Astrocytic P2X7 receptor in retrosplenial cortex drives electroacupuncture analgesia.

P2X7 receptor (P2X7R) has been found to contribute to the peripheral mechanism of acupuncture analgesia (AA). However, whether it plays an important role in central mechanism remains unknown. In this study, we aimed to reveal the role of astrocytic P2X7R in retrosplenial cortex (RSC) in AA and provide new evidence for underlying the central mechanism of AA. We applied the chemogenetic receptors hM3Dq to stimulate or hM4Di to inhibit astrocytes ligand clozapine-N-oxide (CNO) following injection of adeno-associated virus (AAV) into the bilateral RSC, or pharmacologically intervened in the activity of the purinergic receptor P2X7R. Current data indicated that chemogenetic inhibition of astrocytes or injection of P2X7R agonist Bz-ATP in the bilateral RSC significantly reverses the analgesic effect of electroacupuncture (EA) in formalin tests while the bilateral injection of the P2X7R antagonist A438079 alleviated formalin-induced nociceptive behavior. Additionally, chemogenetic suppression of astrocytic P2X7R by injection of AAV in the bilateral RSC decreased hind paw flinches induced by formalin in the mice. These findings indicate the participation of both astrocytes and P2X7R in the RSC in EA analgesic. Moreover, P2X7R on astrocytes in the RSC appears to play a critical role in the ability of EA to attenuate formalin-induced pain responses in mice.

LINC00313 suppresses autophagy and promotes stemness of nasopharyngeal carcinoma cells through PTBP1/STIM1 axis.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a kind of malignant head and neck tumor with high mortality. lncRNAs are valuable diagnostic biomarkers and therapeutic targets for various tumors. This study investigated the effects and mechanism of LINC00313 in nasopharyngeal carcinoma. METHODS: Cell Counting Kit-8 (CCK-8) and immunohistochemistry were used for assessing cell proliferation. The levels of autophagy-related proteins, and stem cell markers were detected. Immunofluorescence assay was used for LC3 detection. Methylated RNA Immunoprecipitation (meRIP) of LINC00313 in NPC cells was assessed. The localization of LINC00313 was verified by luorescence in situ hybridization (FIHS). The interaction between LINC00313 and the downstream targets were analyzed and confirmed by immunoprecipitation (RIP). Besides, the tumorigenesis roles of LINC00313 were confirmed in tumor growth mice model. RESULTS: LINC00313 was increased in NPC tissues and cells. LINC00313 knockdown enhanced autophagy, and decreased stemness and cell viability of NPC cells through regulating STIM1. METTL3/IGF2BP1-mediated m6A modification promoted the stabilization and up-regulation of LINC00313. LINC00313 activated AKT/mTOR pathway in NPC cells through PTBP1/STIM1 axis. Moreover, LINC00313 promoted tumor growth and metastasis in xenograft model. CONCLUSION: Upregulation of LINC00313 suppressed autophagy and promoted stemness of NPC cells through PTBP1/STIM1 axis.

CircLASP1 silence strengthens the therapeutic effects of MK-2206 on nasopharyngeal cancer through upregulating miR-625.

Therapeutic effects of MK-2206 are largely limited due to the complexity of the pathogenesis of nasopharyngeal cancer (NPC). Here, we aimed to investigate whether and how circLASP1 is involved in the therapeutic effects of MK-2206 on NPC. We showed circLASP1 was increased while miR-625 was decreased in NPC tissues and cell lines. CircLASP1 silence strengthened the therapeutic effects of MK-2206 via suppressing NPC cell proliferation and inducing autophagy and apoptosis in vitro. In mechanism analyses, we found that circLASP1 indirectly released AKT by directly binding to miR-625 in NPC cells, and miR-625 acted as a tumor suppressor in NPC and activated cell autophagy through inhibiting the AKT/mTOR pathway. Most importantly, knockdown of circLASP1 was revealed to enhance the therapeutic effects of MK-2206 on NPC in vivo. Our results suggest that the circLASP1/miR-625 axis is involved the therapeutic effects of MK-2206 on NPC by regulating autophagy, proliferation, and apoptosis through the AKT/mTOR pathway. miR-625 is involved in NPC tumorigenesis.

Novel solid acid catalyst for the production of 5-hydroxymethylfurfural with fructose dehydration.

BACKGROUND: 5-Hydroxymethylfurfural (5-HMF) is a high value-added platform compound which can be obtained by dehydration of hexose under acidic conditions. OBJECTIVE: In this paper, a novel impregnation strategy for the molecular sieves (ZSM-5) as carrier and phosphotungstic acid (TPA) as active ingredient is proposed, the influence of the fructose dehydration process were studied and eco-friendliness, low-cost 5-hydroxymethylfurfural (5-HMF) was successfully obtained. METHOD: The structure surface area, pore size, acidity and microstructure of solid acid catalysts were investigated by XRD, BET, NH3-TPD and SEM. The influences of reaction temperature, reaction time, catalyst dosage on the yield of 5-hydroxymethylfurfural (5-HFM) were investigated. RESULTS: The results showed that TPA/ZSM-5 (mass ratio 20:10) has good dispersion and catalytic activity, fructose dosage 5 g, reaction temperature 140 °C, reaction time 2 h, catalyst dosage 0.5 g, and the yield of 5-hydroxymethylfurfural was 80.75% and after five times use the yield of 5-HMF remained above 75%. CONCLUSION: The novel solid acid TPA/ZSM-5 catalyst exhibited good catalytic activity and stability for the fructose dehydration to produce 5-HMF.

Overexpression of p-4EBP1 associates with p-eIF4E and predicts poor prognosis for non-small cell lung cancer patients with resection.

Eukaryotic initiation factor 4E (eIF4E) and its phosphorylated form (p-eIF4E) play a crucial role in the protein synthesis, both are under regulation of eIF4E-binding protein 1 (4EBP1) and mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs). This study aims to explore the potential prognostic significance of p-4EBP1 and p-eIF4E in NSCLC patients. The expression of p-4EBP1 and p-eIF4E in NSCLC patients was detected by immunohistochemistry (IHC) staining in tissue microarrays (TMAs) containing 354 NSCLC and 53 non-cancerous lung tissues (Non-CLT). The overexpression percentage of p-4EBP1 and p-eIF4E in lung squamous cell carcinoma (SCC) and adenocarcinoma (ADC) was significantly higher than that of Non-CLT. P-4EBP1 expression in patients with advanced clinical stage was higher than that in early stage. Expression of p-4EBP1 had a positive relationship with p-eIF4E expression both in lung SCC and ADC. NSCLC patients with high expression of p-4EBP1 and p-eIF4E alone or in combination had a lower survival rate than that of other phenotypes. For NSCLC patients, p-4EBP1 is an independent poor prognostic factor as well as clinical stage, LNM and pathological grade. Overexpression of p-4EBP1 and p-eIF4E might be novel prognostic marker for NSCLC, who possesses potential application value for NSCLC targeted therapy.

Overexpressed p-S6 associates with lymph node metastasis and predicts poor prognosis in non-small cell lung cancer.

BACKGROUND: Ribosomal protein S6 (S6), a downstream effect media of the AKT/mTOR pathway, not only is a part of 40S small subunit of eukaryotic ribosome, but also involves in protein synthesis and cell proliferation during cancer development. METHODS: In present study, we explore the association between phosphorylated S6 (p-S6) protein expression and clinicopathological features as well as prognostic implications in NSCLC. P-S6 was detected in tissue microarrays (TMAs) containing 350 NSCLC, 53 non-cancerous lung tissues (Non-CLT), and 88 cases of matched metastatic lymph node lesions via immunohistochemistry (IHC). Transwell assays and wound healing assay were used to assess the effects of p-S6 inhibition on NSCLC cell metastasis. RESULTS: The p-S6 expression in NSCLC was more evident than that in Non-CLT (p < 0.05). Compared to NSCLC patients who have no lymph node metastasis (LNM), those with LNM had higher p-S6 expression (p = 0.001). Regardless of lung squamous cell carcinoma (SCC) or adenocarcinoma (ADC), p-S6 was increased obviously in metastatic lymph nodes compared with matched primary cancers (p = 0.001, p = 0.022, respectively). Inhibition of p-S6 decreased the metastasis ability of NSCLC cells. In addition, p-S6 was an independent predicted marker for LNM in patients with NSCLC (p < 0.001). According to survival analysis, patients with highly expressed p-S6 had a lower survival rate compared with that with lower expression (p = 0.013). P-S6 is an unfavorable independent prognostic factor for NSCLC patients (p = 0.011). CONCLUSION: Increased expression of p-S6 is not only a novel predictive biomarker of LNM but also poor prognosis in NSCLC.

Exosome-mediated miR-7-5p delivery enhances the anticancer effect of Everolimus via blocking MNK/eIF4E axis in non-small cell lung cancer.

Everolimus is a kind of mammalian target of rapamycin (mTOR) inhibitors. Activated mitogen-activated protein kinase interacting kinases/eukaryotic translation initiation factor 4E (MNK/eIF4E) axis plays a crucial role in resistance to Everolimus in non-small cell lung cancer (NSCLC). The eIF4E phosphorylation increased by mTOR inhibitors is mainly mediated by MNKs. However, the mechanisms are poorly understood. Recently, extensive reprogramming of miRNA profiles has also been found after long-term mTOR inhibitor exposure. Our previous studies have confirmed that tumor suppressor miR-7-5p is decreased in A549 cells after treatment with Everolimus. Exactly, MNK1 is the target of miR-7-5p. In this study, we investigated the biological functions and potential molecular mechanisms of miR-7-5p in the NSCLC undergoing treatment with Everolimus. We confirmed that Everolimus targeted mTORC1 inducing NSCLC cells to secrete miR-7-5p-loaded exosomes in Rab27A and Rab27B-dependent manners. Loss of intracellular miR-7-5p induced phosphorylation of MNK/eIF4E axis, but a supplement of extra exosomal miR-7-5p could reverse it. Of note, both low expression of miR-7-5p and elevated MNK1 protein were associated with a poor prognosis of NSCLC. Both endogenous miR-7-5p and exo-miR-7-5p enhanced the therapeutic efficacy of Everolimus by inhibiting the proliferation, migration, and metastasis of NSCLC in vitro and in vivo. The combination of miR-7-5p with Everolimus induced apoptosis to exhibit a synergistic anticancer therapeutic efficacy through dual abrogation of MNK/eIF4E and mTOR in NSCLC. In conclusion, Everolimus decreases the intracellular miR-7-5p by releasing of miR-7-5p loaded exosomes from NSCLC cells in Rab27A and Rab27B dependent manners. Either endogenous miR-7-5p or exo-miR-7-5p combined with Everolimus can enhance the anticancer efficacy by targeting MNK/eIF4E axis and mTOR. Besides, both low levels of miR-7-5p and positive expression of MNK1 act as independent poor prognostic biomarkers for NSCLC. Therefore, restoring miR-7-5p carried by exosome may be a promising novel combined therapeutic strategy with Everolimus for NSCLC.

Overexpression of P4HA1 associates with poor prognosis and promotes cell proliferation and metastasis of lung adenocarcinoma.

Prolyl 4-hydroxylase subunit alpha 1 (P4HA1) is the core active catalytic portion of prolyl 4-hydroxylase, and has contributed to tumorigenesis in several cancers. In this study, we identified that P4HA1 mRNA and protein are both up-regulated in non-small cell lung cancer (NSCLC). Besides, overexpressed P4HA1 is correlated with poor clinical outcomes and serve as an independent prognosis biomarker in lung adenocarcinoma (LUAD), but not lung squamous cell carcinoma (LUSC). In vitro studies, decreased P4HA1 significantly inhibits proliferation and cell cycle, by regulating cyclin-dependent kinases (CDKs), cyclins and CDK inhibitor (CKI). Moreover, via inhibiting epithelial-mesenchymal transition (EMT) and matrix metalloprotease (MMPs), dysregulation of P4HA1 could restrain the tumor cell invasion and metastasis of lung adenocarcinoma. In addition, we found that P4HA1 could enhance cell stemness and cisplatin-resistance in lung adenocarcinoma. In summary, P4HA1 plays a crucial role in the development of NSCLC and may provide a brand-new target for lung cancer treatment.

New insights into the important roles of tumor cell-intrinsic PD-1.

PD-1 (Programmed cell death protein-1) is mainly expressed in various immune cells, while its ligands PD-L1/PD-L2 (Programmed death ligand-1/Programmed death ligand-2) are mostly expressed in tumor cells. Generally, the binding of PD-L1/PD-L2 and PD-1 could lead to the tumor immune evasion. However, some recent studies showed that PD-1 could also be expressed in tumor cells and could activate mTOR (Mammalian Target of Rapamycin) or Hippo signaling pathway, therefore facilitating tumor proliferation independent of the immune system. While there was evidence that tumor cell-intrinsic PD-1 inhibited the activation of AKT and ERK1/2 pathways, thereby inhibiting tumor cell growth. Based on TCGA and CCLE database, we found that PD-1 was expressed in a variety of tumors and was associated with patient's prognosis. Besides, we found that PD-1 may be involved in many carcinogenic signaling pathway on the basis of PD-1 gene enrichment analysis of cancer tissues and cancer cells. Our understanding of the tumor cell-intrinsic PD-1 function is still limited. This review is aimed at elaborating the potential effects of tumor cell-intrinsic PD-1 on carcinogenesis, providing a novel insight into the effects of anti-PD-1/PD-L1 immunotherapy, and helping to open a major epoch of combination therapy.

Co-expression of PD-L1 and HIF-1α predicts poor prognosis in Patients with Non-small Cell Lung Cancer after surgery.

Purpose: PD-L1 is highly expressed in multiple cancers and suppresses anticancer immunity. HIF-1α, as a vital transcription factor, could regulate the proliferation, metastasis, and apoptosis of cancer cells. The aim of this study was to explore the correlation between PD-L1 and HIF-1α protein and further estimate its clinicopathological/prognostic impact on NSCLC patients. Methods: In this study, expression of PD-L1 and HIF-1α protein was detected by immunohistochemistry in tissue microarrays of NSCLC and non-cancerous tissues. Results: Expression of PD-L1 and HIF-1α protein was evidently elevated in NSCLC tissues compared with non-cancerous control lung tissues (both P<0.05). Also, PD-L1 was higher in male, lung SCC patients with lymph node metastasis (all P<0.05). There was a positive link between PD-L1 and HIF-1α in NSCLC (r=0.177, P=0.005). What's more, overall survival of lung ADC patients had to do with PD-L1 and clinical stage, while that of SCC patients was related to HIF-1α, pathological grade and LNM status (all P<0.05). Furthermore, multivariate analysis confirmed that PD-L1 and HIF-1α were considered to be independent prognostic factors for NSCLC patients (both P<0.05). Conclusion: PD-L1 and HIF-1α may serve as attractive independent worse prognostic biomarkers for NSCLC patients and the combined evaluation of PD-L1 and HIF-1α may also be valuable for prognosis judgment. Additionally, expression of PD-L1 was positively correlated with HIF-1α, which may provide evidences for a novel combinational therapy targeting PD-L1 and HIF-1α in NSCLC patients.

Overexpression of HSP10 correlates with HSP60 and Mcl-1 levels and predicts poor prognosis in non-small cell lung cancer patients.

BACKGROUND: HSP60 and its partner HSP10 are members of heat shock proteins (HSPs) family, which help mitochondrial protein to fold correctly. Mcl-1, a member of the Bcl-2 family, plays a crucial role in regulation of cell apoptosis. Aberrant expression of HSP10, HSP60 and Mcl-1 is involved in the development of many tumors. OBJECTIVE: To examine the association between expression of HSP10, HSP60 and Mcl-1 and clinicopathological features of non-small cell lung cancer (NSCLC). METHODS: Tissue microarrays including 53 non-cancerous lung tissues (Non-CLT) and 354 surgically resected NSCLC were stained with anti-HSP10, anti-HSP60 and anti-Mcl-1 antibodies respectively by immunohistochemistry. RESULTS: Higher expression of HSP10, HSP60 and Mcl-1 was found in NSCLC compared with Non-CLT. Both individual and combined HSP10 and HSP60 expression in patients with clinical stage III was higher than that in stage I ∼ II. Expression of HSP10 showed a positive correlation with HSP60 and Mcl-1. Overall survival time of NSCLC patients was remarkably shorter with elevated expression of HSP10, HSP60 and Mcl-1 alone and in combination. Moreover overexpression of HSP10 and Mcl-1 was poor independent prognostic factor for lung adenocarcinoma patients. CONCLUSIONS: High expression of HSP10, HSP60 and Mcl-1 might act as novel biomarker of poor prognosis for NSCLC patients.

Understanding the roles of stress granule during chemotherapy for patients with malignant tumors.

The assembly of stress granules (SGs) is a conserved mechanism to regulate protein synthesis under cell stress, where the translation of global protein is silenced and selective protein synthesis for survival maintains. SG formation confers survival advantages and chemotherapeutic resistance to malignant cells. Targeting SG assembly may represent a potential treatment strategy to overcome the primary and acquired chemotherapeutic resistance and enhance curative effect. We conduct a comprehensive review of the published literatures focusing on the drugs that potentially induce SGs and the related mechanism, retrospect the relationship between SGs and drug resistance related proteins, illuminate the regulated pathways and potential targets for SG assembly, and discuss future directions of overcoming the resistance to chemotherapy.

Comprehensive analysis of the mechanism and treatment significance of Mucins in lung cancer.

Aberrant expression of mucin proteins has played a complex and essential role in cancer development and metastasis. Members of the mucin family have been intimately implicated in lung cancer progression, metastasis, survival and chemo-resistance. During the progression of lung cancer, mucin proteins have involved all of the procession of lung cancer, which is interacted with many receptor tyrosine kinases signal pathways and mediated cell signals for tumor cell growth and survival. Mucins thus have been considerable as the indicator of negative prognosis and desirable therapeutic targets of lung cancers. In this review, we comprehensively analyzed the role of each member of the mucin family in lung cancer by combining open-accessed database analysis and assembling cutting-edge information about these molecules.

miR-4634 augments the anti-tumor effects of RAD001 and associates well with clinical prognosis of non-small cell lung cancer.

MicroRNA (miRNA) is involved in the physiological and pathological processes of various malignancies. In this study, miRNA microarray analysis showed that miR-4634 levels in A549 cells increased significantly after everolimus (RAD001) treatment. Decreased expression of miR-4634 was also found in non-small-cell lung carcinoma (NSCLC) cell lines and patients' tumors by qPCR. Additionally, a combination of miR-4634 and RAD001 exerted synergistic antitumor efficacy by inhibiting cell proliferation, migration, and colony formation. High expression of miR-4634 was significantly more common in non-cancerous lung tissue than adenocarcinoma or squamous cell carcinoma tissue (72.8%, 45.7%, and 50.9%, respectively; P < 0.001). Furthermore, high expression of miR-4634 was found to be more frequent in patients without lymph node metastasis (P = 0.037) by in-situ hybridization. Importantly, through univariate and multivariate analysis, high miR-4634 expression was associated with better prognosis of NSCLC patients. In conclusion, miR-4634 may act as a tumor suppressor in NSCLC, and to augment the efficacy of RAD001, co-treatment of miR-4634 and RAD001 might be a potential mTOR-targeted cancer therapy strategy for NSCLC patients. High expression of miR-4634 could be an independent good prognostic biomarker for NSCLC.

Overexpression of p-Akt, p-mTOR and p-eIF4E proteins associates with metastasis and unfavorable prognosis in non-small cell lung cancer.

The Akt (protein kinase B)/mammalian target of rapamycin (mTOR) pathway, which is dysregulated in various cancers, controls the assembly of eukaryotic translation initiation factor 4F (eIF4E) complex. However, whether aberrant expression of phosphorylated Akt (p-Akt), phosphorylated mTOR (p-mTOR) and phosphorylated eIF4E (p-eIF4E) is associated with clinicopathological characteristics in surgically resected non-small cell lung cancer (NSCLC) has been rarely reported. Here, we investigated expression of p-Akt, p-mTOR and p-eIF4E proteins in NSCLC by immunohistochemistry and evaluated their correlation with clinicopathological characteristics and prognostic significance. The results showed that the positive percentage of p-Akt, p-mTOR and p-eIF4E was higher in NSCLC. Additionally, p-mTOR and p-eIF4E was dramatically higher in lung adenocarcinoma (both P<0.05). Most importantly, NSCLC patients with lymph node metastasis had significantly elevated expression of p-Akt, p-mTOR and p-eIF4E (all P<0.05). Positive expression of p-Akt, and any positive expression of p-Akt, p-mTOR and p-eIF4E proteins were positively correlated with clinical stages (both P<0.05). Spearman's rank correlation test revealed that expression of p-Akt was correlated with p-eIF4E and p-mTOR (r = 0.107, P = 0.047; r = 0.287, P<0.001, respectively). Also, p-eIF4E had positive correlation with p-mTOR (r = 0.265, P<0.001). Furthermore, NSCLC patients with increased expression of p-Akt, p-mTOR and p-eIF4E, and any positive expression of above three proteins had lower overall survival rates (all P<0.05). Multivariate Cox regression analysis further indicated thatp-eIF4E was an independent prognostic factor for NSCLC patients (P = 0.046). Taken together, overexpression of p-Akt, p-mTOR and p-eIF4E proteins is associated with metastasis and poor prognosis of NSCLC patients after surgical resection, and positive expression of p-eIF4E protein may act as an independent unfavorable prognostic biomarker for overall survival of NSCLC patients.

Expression of DR5 and c­FLIP proteins as novel prognostic biomarkers for non­small cell lung cancer patients treated with surgical resection and chemotherapy.

TRAIL­R2 (DR5), one of the death receptors, can activate the extrinsic apoptosis pathway, while cellular FLICE­inhibitory protein (c­FLIP) can inhibit this pathway. Both of them play important roles in the occurrence and development of most tumors. To date, there is no relevant report concerning the relationship between expression of DR5 and c­FLIP protein and clinicopathological/prognostic implications in patients with non­small cell lung cancer (NSCLC) treated with surgical resection and chemotherapy. Thus, the aim of the present study was to investigate the potential prognostic significance of DR5 and c­FLIP in NSCLC patients and their predictive roles in the chemotherapeutic response. In the present study, DR5 and c­FLIP were detected by immunohistochemistry (IHC) in tissue microarrays of NSCLC. The results showed that the expression levels of DR5 and c­FLIP were significantly higher in lung squamous cell carcinoma (SCC) and lung adenocarcinoma (ADC) tissues compared with levels noted in the non­cancerous control lung tissues (all P<0.05). In addition, DR5 expression was significantly increased in lung ADC (P<0.001), whereas, c­FLIP was higher in lung SCC (P<0.001) and smoker patients with clinical stage III (P=0.019, P=0.016, respectively). In addition, NSCLC patients with overexpression of DR5 and loss of c­FLIP expression exhibited a higher overall survival (OS) rate as determined by Kaplan­Meier analysis (P=0.029, P=0.038, respectively). Multivariate analysis confirmed that high expression of DR5 and loss of c­FLIP expression were independent favorable prognostic factors for NSCLC patients (P=0.016, P=0.035, respectively). In conclusion, overexpression of DR5 and loss of c­FLIP expression may serve as novel favorable prognostic biomarkers for NSCLC patients treated with chemotherapy after radical resection and used as predictors for tumor response to chemotherapy drugs.

Elevated expression of G3BP1 associates with YB1 and p-AKT and predicts poor prognosis in nonsmall cell lung cancer patients after surgical resection.

PURPOSE: G3BP1 is an RNA-binding protein and plays roles in regulating signaling pathway. YB-1 is a DNA/RNA binding protein encoded by YBX1 gene. Phosphorylated AKT (p-AKT) acts as a pivotal molecule in PI3K/AKT pathway. YB-1 drives stress granules (SGs) formation by activating G3BP1 translation under diverse conditions. SGs are involved in many different metabolic and signaling pathways which may include PI3K/AKT/mTOR. So far, there has been no report on the relationship between expression of G3BP1, p-AKT, and YB1 and clinicopathological features/prognosis in surgically resected nonsmall cell lung cancer (NSCLC) patients. METHODS: In this study, data from TCGA (The Cancer Genome Atlas) were downloaded to investigate the mRNA expression of G3BP1 and YB1 (YBX1) and their correlation in NSCLC. Also, expression of G3BP1, YB1, and p-AKT proteins was studied using immunohistochemistry in tissue microarrays of NSCLC and in noncancerous lung tissues. RESULTS: We found that the mRNA expression of G3BP1 and YB1 was higher in NSCLC tissues (both P < .05), and G3BP1 was positively correlated with YB1 in mRNA level (r = .399, P < .001). Also, expression of G3BP1, YB1, and p-AKT proteins was higher in NSCLC tissues (all P < .05). And higher expression of G3BP1 and YB1 proteins was seen in patients with clinical stage II and III compared with stage I (both P < .05). Besides, expression of G3BP1 protein had a positive correlation with YB1 and p-AKT (both P < .05). Moreover, overall survival was shorter in patients with overexpression of G3BP1, YB1, and p-AKT proteins (all P < .05). Multivariate analysis confirmed that overexpression of G3BP1 protein was an independent poorer prognostic factor for NSCLC patients (P = .039). CONCLUSION: G3BP1 may play a crucial role in activating PI3K/AKT/mTOR pathway. G3BP1 might be served as a novel prognostic biomarker for surgically resected NSCLC patients, which afforded new insights into the study on the mechanism and therapy of NSCLC.

Prognostic analysis of patients with mutant and wild-type EGFR gene lung adenocarcinoma.

PURPOSE: The purpose of this study was to investigate the relationship between epidermal growth factor receptor (EGFR) gene mutation and clinicopathological features of lung adenocarcinoma, and the prognostic and therapeutic value of EGFR. METHODS: EGFR gene mutations were detected in 424 patients with lung adenocarcinoma by amplification refractory mutation system (ARMS). RESULTS: The total EGFR gene mutation rate was 55.2% (234/424) and EGFR gene mutation rates were statistically different in gender, smoking status, and pathological degree (P<0.05). The overall survival (OS) time of lung adenocarcinoma patients with mutation of exon 18 was lower than those with mutation of exon 19 and exon 21 (both P<0.05), but no significant difference was seen between those with mutation of exon 19 and exon 21 (P>0.05). Among 424 cases of lung adenocarcinoma, multivariate analysis showed that EGFR gene mutation, age, gender, clinical stages, and pathological degree (P<0.05) were statistically significant prognostic factors. In multivariate analysis, prognostic factors of patients with EGFR gene mutation were associated with EGFR-TKI treatment, surgery treatment, pathological degree, clinical stages, and age (P<0.05), whereas in patients without EGFR gene mutation, prognostic factors were related to surgery treatment, pathological degree, clinical stages, gender, age, and smoking status (P<0.05). CONCLUSION: The OS time of patients with mutation of exon 18 was lower than those of exon 19 and exon 21. EGFR-TKI treatment was an independent positive predictor in patients with EGFR gene mutation. Surgery treatment, age, clinical stages, and pathological degree were independent prognostic factors in Chinese patients with lung adenocarcinoma no matter whether with EGFR gene mutation or not.

Roles of exosomes in the carcinogenesis and clinical therapy of non-small cell lung cancer.

Lung cancer, with about 85% being non-small cell lung cancer (NSCLC), is one of the most common malignant tumors and the leading cause of cancer-related death in both men and women. Exosomes are defined as extracellular vesicles with a diameter of 30-100 nm, containing proteins, nucleic acids, lipids, etc., which are secreted by various cells in the microenvironment. Increasing evidences implicate that exosomes act as important molecular vehicles participating in physiological and pathological processes, such as tumor initiation, progression, and response to therapy in a number of human cancers including NSCLC. The aim of this review is to disclose the function of exosomes in NSCLC carcinogenesis, and discuss the potential clinical significance in the diagnosis, prognosis and of treatment NSCLC.