A Histopathologic Correlation Study Evaluating Glymphatic Function in Brain Tumors by Multi-Parametric MRI.

PURPOSE: This study aimed to elucidate the impact of brain tumors on cerebral edema and glymphatic drainage, leveraging advanced imaging techniques to explore the relationship between tumor characteristics, glymphatic function, and aquaporin 4 (AQP4) expression. EXPERIMENTAL DESIGN: In a prospective cohort from March 2022 to April 2023, patients with glioblastoma, brain metastases, and aggressive meningiomas, alongside age- and sex-matched healthy controls, underwent 3.0T MRI, including Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) index and Multiparametric MRI (MTP) for quantitative brain mapping. Tumor and peri-tumor tissues were analyzed for AQP4 expression via immunofluorescence. Correlations between imaging parameters, glymphatic function (DTI-ALPS index), and AQP4 expression were statistically assessed. RESULTS: Among 84 patients (mean age: 55 ± 12 years; 38 males) and 59 controls (mean age: 54 ± 8 years; 23 males), brain tumor patients exhibited significantly reduced glymphatic function (DTI-ALPS index: 2.315 vs. 2.879; p = 0.001) and increased cerebrospinal fluid (CSF) volume (201.376 cm³ vs. 115.957 cm³; p = 0.001). A negative correlation was observed between tumor volume and the DTI-ALPS index (r: -0.715, p < 0.001), while AQP4 expression correlated positively with peritumoral brain edema (PTBE) volume (r: 0.989; p < 0.001) and negatively with PD in PTBE areas (ρ: -0.506; p < 0.001). CONCLUSIONS: Our findings highlight the interplay between tumor-induced compression, glymphatic dysfunction, and altered fluid dynamics, showing the utility of DTI-ALPS and MTP in understanding the pathophysiology of tumor-related cerebral edema. These insights provide a radiological foundation for further neuro-oncological investigations into the glymphatic system.

G3BP1 Interact with JAK2 mRNA to Promote the Malignant Progression of Nasopharyngeal Carcinoma via Activating JAK2/STAT3 Signaling Pathway.

Ras-GTPase-activating protein (GAP)-binding protein 1 (G3BP1) is an RNA-binding protein implicated in various malignancies. However, its role in nasopharyngeal carcinoma (NPC) remains elusive. This study elucidates the potential regulation mechanisms of G3BP1 and its significance in NPC advancement. Through knockdown and overexpression approaches, we validate G3BP1's oncogenic role by promoting proliferation, migration, and invasion in vitro and in vivo. Moreover, G3BP1 emerges as a key regulator of the JAK2/STAT3 signaling pathway, augmenting JAK2 expression via mRNA binding. Notably, epigallocatechin gallate (EGCG), a green tea-derived antioxidant, counteracts G3BP1-mediated pathway activation. Clinical analysis reveals heightened G3BP1, JAK2, and p-STAT3 as powerful prognostic markers, with G3BP1's expression standing as an independent indicator of poorer outcomes for NPC patients. In conclusion, the study unveils the oncogenic prowess of G3BP1, its orchestration of the JAK2/STAT3 signaling pathway, and its pivotal role in NPC progression.

Efficacy of indocyanine green fluorescence-guided inguinal lymph node dissection for penile cancer: a randomised trial.

OBJECTIVES: To investigate the safety and efficacy of indocyanine green (ICG) fluorescence-guided inguinal lymph node dissection (ILND) in patients with penile cancer. PATIENTS AND METHODS: A prospective, single-blind, randomised controlled clinical trial (ChiCTR2100044584) was performed among patients with penile caner who underwent bilateral modified ILND at four centres in China between 1 April 2021 and 30 June 2022. Patients aged 18-80 years and diagnosed with squamous cell carcinomas were included. Each enrolled patient was randomly assigned to either ICG fluorescence-guided ILND by a laparoscopic or robot-assisted approach in one groin, with non-ICG fluorescence-guided ILND in the other groin acting as a control. The primary outcome was the number of retrieved ILNs. Secondary outcomes included complications according to the Clavien-Dindo classification and the ILN non-compliance (inadequate removal of ILNs) rate. RESULTS: A total of 45 patients were included in the intention-to-treat (ITT) analysis, and the 42 who completed the entire study were included in the per protocol (PP) analysis. There were no ICG-related complications in any of the patients. The results of the ITT and PP analyses indicated that the total number of unilateral ILNs retrieved was higher on the ICG side than on the non-ICG side (mean 13 vs 9 ILNs, difference 4 ILNs [95% CI 2.7-4.4], P = 0.007), and the number of unilateral deep and superficial ILNs was higher on the ICG side. Furthermore, the LN non-compliance rate was lower on the ICG side than on the non-ICG side. Additionally, there was no significant difference in local complications in the groins between the two sides (P > 0.05). CONCLUSION: An ICG fluorescence-guided ILND was safe for patients with penile cancer. This procedure can improve the number of ILNs retrieved and reduce the LN non-compliance rate without increased complications. ICG fluorescence-guided ILND is beneficial and recommended for selected patients with penile cancer.

Somatostatin receptor2 (SSTR2) expression, prognostic implications, modifications and potential therapeutic strategies associates with head and neck squamous cell carcinomas.

Head and neck squamous cell carcinomas (HNSCC) constitute a heterogeneous cluster of tumors celebrated for their predisposition to metastasize and exhibit local recurrence. Recent explorations have illuminated the intricate involvement of Somatostatin Receptor 2 (SSTR2), a growth-regulatory receptor traditionally classified as a tumor suppressor, yet concurrently implicated in bolstering specific tumor phenotypes. Advances in the realm of SSTR2 investigation within HNSCC, with a specific spotlight on laryngeal squamous cell carcinomas (LSCC), tongue squamous cell carcinomas (TSCC), and nasopharyngeal carcinomas (NPC), have been established. This study aims to provide a comprehensive overview of SSTR2 expression patterns, prognostic implications, distinctive signaling pathways, epigenetic modifications, and potential therapeutic strategies associated with SSTR2 in HNSCC.

High expression of HSP60 and survivin predicts poor prognosis for oral squamous cell carcinoma patients.

BACKGROUND: HSP60 is a heat shock proteins (HSPs) family member and help mitochondrial protein to fold correctly. Survivin is one of the inhibitors of apoptosis protein family member, which plays a significant part in cancer progression. They were capable of forming HSP60-survivin complexes and involved in the development of various tumors. METHODS: The Cancer Genome Atlas (TCGA) database demonstrated that HSP60 and survivin and their correlation on mRNA expression level with OSCC patients. Besides, expression of HSP60 and survivin proteins was studied utilizing immunohistochemistry in tissue microarrays (TMA) in OSCC and in adjacent non-cancerous squamous epithelium (Non-CCSE) tissues. RESULTS: Significantly increased levels of HSP60 and survivin in most cancers compared to normal tissue by pan-cancer analysis. HSP60 and survivin proved a significantly increased expression in OSCC samples compared to Non-CCSE both on mRNA and protein (both P < 0.05). Additionally, elevated HSP60 displayed a positive correlation with survivin in terms of mRNA and protein expression levels (all P < 0.001). Patients with OSCC who had advanced clinical stage or lymph node metastasis (LNM) showed higher HSP60 expression (P = 0.004, P = 0.006, respectively). Higher levels of the proteins HSP60 and survivin were significantly inversely correlated relationship with OSCC patients' overall survival rates in multivariate survival analysis (P = 0.018, P = 0.040). From the above results, overexpression of HSP60 and survivin protein may serve as independent biomarkers predicting poor prognosis in OSCC. CONCLUSIONS: Elevated HSP60 and survivin might be served as novel poor prognosis biomarkers for surgically resected OSCC patients.

AXL in cancer: a modulator of drug resistance and therapeutic target.

AXL is a member of the TAM (TYRO3, AXL, and MERTK) receptor tyrosine kinases family (RTKs), and its abnormal expression has been linked to clinicopathological features and poor prognosis of cancer patients. There is mounting evidence supporting AXL's role in the occurrence and progression of cancer, as well as drug resistance and treatment tolerance. Recent studies revealed that reducing AXL expression can weaken cancer cells' drug resistance, indicating that AXL may be a promising target for anti-cancer drug treatment. This review aims to summarize the AXL's structure, the mechanisms regulating and activating it, and its expression pattern, especially in drug-resistant cancers. Additionally, we will discuss the diverse functions of AXL in mediating cancer drug resistance and the potential of AXL inhibitors in cancer treatment.

YAP1 synergize with YY1 transcriptional co-repress DUSP1 to induce osimertinib resistant by activating the EGFR/MAPK pathway and abrogating autophagy in non-small cell lung cancer.

YAP1 is a well-known core effector of the Hippo pathway in tumors, but its potential role in osimertinib resistance remained unexplored. Our study provides evidence that YAP1 acts as a potent promoter of osimertinib resistance. By inhibiting YAP1 with a novel inhibitor, CA3, and combining it with osimertinib, we observed a significant suppression of cell proliferation and metastasis, induction of apoptosis and autophagy, and a delay in the emergence of osimertinib resistance. Interestingly, CA3 combined with osimertinib executed its anti-metastasis and pro-tumor apoptosis in part through autophagy. Mechanistically, we found that YAP1, in collaboration with YY1, transcriptionally represses DUSP1, leading to the dephosphorylation of the EGFR/MEK/ERK pathway and YAP1 phosphorylation in osimertinib-resistant cells. Our results also validate that CA3, in combination with osimertinib, executes its anti-metastasis and pro-tumor apoptosis partly through autophagy and the YAP1/DUSP1/EGFR/MEK/ERK regulatory feedback loop in osimertinib-resistant cells. Remarkably, our findings illustrate that YAP1 protein is upregulated in patients after osimertinib treatment and osimertinib resistance. Overall, our study confirms that the YAP1 inhibitor CA3 increases DUSP1 with concomitant activation of the EGFR/MAPK pathway and induces autophagy to enhance the efficacy of third-generation EGFR-TKI treatments for NSCLC patients.

Increased expression of FAT4 suppress metastasis of lung adenocarcinoma through regulating MAPK pathway and associated with immune cells infiltration.

FAT4 is an extremely large atypical cadherin with crucial roles in the control of planar cell polarity (PCP) and regulation of the Hippo signaling pathway. Our study aims to clarify the FAT4 expression patterns, as well as the significance of FAT4 in predicting the prognosis and cancer immunity to non-small cell lung cancer (NSCLC). FAT4 mRNA and protein expressions were both underregulated in NSCLC and associated with poor prognosis in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). In addition, overexpress FAT4 with jujuboside A (JUA) or knockdown FAT4 with siRNA regulated the metastasis of LUAD through MAPK pathways. Moreover, the FAT4 expression included multiple immunological components to promote an immunosuppressive tumor microenvironment (TME). Furthermore, a study of the TCGA-LUAD cohort's DNA methylation results showed that most FAT4 DNA CpG sites were typically hypermethylated in NSCLC relative to the normal lung tissue. The DNA CpG sites cg25879360 and cg26389756 of FAT4 were found to be strongly associated with FAT4 expression in LUAD through the correlation study. In conclusion, this is the first to report the potential function of FAT4 in NSCLC. Hence, FAT4 could be used as a promising prognostic and immunological biomarker for NSCLC.

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.

Inflammatory Myofibroblastic Tumor of the Urinary Bladder: An 11-Year Retrospective Study From a Single Center.

Purpose: To share our experience in the diagnosis and treatment of an inflammatory myofibroblastic tumor of the urinary bladder (IMTUB). Materials and Methods: A database searches in the pathology archives by using the term "inflammatory myofibroblastic tumor" and" bladder" in our hospital department of pathology from 2010 to 2021. Patient characteristics, clinical features, histopathological results, immunohistochemical staining results, and treatment outcomes were reviewed. Results: Fourteen cases of IMTUB were retrieved. The mean age was 44.7 ± 18.9 years (range 12-74). Nine (64.3%) of the patients presented with hematuria, followed by seven (50%) with odynuria, five (35.7%) with urgent urination, and one (7.1%) with dysuria. Ten (71.4%) of the patients were treated with partial cystectomy (PC), three (21.4%) with transurethral resection of bladder tumor (TURBT), and one (7.1%) with radical cystectomy (RC). Histopathologically, eight (57.1%) had a compact spindle cell pattern. Anaplastic lymphoma kinase (ALK) staining was positive in six (75%) of 8 cases. During a mean follow-up period of 43.9 ± 38 months (range 3-117), a patient had recurrence within half a month. Then, the patient was treated with further TURBT surgery and had no recurrence within 6 months. Thirteen of the patients had no local recurrence or distant metastasis. Conclusion: Inflammatory myofibroblastic tumor of the urinary bladder (IMTUB) is clinically rare and has a good prognosis. The disease is mainly treated with surgery to remove the tumor completely. It can easily be misdiagnosed as bladder urothelial carcinoma, leiomyosarcoma, or rhabdomyosarcoma, which may result in overtreatment and poor quality of life of patients.

Hyperprogressive Disease After Immunotherapy: A Case Report of Pulmonary Enteric Adenocarcinoma.

Primary pulmonary enteric adenocarcinoma (PEAC) is a rare invasive adenocarcinoma clinically similar to metastatic colorectal adenocarcinoma (MCRC). Although many studies have addressed the differential diagnosis of PEAC, few have described the treatment of PEAC, especially using immunotherapy. This report describes a 61-year-old man who presented initially with pain in the ribs. Pathological analysis of biopsy samples shows malignant tumors of the right pleura, and next-generation sequencing of 26 genes showed a KRAS gene mutation. Positron emission tomography-computed tomography (PET-CT) found no evidence of gastrointestinal malignancy. Due to multiple metastases, the patient could not undergo radical surgery. The patient was treated with a combination chemotherapy regimen of paclitaxel plus carboplatin, along with sindilizumab immunotherapy, but, after one cycle of treatment, the tumor showed a hyperprogressive state. The patient is still being monitored regularly. These findings indicate that chemotherapy combined with immunotherapy may be ineffective in the treatment of primary PEAC with positive driver genes.

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.

USP5 facilitates non-small cell lung cancer progression through stabilization of PD-L1.

PD-L1(CD274) is a well-known immunosuppressive molecule, which confers immunoescape features to cancer cells and has become one of the major targets in cancer immunotherapies. Understanding the regulatory mechanisms that control PD-L1 protein expression is important for guiding immune checkpoint blockade therapy. Here, we showed that ubiquitin specific peptidase 5 (USP5) was a novel PD-L1 deubiquitinase in non-small cell lung cancer (NSCLC) cells. USP5 directly interacted with PD-L1 and deubiquitinated PD-L1, therefore enhances PD-L1 protein stability. Meanwhile, USP5 protein levels were highly elevated and positively correlated to PD-L1 levels in NSCLC tissues, and were closely correlated with poor prognosis of these patients. In addition, knockdown of USP5 retarded tumor growth in the Lewis lung carcinoma mouse model. Thus, we identified that USP5 was a new regulator of PD-L1 and targeting USP5 is a promising strategy for cancer therapy.

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.

Targeting c-Myc to Overcome Acquired Resistance of EGFR Mutant NSCLC Cells to the Third-Generation EGFR Tyrosine Kinase Inhibitor, Osimertinib.

Osimertinib (AZD9291 or TAGRISSO) is a promising and approved third-generation EGFR tyrosine kinase inhibitor (TKI) for treating patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR-activating mutations or the resistant T790M mutation. However, the inevitable emergence of acquired resistance limits its long-term efficacy. A fuller understanding of the mechanism of action of osimertinib and its linkage to acquired resistance will enable the development of more efficacious therapeutic strategies. Consequently, we have identified a novel connection between osimertinib or other EGFR-TKIs and c-Myc. Osimertinib rapidly and sustainably decreased c-Myc levels primarily via enhancing protein degradation in EGFR-mutant (EGFRm) NSCLC cell lines and xenograft tumors. c-Myc levels were substantially elevated in different EGFRm NSCLC cell lines with acquired resistance to osimertinib in comparison with their corresponding parental cell lines and could not be reduced any further by osimertinib. Consistently, c-Myc levels were elevated in the majority of EGFRm NSCLC tissues relapsed from EGFR-TKI treatment compared with their corresponding untreated baseline c-Myc levels. Suppression of c-Myc through knockdown or pharmacologic targeting with BET inhibitors restored the response of resistant cell lines to osimertinib. These findings indicate that c-Myc modulation mediates the therapeutic efficacy of osimertinib and the development of osimertinib acquired resistance. Furthermore, they establish c-Myc as a potential therapeutic target and warrant clinical testing of BET inhibition as a potential strategy to overcome acquired resistance to osimertinib or other EGFR inhibitors. SIGNIFICANCE: This study demonstrates a critical role of c-Myc modulation in mediating therapeutic efficacy of osimertinib including osimertinib acquired resistance and suggests targeting c-Myc as a potential strategy to overcome osimertinib acquired resistance.

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.

Overexpression of FADD and Bcl-XS proteins as novel prognostic biomarkers for surgically resected non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most widespread cancer with increasing morbidity and mortality. FAS-associated protein with death domain (FADD) is considered as an essential instrument in cell death, whereas Bcl-XS promotes apoptosis through inhibiting the activity of Bcl-2 and Bcl-XL. OBJECTIVE AND METHODS: We detected the expression of FADD and Bcl-XS in resected NSCLC tissues by immunohistochemistry, and investigated their association with clinicopathological characteristics and prognostic significance of NSCLC patients. RESULTS: Bcl-XS expression was significantly increased in well and moderate differentiated lung SCC (P= 0.004). Lung ADC patients with overexpression of FADD and lung SCC patients with low expression of Bcl-XS had importantly lower overall survival rates by Kaplan-Meier analysis (P= 0.033, P= 0.02, respectively). Multivariate analysis confirmed that elevated expression of FADD was an independent poor prognostic factor for patients with surgically resected lung ADC (P= 0.027) and increased expression of Bcl-XS was an independent good prognostic factor for patients with surgically resected lung SCC (P= 0.016)CONCLUSION: Elevated expression of FADD was identified as independent poor prognostic factor for patients with surgically resected lung ADC, however, increased expression of Bcl-XS was an independent good prognostic biomarker for patients with surgically resected lung SCC.

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.

Hyperprogression After Immune-Checkpoint Inhibitor Treatment: Characteristics and Hypotheses.

Immunotherapies in tumors have attracted increasing attention. They play an important role in precision medicine. Many immune-checkpoint inhibitors (ICIs) have obtained FDA approval and show good performance in the clinic. Hyperprogressive disease (HPD) after ICIs was first described in November 2016. Since then, a series of cases of HPD after ICIs have been reported. Notwithstanding that only a small subset of patients may experience this atypical response, HPD in affected patients means shorter survival times and worse prognoses. We summarized common standards for HPD diagnosis and profiled advantages and disadvantages. Elderly age, MDM2 family amplification, infiltration of PD-1-positive regulatory effector T cells and M2-like macrophages, and cancer stem cells may take part in HPD occurrence. Overall, we should focus on investigating the early markers and pathogenic mechanisms of HPD to solve this issue in ICIs.