatly advancing the field of nanomedicine due to their ability for targeted and controlled drug release. Here, monodisperse pH-responsive surface charge-reversible and hepatoma-targeting polyelectrolyte complex nanoparticles (GC/HA NPs) near 80 nm were prepared via the ionotropic gelification by simple and mild co-precipitation of galactosylated chitosan (GC) and hyaluronate (HA). Their surface charges could transfer from negative in neutral or basic media to positive in acidic media, indicating their potential application for delivering anti-tumor drugs in response to the extracellular pH of the tumor environment. The unique "electrostatic sponge" structure enhanced their drug-loading capacity and encapsulation efficiency towards the anti-cancer agent doxorubicin (DOX), as well as the pH-triggered controlled release. MTT assays and fluorescence microscopy analysis revealed that the DOX-loaded GC/HA NPs possessed the hepatoma-targeting capacity with favorable biocompatibility. These features make them advanced anti-cancer drug nanocarriers for intelligent drug delivery systems.

Functionalized graphene oxide nanoparticles for cancer cell-specific delivery of antitumor drug.

The unique reduction-triggered functional graphene oxide nanoparticles (GON) with well-defined size and uniform distribution were designed as an innovative drug delivery platform for cancer treatment for the first time, via the redox radical polymerization of methacrylic acid from the polyethylene glycol (PEG) modified GON (GON-PEG), following by cross-linking with cystamine. Thermogravimetric analysis demonstrates that the typical PMAA2-GON-PEG carriers contain about 16 wt % PEG segments and 33 wt % poly(methacrylic acid) (PMAA) brushes. PEG moieties are incorporated to make the drug delivery platforms stealthy during blood circulation. Notably, introducing the cross-linked PMAA brushes efficiently minimizes the premature release of doxorubicin (DOX) in the stimulated normal tissues, and accelerates DOX release in the stimulated tumor tissues through response to reduce agent. The carriers showed a 6-fold faster releasing rate at pH 5.0 in the presence of 10 mM glutathione (GSH) (stimulated tumor tissues) than at pH 7.4 with 10 µM GSH (stimulated normal tissues). In vitro cytotoxicity test also showed that the cross-linked PMAA2-GON-PEG (CPMAA2-GON-PEG) carriers had remarkable cytocompatibility, and that the DOX-loaded CPMAA2-GON-PEG had excellent killing capability to SiHa cells.