Prognostic Modeling of Lung Adenocarcinoma Based on Hypoxia and Ferroptosis-Related Genes.

Background: It is well known that hypoxia and ferroptosis are intimately connected with tumor development. The purpose of this investigation was to identify whether they have a prognostic signature. To this end, genes related to hypoxia and ferroptosis scores were investigated using bioinformatics analysis to stratify the risk of lung adenocarcinoma. Methods: Hypoxia and ferroptosis scores were estimated using The Cancer Genome Atlas (TCGA) database-derived cohort transcriptome profiles via the single sample gene set enrichment analysis (ssGSEA) algorithm. The candidate genes associated with hypoxia and ferroptosis scores were identified using weighted correlation network analysis (WGCNA) and differential expression analysis. The prognostic genes in this study were discovered using the Cox regression (CR) model in conjunction with the LASSO method, which was then utilized to create a prognostic signature. The efficacy, accuracy, and clinical value of the prognostic model were evaluated using an independent validation cohort, Receiver Operator Characteristic (ROC) curve, and nomogram. The analysis of function and immune cell infiltration was also carried out. Results: Here, we appraised 152 candidate genes expressed not the same, which were related to hypoxia and ferroptosis for prognostic modeling in The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) cohort, and these genes were further validated in the GSE31210 cohort. We found that the 14-gene-based prognostic model, utilizing MAPK4, TNS4, WFDC2, FSTL3, ITGA2, KLK11, PHLDB2, VGLL3, SNX30, KCNQ3, SMAD9, ANGPTL4, LAMA3, and STK32A, performed well in predicting the prognosis in lung adenocarcinoma. ROC and nomogram analyses showed that risk scores based on prognostic signatures provided desirable predictive accuracy and clinical utility. Moreover, gene set variance analysis showed differential enrichment of 33 hallmark gene sets between different risk groups. Additionally, our results indicated that a higher risk score will lead to more fibroblasts and activated CD4 T cells but fewer myeloid dendritic cells, endothelial cells, eosinophils, immature dendritic cells, and neutrophils. Conclusion: Our research found a 14-gene signature and established a nomogram that accurately predicted the prognosis in patients with lung adenocarcinoma. Clinical decision-making and therapeutic customization may benefit from these results, which may serve as a valuable reference in the future.

Cytoplasmic expression of G protein-coupled estrogen receptor 1 correlates with poor postoperative prognosis in non-small cell lung cancer.

Background: A hormonal role in the development of non-small cell lung cancer (NSCLC) has been well documented, and the classic estrogen receptors (ERs)-ERα and ERß have been extensively investigated over the past decade. The expression of ERß was found to be high and display biological activity in NSCLC, but anti-estrogen therapy targeting this receptor has shown limited efficacy for the disease. The third estrogen receptor, G protein-coupled estrogen receptor 1 (GPER1/GPR30), was recently found to be highly expressed in NSCLC. Herein, we aimed to investigate the expression profile of GPER1 and correlate it with clinicopathological factors as well as postoperative prognosis in NSCLC. Methods: We examined GPER1 and ERß expression using immunohistochemistry among 183 NSCLC cases, including 132 lung adenocarcinoma (LUAD) with identified epidermal growth factor receptor (EGFR) mutation status and 51 squamous cell carcinoma (SCC) patients. We then conducted correlation analysis between the expression of GPER1 and clinicopathological factors and patients' postoperative prognosis. Results: Positive expression of GPER1 was categorized into 2 main classes: nuclei-GPER1 (nGPER1) and concurrent nuclei-and cytoplasm-GPER1 (n/cGPER1), according to its subcellular localization. The LUAD with wild-type EGFR (wt-EGFR) had a higher frequency of n/cGPER1 (50%) but a lower frequency of nGPER1 (31%) when compared with those with mutated EGFR (n/cGPER1: 31%, nGPER1: 41%, respectively). The expression of GPER1, regardless of subcellular localization, was positively correlated with tumor stage and lymph node metastasis. The median recurrence-free survival (mRFS) and overall survival (OS) were significantly worse in participants with n/cGPER1 expression than in those with nGPER1 or without GPER1 expression. Conclusions: This study revealed that GPER1 is aberrantly highly expressed and presents a unique GPER1 expression profile in NSCLC. The n/cGPER1 expression was significantly associated with EGFR mutation status, tumor stage, lymph node metastasis, and poor postoperative prognosis in NSCLC.

Left lower lobectomy and systematic lymph node dissection by complete video-assisted thoracic surgery.

A 50-year-old female was administered with left lower lobe lesion for 10 days. A preoperative chest computed tomography (CT) revealed a mass in the left basilar segment of the lung, about 2.1 cm × 1.7 cm in size. Therefore, video-assisted thoracic surgery (VATS) left lower lobectomy was performed. The operation takes 60 minutes. During the operation, the estimated blood loss was 15 mL. The patient was discharged on postoperative day (POD) 6 with no complications. And the pathological results confirmed the diagnosis of adenocarcinoma with no lymph nodes metastasis.

1,1'-Bis(diisobutyl-phosphino)cobalto-cenium hexa-fluorido-phosphate.

In the title compound, [Co(C(13)H(22)P)(2)]PF(6), the Co(III) atom is sandwiched between two (diisobutyl-phosphino)cyclo-penta-dienenyl ligands. The two diisobutyl-phophine units are trans to each other with respect to the Co(III) metal center. The PF(6) (-) anion links the cobaltocenium cations via weak C-H⋯F hydrogen bonds into a chain running along the b axis. The chains are further linked by C-H⋯F hydrogen bonds, forming a layer extending parallel to the (10) plane.

[nm23-H1 gene inhibits lung cancer cell invasion through down-regulation of PKC signal pathway].

OBJECTIVE: To study the molecular mechanisms of nm23-H1 for regulating PKC signal pathway before and after transfection with nm23-H1 gene. METHODS: Using Western-blot, Boyden-chamber, MTT and laser scanning confocal microscopy (LSCM) techniques to detect the distribution of PKC in cytosol and plasma membrane, changes of invasion and proliferation activity, PKC translocation status and changes of intracellular Ca(2+) concentration among different human pulmonary carcinoma cells with transfected or untransfected nm23-H1 gene, and changes of the three cell lines after treatment with Calphostin C, a PKC inhibitor. RESULTS: (1) The expression of PKCalpha, PKCbeta II on L9981 and L9981-pLXSN cell membrane, which was in activated status, was remarkably higher than those in L9981-nm23-H1 cell line (P < 0.001). The expression of PKCalpha, PKCbeta II in cytosol in L9981 and L9981-pLXSN cell lines, which was in inactivated status, was lower than those in L9981-nm23-H1 cell line (P < 0.001). It means that the PKC signal pathway was activated in L9981 and L9981-pLXSN cell lines. (2) PKCalpha and PKCbeta II mainly located in nuclei and perinuclear area in L9981 and L9981-pLXSN cells, which were in active status, and the Ca(2+) concentration in these cells was obviously higher than that in L9981-nm23-H1 cell line (P < 0.01). In L9981-nm23-H1 cell line, which was transfected with nm23-H1 gene, PKCalpha and PKCbeta II mainly located in soluble cytosolic section, in an inactive status. (3) The invasion and proliferation ability of L9981 and L9981-pLXSN lung cancer cells was higher than that of L9981-nm23-H1 cell line (P < 0.001). There was no statistically significant difference between L9981 and L9981-pLXSN cell lines (P > 0.05). (4) After treated with PKC inhibitor Calphstin C, the expression of PKC and PKCbeta II in membrane in L9981 and L9981-pLXSN cell lines was down-regulated (P < 0.001), PKCalpha and PKCbeta II were mainly located in cytosolic area, mainly in an inactive status, and the Ca(2+) concentration was found to be decreased in all the three cell lines. The invasion and proliferation ability of the three lung cancer cell lines were obviously decreasing (P < 0.001). However, the invasion and proliferation ability of L9981-nm23-H1 lung cancer cell line was still lower than that of L9981 and L9981-pLXSN lung cancer cell lines (P < 0.001). There was also no significant difference between L9981 and L9981-pLXSN cell lines (P > 0.05). CONCLUSION: The results of this study suggest that nm23-H1 gene might inhibit the invasion and metastasis of lung cancer cells by down-regulating PKC signaling pathway. The Ca(2+) in cells might be involved in this process.