Prognostic Nomogram and Therapeutic Option of Cancer-Specific Death in the Patients with Metachronous Second Primary Lung Cancer.

With the increase of long-term primary lung cancer survivors, studies focused on metachronous second primary lung cancer (SPLC) have become very urgent. This study aimed to develop a prognostic nomogram and determine therapeutic options of cancer-specific death for patients with metachronous SPLC with and without the competing risk of other-specific death. Study population came from the SEER-18 database between 2006 and 2016. According to the clinical practice guideline of SPLC, the interval time of IPLC and metachronous SPLC was set to 4 years. We constructed nomograms with Lasso + Cox regression model and competing risk model to predict the prognosis and identify therapeutic options of metachronous SPLC patients with the assessment of model performance by the C-index, calibration plot, and decision curve analysis. In addition, two subgroup analyses stratified by histology and tumor size were used to better select therapeutic options for a certain population. 1300 patients with metachronous SPLC were incorporated in this study with 50.1% of the 5-year cumulative incidence in cancer-specific death. Compared with Lasso + Cox regression analysis, competing risk analysis harbored a higher C-index (0.811 vs. 0.76) and better net benefit in predicting cancer-specific death of metachronous SPLC. Two statistical analyses suggested that surgery alone was a preferentially therapeutic option of metachronous SPLC, whereas the effect of surgery + radiation in treating metachronous SPLC was similar to radiation alone. Subgroup analyses indicated that patients with metachronous SPLC were considered receiving different therapeutic options in different histology and tumor size but preferred to receive surgical treatment as the first choice. For primary lung cancer survivors, aggressive surgical treatment was the first-line selection of metachronous SPLC, followed by radiation alone, surgery + radiation, and no surgery + radiation.

Circ-PGC increases the expression of FOXR2 by targeting miR-532-3p to promote the development of non-small cell lung cancer.

This study was to explore the function of circular progastricsin (circ-PGC) in NSCLC. The histological morphology of tumor tissues was observed by hematoxylin and eosin (HE) staining. The expression of circ-PGC, miR-532-3p and forkhead box R2 (FOXR2) mRNA was measured by real-time quantitative polymerase chain reaction (RT-qPCR). The protein level of FOXR2 was checked by western blot. In functional analyses, cell viability, colony formation, cell apoptosis, cell migration and cell invasion were investigated using cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry assay, wound healing assay and transwell assay. Besides, glycolysis metabolism was assessed by the levels of glucose consumption, lactate production and adenosine triphosphate (ATP) production. The predicted relationship between miR-532-3p and circ-PGC and FOXR2 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The results showed that circ-PGC and FOXR2 were upregulated in NSCLC tissues and cells. Circ-PGC knockdown or FOXR2 knockdown inhibited NSCLC cell viability, colony formation, cell migration, invasion and glycolysis metabolism, and FOXR2 overexpression rescued these inhibitory effects caused by circ-PGC knockdown. MiR-532-3p harbored the same binding site with circ-PGC and FOXR2, and circ-PGC positively regulated FOXR2 expression by targeting miR-532-3p. The expression of ß-catenin and c-Myc was decreased in cells after circ-PGC knockdown but recovered with miR-532-3p inhibition or FOXR2 overexpression. Circ-PGC downregulation also inhibited tumor growth in vivo. In conclusion, circ-PGC positively regulated FOXR2 expression by competitively binding to miR-532-3p, thereby promoting the development of NSCLC, and the Wnt/ß-catenin signaling pathway might be activated by the circ-PGC/miR-532-3p/FOXR2 network.

Statin use and prognosis of lung cancer: a systematic review and meta-analysis of observational studies and randomized controlled trials.

BACKGROUND: Previous clinical studies reported inconsistent results on the associations of statins with the mortality and survival of lung cancer patients. This review and meta-analysis summarized the impact of statins on mortality and survival of lung cancer patients. MATERIALS AND METHODS: Eligible papers of this meta-analysis were searched by using PubMed, EMBASE, and Cochrane until July 2017. Primary end points were the mortality (all-cause mortality and cancer-specific mortality) and survival (progression-free survival and overall survival) of patients with statin use. Secondary end points were overall response rate and safety. The random-effects model was used to calculate pooled HRs and 95% CIs. RESULTS: Seventeen studies involving 98,445 patients were included in the meta-analysis. In observational studies, the pooled HR indicated that statins potentially decreased the cancer-specific mortality and promoted the overall survival of lung cancer patients. Statins showed an association with decreased all-cause mortality in cohort studies (HR =0.77, 95% CI: 0.59-0.99), but not in case-control studies (HR =0.75, 95% CI: 0.50-1.10). However, statin use showed no impact on mortality and overall survival in randomized controlled trials. Meanwhile, this meta-analysis indicated that statin use did not affect the progression-free survival of lung cancer patients in observational studies and randomized controlled trials. In addition, statins potentially enhanced the effects of tyrosine kinase inhibitors (HR=0.86, 95% CI: 0.76-0.98) and chemotherapy (HR=0.86, 95% CI: 0.81-0.91) on the overall survival of patients with non-small-cell lung cancer, but did not increase overall response rate and toxicity. CONCLUSION: Statins were potentially associated with the decreasing risk of mortality and the improvement of overall survival in observational studies but not in randomized controlled trials.

miR302a inhibits the proliferation of esophageal cancer cells through the MAPK and PI3K/Akt signaling pathways.

MicroRNAs (miRNAs/miRs) are involved in the regulation of various types of cancer, either as oncogenes or tumor suppressors. miR302a has been reported that it could suppress tumor cell proliferation by inhibiting Akt in prostate cancer. The present study examined the effect of miR302a on proliferation and invasion in esophageal cancer cell lines. The expression levels of miR302a in esophageal cancer cell lines was determined by reverse transcription-polymerase chain reaction. Subsequently, miR302a mimics were transfected into esophageal cancer cells, and cell viability and invasion were assessed by MTT and Transwell assays. In addition, the effects of miR302a on the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathways were investigated by western blot analysis. The results revealed that miR302a expression was significantly decreased in the esophageal cancer cell lines compared with a healthy esophagus epithelium cell line. Upregulation of miR302a inhibited the proliferation and invasion of esophageal cancer cells, and decreased the phosphorylation of extracellular signal-regulated kinase 1/2 and Akt. Taken together, the results of the present study indicated that miR302a overexpression inhibited the proliferation and invasion of esophageal cancer cells through suppression of the MAPK and PI3K/Akt signaling pathways, indicating the potential value of miR302a as a treatment target for human esophageal cancer.

MicroRNA-181b is downregulated in non-small cell lung cancer and inhibits cell motility by directly targeting HMGB1.

The expression of microRNA-181b (miR-181b) has been investigated in various human cancers. However, the expression and functions of miR-181b in non-small cell lung cancer (NSCLC) are yet to be studied. In the present study, miR-181b expression in NSCLC tissues and cell lines was analyzed by quantitative polymerase chain reaction, and was shown to be recurrently downregulated. Following transfection of the H23 and H522 NSCLC cells lines with miR-181b, cell migration and cell invasion assays were performed to evaluate the effect of miR-181b overexpression on the cell motility. It was demonstrated that overexpression of miR-181b inhibited the migration and invasion of NSCLC cells. Subsequently, bioinformatics analysis, western blotting and luciferase reporter assays were conducted to investigate the mechanism underlying the miR-181b-mediated inhibition of NSCLC cell motility. It was found that miR-181b directly targeted high-mobility group box-1 (HMGB1) in NSCLC cells. These results reveal a novel therapeutic target, the miR-181b/HMGB1 axis, in NSCLC. Treatment approaches targeting this axis will be beneficial to prevent NSCLC from becoming invasive.

[Risk factors of mortality in severe chest trauma patients].

OBJECTIVE: To investigate the risk factors of mortality in patients with severe chest trauma (SCT). METHODS: The clinical data of 777 SCT [abbreviated injury scale (AIS) ≥3] patients who were treated in the Chongqing Emergency Medical Center from January 2006 to April 2009 were retrospectively reviewed. Stepwise logistic regression analysis was used to explore 15 possible mortality-related risk factors. RESULTS: Seven factors were found to be correlated with the mortality of SCT: age, hemorrhagic shock, multiple organ dysfunction syndrome (MODS), pulmonary infection, abdominal organ injury, Glasgow coma scale (GCS) score, and thorax AIS score. Among them five factors were the independent factors that might increase the mortality of SCT: hemorrhagic shock (B=1.710, OR=1.291, P=0.001), MODS (B=3.453, OR=1.028, P<0.001), pulmonary infection (B=2.396, OR=10.941, P<0.001), abdominal organ injury (B=1.542, OR=1.210, P=0.005), and thorax AIS score ≥4 (B=0.487, OR=1.622, P<0.001). Two factors showed protective effects: age ≤60 years (B=-0.035, OR=0.962, P=0.01) and GCS score ≥12 (B=-0.635, OR=0.320, P<0.001). CONCLUSIONS: Age, disease severity, and complications (hemorrhagic shock, MODS, and pulmonary infection) are independent risk factors of the mortality of SCT. Effective treatment programs targeting these risk factors may improve the outcomes of SCT patients.

[Prevalence and mortality of severe chest trauma in Three Gorges Area of China].

OBJECTIVE: To analyze the epidemiological features of severe chest trauma (SCT) and investigate the risk factor of its mortality in the Three Gorges Area of China. METHODS: The clinical data of 1834 SCT patients who were admitted in three hospitals in this area from January 1990 to December 2009 were retrospectively reviewed. Th epidemiological features of SCT were analyzed using a database. Stepwise logistic regression analysis was used to analyze 15 possible risk factors affecting mortality. RESULTS: The morbidity rates of blunt trauma (68.5% vs. 74.7%,p=0.006) and sharp instrument injury (12.2% vs. 15.9%,p=0.039) showed significant differences before and after 2000. The pre-hospital time [(3.45±2.38)h vs. (2.20±4.39)h,p<0.01] and transfer rate (32.39% vs. 36.80%,p=0.01) significantly improved. The thoracic Abbreviated Injury Scale (AIS)(3.56±0.71vs. 3.43±0.58,p<0.01)score and Revised Trauma Score (RTS)(7.14±2.18 vs. 6.93±1.07,p<0.01) significantly increased. Treatment for pulmonary infection (12.63±4.79 vs. 17.16±6.41,p=0.019) and hemorrhagic shock (2.4±0.75 vs. 3.4±1.34,p=0.008 )was significantly improved. The leading cause of death was hypovolemic shock (59.41%). The independent rik factors of death among these SCT patients included: hemorrhagic shock (B=1.710,OR=1.291,p=0.001), multiple organ dysfunction syndrome (B=3.453,OR=1.028,p<0.001), pulmonary infection(B=2.396,OR=10.941,p<0.001), abdominal organ injury(B=1.542,OR=1.210,p=0.005), and thorax AIS(B=0.487,OR=1.622,p<0.001). CONCLUSIONS: The prevalence of SCT shows an increasing trend in the Three Gorges Area in recent years, but with a decreased rate of complications and improved treatment. Age, complications, thorax AIS, and GCS are useful prognostic indicators.

[Association between the polymorphisms of cluster of differentiation 14 gene promoters and the susceptibility of multiple organ dysfunction syndrome after severe chest trauma].

OBJECTIVE: To investigate the polymorphisms of cluster of differentiation 14(CD14)gene promoters and explore whether such polymorphisms are associated with the susceptibility to multiple organ dysfunction syndrome(MODS) in Chongqing population. METHODS: The single nucleotide polymorphisms of the promoter region of CD14 gene at position -1145 and -159 were detected using polymerase chain reaction-restriction fragment length polymorphism method in 106 patients with severe chest trauma, among whom 47 were with MODS. RESULTS: Trauma patients carrying G allele tended to have a higher risk of MODS than those carrying A allele at position-1145, the MODS scores in trauma patients carrying G allele were significantly higher than those carrying A allele (P=0.217 for dominant effect and P=0.037 for recessive effect), and the MODS scores in trauma patients carrying T allele were significantly higher than those carrying C allele at position -159 (P=0.048 for dominant effect and P=0.198 for recessive effect). The genotypes of CD14 gene at positions -1145 and -159 were significantly correlated with the MODS scores (P=0.043,P=0.046). Compare with single-point mutation, simultaneous two-point mutation had significantly higher risk of MODS (Pü0.01), while the difference of MODS scores showed no statistical significance (P=0.239). CONCLUSION: The polymorphisms of CD14 gene promoters are associated with MODS after severe chest trauma in Chongqing population.