Selenium-binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non-small cell lung cancer.

BACKGROUND: Selenium is an essential trace element in the human body. In epidemiological and clinical studies, Se supplementation significantly reduced the incidence of lung cancer in individuals with low baseline Se levels. The significant action of selenium is based on the selenium-containing protein as a mediator. Of note, the previous studies reported that the expression of selenium-binding protein 1 (SELENBP1) was obviously decreased in many human cancer tissues including non-small cell lung cancer (NSCLC). However, its roles in the origin and development of NSCLC are still unclear. METHODS: The expression of SELENBP1 was measured by qRT-PCR, Western blotting and IHC in our collected clinical NSCLC tissues and cell lines. Next, the CCK-8, colony formation, wound-haeling, Millicell, Transwell, FCM assay, and in vivo xenograft model were performed to explore the function of SELENBP1 in NSCLC. The molecular mechanisms of SELENBP1 were investigated by Western blotting or IF assay. RESULTS: We further identified that the expression of SELENBP1 was significantly decreased in NSCLC tissues in TCGA database and 45 out of 59 collected clinical NSCLC tissues compared with adjacent nontumor tissues, as well as in four NSCLC cell lines compared with normal lung cells. Particularly, we unexpectedly discovered that SELENBP1 was obviously expressed in alveolar type 2 (AT-II) cells for the first time. Then, a series of in vitro experiments uncovered that overexpression of SELENBP1 inhibited the proliferation, migration, and invasion of NSCLC cells, and induced cell apoptosis. Moreover, overexpression of SELENBP1 also inhibited growth and induced apoptosis of NSCLC cells in vivo. Mechanistically, we demonstrated that overexpression of SELENBP1 inhibited the malignant characteristics of NSCLC cells in part via inactivating the PI3K/AKT/mTOR signal pathway. Meanwhile, we found that overexpression of SELENBP1 inducing the apoptosis of NSCLC cells was associated with the activation of caspase-3 signaling pathway under nonhigh level of oxidative stress, but overexpression of SELENBP1 facilitating the cell apoptosis might be related to its combining with GPX1 and colocalizing in the nucleus under high level of oxidative stress. CONCLUSIONS: Our findings highlighted that SELENBP1 was an important tumor suppressor during the origin and development of NSCLC. It may help to discover novel biomarkers or drug therapy targets for NSCLC.

What does radiomics do in PD-L1 blockade therapy of NSCLC patients?

With the in-depth understanding of programmed cell death 1 ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC), PD-L1 has become a vital immunotherapy target and a significant biomarker. The clinical utility of detecting PD-L1 by immunohistochemistry or next-generation sequencing has been written into guidelines. However, the application of these methods is limited in some circumstances where the biopsy size is small or not accessible, or a dynamic monitor is needed. Radiomics can noninvasively, in real-time, and quantitatively analyze medical images to reflect deeper information about diseases. Since radiomics was proposed in 2012, it has been widely used in disease diagnosis and differential diagnosis, tumor staging and grading, gene and protein phenotype prediction, treatment plan decision-making, efficacy evaluation, and prognosis prediction. To explore the feasibility of the clinical application of radiomics in predicting PD-L1 expression, immunotherapy response, and long-term prognosis, we comprehensively reviewed and summarized recently published works in NSCLC. In conclusion, radiomics is expected to be a companion to the whole immunotherapy process.

KRAS G12C mutations in Asia: a landscape analysis of 11,951 Chinese tumor samples.

BACKGROUND: Kirsten rat sarcoma vial oncogene (KRAS) is one of the most prevalent oncogenes in multiple cancer types, but the incidence is different between the Asian and non-Asian populations. The recent development of KRAS G12C targeting drug has shown great promise. It is thus important to understand the genomic landscape of KRAS G12C in a specific population. METHODS: Sequencing data of 11,951 tumor samples collected from 11/2016 to 7/2019 from multiple centres in China were analyzed for KRAS mutation status. Concomitant genomic aberrations were further analyzed in tumors with KRAS G12C mutations, which were sequenced with comprehensive cancer panel including over 450 cancer-related genes. Smoking status and its correlation with KRAS were analyzed in 2,235 lung cancer cases within this cohort. RESULTS: KRAS mutations were identified in 1978 (16.6%) patient samples. Specifically, KRAS G12C accounted for 14.5% (n=286) of all KRAS mutations. G12C was most commonly seen in lung cancer (4.3%), followed by colorectal cancer (2.5%) and biliary cancer (2.3%). Almost all patients (99.6%) with G12C mutations had concomitant genomic aberrations. These were most commonly associated with the RAS/RTK pathway including BRAF and PI3KCA mutations. Moreover, KRAS mutation was positively correlated with smoking status in lung adenocarcinomas. CONCLUSIONS: The overall incidence of KRAS G12C mutations remains low in the Chinese population. The most common tumor types harboring KRAS G12C mutations are in patients suffering from lung, colorectal and biliary cancers.

Efficacy of Transcutaneous Electronic Nerve Stimulation in Postoperative Analgesia After Pulmonary Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of the study was to identify the analgesic efficacy and safety of transcutaneous electronic nerve stimulation in postoperative pain after pulmonary surgery. DESIGN: Electronic databases (PubMed, Embase, Web of Science, and CENTRAL) were systematically searched from their inception to June 2019. The continuous variables were pooled as the weighted mean difference with correlated 95% confidence interval. Results were recognized as significant when a P value is less than 0.05. Subgroup analyses, sensitivity analyses, and quality assessment were performed. RESULTS: Altogether, 10 studies were included. The pooled results indicated that transcutaneous electronic nerve stimulation group conferred lower pain intensity score on the first postoperative day (weighted mean difference = -0.93, 95% confidence interval = -1.56 to -0.30, P = 0.004), postoperative day 2 (weighted mean difference = -1.00, 95% confidence interval = -1.64 to -0.35, P = 0.002), postoperative day 3 (weighted mean difference = -0.92, 95% confidence interval = -1.76 to -0.09, P = 0.03), postoperative day 4 (weighted mean difference = -0.90, 95% confidence interval = -1.24 to -0.56, P < 0.001), and postoperative day 5 (weighted mean difference = -1.39, 95% confidence interval = -2.20 to -0.57, P < 0.001) compared with the placebo transcutaneous electronic nerve stimulation group. No publication bias was found. No significant discovery was obtained in sensitivity analyses. CONCLUSIONS: Transcutaneous electronic nerve stimulation might be an effective supplementary analgesic regimen in multimodal analgesia to decrease pain intensity after pulmonary surgery.

ZNF32 contributes to the induction of multidrug resistance by regulating TGF-ß receptor 2 signaling in lung adenocarcinoma.

Multidrug resistance (MDR) is one of the most important contributors to the high mortality of cancer and remains a major concern. We previously found that zinc finger protein 32 (ZNF32), an important transcription factor associated with cancer in Homo sapiens, protects tumor cells against cell death induced by oxidative stress and other stimuli. We thus hypothesized that ZNF32 might enable the tolerance of cancer cells to anti-tumor drugs because higher ZNF32 expression has been found in cancer tissues and in drug-resistant lung adenocarcinoma (AC) cells. In this study, we found that ZNF32 is upregulated by Sp1 (specificity protein 1) in response to drug treatment and that ZNF32 promotes drug resistance and protects AC cells against cisplatin or gefitinib treatment. ZNF32 overexpression in AC cells conferred resistance to EGFR (epidermal growth factor receptor) inhibitors by enhancing MEK/ERK activation. Moreover, ZNF32 was found to directly bind to the TGF-ßR2 (transforming growth factor-beta receptor 2) promoter to promote its expression, and ZNF32-induced resistance was mediated by enhancing TGF-ßR2 expression and activating the TGF-ßR2/SMAD2 pathway. In both a mouse model and ex vivo cultured patient samples, a high level of ZNF32 expression was closely associated with worse overall survival and cisplatin resistance. ZNF32 appears to be a potential inducer of drug resistance that could increase the expression of the drug resistance-associated gene TGF-ßR2 and subsequently facilitate the induction of drug resistance during both conventional chemotherapy and novel target therapy. Thus, ZNF32-associated target therapy is a potential novel adjuvant therapy that might effectively prevent the occurrence of multidrug resistance (MDR) during chemotherapy and improve the survival of patients with AC.