This meta-analysis examines whether differences in biomarkers, such as programmed cell death ligand 1 (PD-L1) expression and tumor mutation burden, are associated with improved response to immunotherapy and survival in patients with advanced non–small cell lung cancer (NSCLC).

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KRAS is an independent prognostic marker in resected stage I lung adenocarcinoma. Differential outcomes are associated with codon and amino acid specific KRAS mutations.

AimsEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown dramatic clinical benefits in advanced non-small cell lung cancer (NSCLC); however, resistance remains a serious problem in clinical practice. The present study analyzed mTOR-associated signaling-pathway differences between the EGFR TKI-sensitive and -resistant NSCLC cell lines and investigated the feasibility of targeting mTOR with specific mTOR inhibitor in EGFR TKI resistant NSCLC cells.MethodsWe selected four different types of EGFR TKI-sensitive and -resistant NSCLC cells: PC9, PC9GR, H1650 and H1975 cells as models to detect mTOR-associated signaling-pathway differences by western blot and Immunoprecipitation and evaluated the antiproliferative effect and cell cycle arrest of ku-0063794 by MTT method and flow cytometry.ResultsIn the present study, we observed that mTORC2-associated Akt ser473-FOXO1 signaling pathway in a basal state was highly activated in resistant cells. In vitro mTORC1 and mTORC2 kinase activities assays showed that EGFR TKI-resistant NSCLC cell lines had higher mTORC2 kinase activity, whereas sensitive cells had higher mTORC1 kinase activity in the basal state. The ATP-competitive mTOR inhibitor ku-0063794 showed dramatic antiproliferative effects and G1-cell cycle arrest in both sensitive and resistant cells. Ku-0063794 at the IC50 concentration effectively inhibited both mTOR and p70S6K phosphorylation levels; the latter is an mTORC1 substrate and did not upregulate Akt ser473 phosphorylation which would be induced by rapamycin and resulted in partial inhibition of FOXO1 phosphorylation. We also observed that EGFR TKI-sensitive and -resistant clinical NSCLC tumor specimens had higher total and phosphorylated p70S6K expression levels.ConclusionOur results indicate mTORC2-associated signaling-pathway was hyperactivated in EGFR TKI-resistant cells and targeting mTOR with specific mTOR inhibitors is likely a good strategy for patients with EGFR mutant NSCLC who develop EGFR TKI resistance; the potential specific roles of mTORC2 in EGFR TKI-resistant NSCLC cells were still unknown and should be further investigated.

Sex-determining region Y-box 9 (SOX9), a vital transcription factor, play important roles in numerous biological and pathological processes. However, the clinical significance and biological role of SOX9 expression has not been characterized in human esophageal squamous cell cancer (ESCC). Herein, we found that SOX9 was markedly upregulated, at both mRNA and protein level, in ESCC cell lines and ESCC tissues and that SOX9 expression was significantly correlated with tumor clinical stage, T classification, N classification, M classification, pathological differentiation, and shorter overall survival. The proliferation and tumorigenicity of ESCC cells were dramatically induced by SOX9 overexpression but were inhibited by SOX9 knockdown both in vitro and in vivo. Moreover, we demonstrated that upregulation of SOX9 increased the expression of phosphorylated Akt, the cyclin-dependent kinase (CDK) regulator cyclin D1, phosphorylated forkhead box O (FOXO)1, and phosphorylated FOXO3, but SOX9 downregulation decreased their expression, whereas the levels of the CDK inhibitors p21Cip1 and p27Kip1 were attenuated in SOX9-transduced cells. Taken together, our results suggest that SOX9 plays an important role in promoting the proliferation and tumorigenesis of ESCC and may represent a novel prognostic marker for the disease.

BackgroundThis study investigated the incidence, imaging characteristics and mechanical factors in scoliotic patients with pectus excavatum.MethodsA total of 142 scoliostic patients with pectus excavatum were evaluated prior to operation. The evaluation included a complete physical exam, phenotype and severity of the pectus excavatum, incidence and severity of scoliosis, and analysis of radiological images, including calculation of the Haller index.ResultsTwenty five out of 142 patients (17.61%) with pectus excavatum had scoliosis with a Cobb angle >10 degrees, and in 80.00% of the cases the spinal column was bent to the right. Seventeen patients had bent-to-the-right spines that involved the 6th to 10 th thoracic vertebrae. We found that 23 out of 25 patients with a Cobb angle more than 10° were teenagers and adults. The incidence of scoliosis was only 6.06% in the children under 11 years whereas it was 21.79% in the teenage group.ConclusionsMechanical forces appear to play a role in the coexistence of pectus excavatum and scoliosis. There is a relationship between age, severity (Haller index), asymmetry and scoliosis. The heart and mediastinum play a role in providing an outward force to the left of the sternum which may be an important reason for the coexistence of pectus excavatum and scoliosis, but the correlation needs further proof.

Sampling greater than 3 LNS and greater than 10 RNs was associated with an increase in nodal upstaging. Only LNS greater than 3 was found to be an independent predictor of mortality in VATS lobectomy and segmentectomy in clinical early-stage NSCLC.

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