Mitochondria-associated endoplasmic reticulum membranes (MAMs) are dynamic contact sites between the endoplasmic reticulum (ER) and mitochondria that coordinate multiple cellular processes such as calcium signaling, lipid trafficking, and redox homeostasis. Increasing evidence shows that cancer cells remodel MAMs to support metabolic adaptation, stress tolerance, tumor progression, and therapeutic resistance. In this review, we summarize the structural organization of MAMs, the core tethering and regulatory mechanisms governing their plasticity, and emerging evidence linking MAM dysfunction to malignant phenotypes and therapeutic resistance. We highlight that the roles of MAM-associated proteins in cancer are highly context-dependent, varying with tumor type, metabolic state, and therapeutic pressure. We further discuss emerging therapeutic strategies targeting MAM-associated pathways, as well as combination approaches to overcome resistance. A better mechanistic understanding of MAM remodeling may reveal actionable vulnerabilities and support biomarker-guided precision therapy across cancer types.

Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality. N4-acetylcytidine (ac4C) modification regulates mRNA stability and translation, but the role of its associated co-factor, THUMP domain-containing protein 1 (THUMPD1), in cancer is unknown. Clinical LUAD samples and Gene Expression Omnibus (GEO) datasets were analyzed for THUMPD1 expression and prognosis. In vitro and in vivo functional assays were performed to assess the impact of THUMPD1 on LUAD. Multi-omics approaches and mechanistic studies were employed to identify downstream targets and signaling pathways. THUMPD1 was significantly downregulated in advanced-stage LUAD. THUMPD1 acted as a tumor suppressor, inhibiting LUAD cell proliferation, metastasis, and tumor growth in mouse models. Mechanistically, THUMPD1 directly bound to and upregulated the translation of insulin-like growth factor 2 receptor (IGF2R) mRNA in an ac4C-independent manner by facilitating its cytoplasmic localization. The THUMPD1-IGF2R axis inhibited AKT signaling, which in turn led to the activation of AMPK. This resulted in intracellular Cu+ accumulation, triggering cuproptosis and excessive mitophagy, ultimately suppressing tumor growth. Therapeutically, the copper ionophore elesclomol potently inhibited tumor growth in a Thumpd1-knockout mouse model of LUAD.

The role and underlying mechanisms of G protein-coupled receptor 87 (GPR87) in esophageal squamous cell carcinoma (ESCC) remain unclear, despite its established oncogenic functions in other malignancies. This study examined the expression of GPR87 and its association with survival rate in ESCC using online databases. The expression of GPR87 in ESCC tissues was identified using immunohistochemistry, and a correlation analysis was carried out using ki-67 data. ESCC cells were transfected with GPR87 knockdown or overexpression plasmids, followed by functional assays such as, CCK-8 for cell viability, colony formation for proliferation, wound healing for migration, Transwell for invasion, and tube formation for angiogenesis. Western blot analysis was used to assess STAT3 phosphorylation and VEGFA expression. Additionally, a xenograft tumor model was established to investigate the effect of GPR87 on tumor growth in vivo. The findings demonstrated that GPR87 was highly expressed in ESCC tissues and its overexpression was associated with a poor patient survival. Transfection with a GPR87 overexpression plasmid increases the cell viability, invasion, proliferation, and angiogenesis of ESCC cells, while transfection with sh-GPR87 reversed these effects. Additionally, GPR87 controlled VEGFA expression levels by promoting STAT3 phosphorylation. Rescue trials further verified that GPR87 promotes the growth of ESCC by modulating STAT3. Moreover, in vivo studies validated that GPR87 knockdown suppressed tumor growth. In conclusion, the findings highlight GPR87 as a key regulator of VEGFA expression via STAT3 activation, contributing to ESCC malignancy. Targeting GPR87 may provide a potential therapeutic strategy for ESCC.

Neoadjuvant chemotherapy (NACT) represents a non-invasive treatment paradigm for both locally advanced and early-stage breast cancer patients. Precise prediction of NACT treatment response is pivotal in postoperative treatment planning and prognostic enhancement. While pathologic puncture remains a central method for evaluating NACT response, its invasive nature not only induces adverse effects but also elevates the risk of delayed surgery. To this end, this paper proposes CITR-Net, an innovative multi-modality fusion framework which ingeniously combines Clinicopathologic Information with Tumor Region characteristics to achieve precise prediction of NACT treatment response. Leveraging a dual-stream encoder with paralleled parameter-shared attention (P2SA) gates, CITR-Net adeptly captures both texture and intensity features from tumor regions before and after contrast agent injection. Simultaneously, clinicopathologic information extracted from clinical and pathology tabular data is tokenized to facilitate feature representation. A novel clinicopathologic information-enhanced feature fusion (CIF-Fusion) strategy seamlessly merges these feature representations, enabling a comprehensive exploration of tumor-related features across image and tabular data domains. Furthermore, CITR-Net employs a tumor region-based decoder, guided by a tumor region-supervised loss, to ensure intricate details of tumor areas are preserved during the encoding phase. Experimental evaluations conducted on two publicly available datasets demonstrate CITR-Net’s superior performance compared to existing state-of-the-art methods. In summary, CITR-Net emerges as a efficient and effective tool for accurately predicting NACT treatment response, paving the way for improved patient care and prognostic outcomes in breast cancer treatment. The code will be released on GitHub (https://github.com/LTYUnique/CITR-Net).

BACKGROUND:Lung transplantation offers a life-saving procedure to patients with end-stage lung diseases with 85-89 % one year and 60 % five-year survival rates. Lung transplants are complicated by early ischemia/reperfusion injury (IRI) and late chronic lung allograft dysfunction (CLAD). However, the cellular and molecular links between IRI and CLAD remain unclear. MATERIALS AND METHODS:We integrated single-cell RNA-seq results from GSE220797 and GSE224210 data sets. After quality filtering, we performed Louvain clustering and UMAP visualization. We applied Augur method to prioritize cell populations by transcriptional responsiveness to IRI and CLAD. We also performed dynamic trajectory analyses to map pseudotemporal transitions. Pathway activity was characterized by differential expression analysis and module scoring. Intercellular communication was assessed using CellChat and MEBOCOST analyses. Regulon inference was performed with pySCENIC analysis. RESULTS:Overall, epithelial cells showed progressive metabolic suppression and activation of cuproptosis, a programmed cell death (PCD) triggered by excessive copper accumulation within cells. Club cells, found in the small airways of the lungs, exhibited developmental plasticity and predictive potential across IRI and CLAD conditions. Among myeloid populations, M1 proinflammatory (AM_M1TM) macrophages underwent macrophage-to-myofibroblast transition (MMT) and produced excessive extracellular matrix (ECM) supporting a network of proteins surrounding cells. Metabolite and cell-cell communication analyses revealed declining macrophage/epithelial metabolic crosstalk and differential signaling flux from normal through IRI to CLAD transition. CONCLUSIONS:The integrated single-cell atlas delineates interaction of multiple cells and their signaling pathways linking IRI to CLAD processes. These findings require further verification through studies in animal models and clinical samples.

Glutamine metabolism is a hallmark of cancer metabolism, which matters in the progression of the tumor. This synthetic study conducted a large-scale systematic analysis at the pan-cancer level on the glutamate and glutamine metabolism (GGM) across 32 solid tumors from the TCGA database. The glutamine metabolism activity was quantified through a scoring system. This study revealed that the GGM score in tumor tissues was up-regulated in 13 cancer types (BCLA, BRCA, COAD, KICH, KIRP, LUAD, LUSC, PAAD, PRAD, READ, STAD, THYM, UCEC) and down-regulated in 4 cancer types (CHOL, GBM, LIHC, THCA), exhibiting tissue specificity. The mRNA expression levels of glutamine metabolism-related genes were relatively high, and GLUL exhibited the highest expression level. The expression levels were up-regulated with copy number amplification. ALDH18A1, PYCR1, and PYCR2 show a significant upregulation in protein levels in cancer tissues compared to normal tissues, making them potential pan-cancer therapeutic targets. For the TME related to glutamine metabolism, the GGM score exhibited significant immune and stromal environment inhibitory effects in all involved tumors. Up-regulated GGM score indicated the widespread promotion of drug resistance at the pan-cancer level. GGM score and glutamine metabolism-related genes signature tended to be risk factors for the overall survival of cancer patients.

Background To observe the occurrence of related complications after self-expandable metallic (SEM) airway stents implantation with different diameters at different time points, and to provide theoretical basis for the optimal chioce of existing airway stents in clinical practice. Methods Healthy New Zealand white rabbits were used to establish benign tracheal stenosis models after chest CT examination. Forty-fivemodel rabbits with more than 50% of airway stenosis were divided into two groups. Small-diameter SEM stents (The ratio of stent diameter to airway diameter is nearly 1.0) were implanted in Group A in 21 rabbits, and large-diameter tracheal stents (The ratio of stent diameter to airway diameter is more than 1.2) were implanted in Group B in 24 rabbits. Stent-related complications were observed after stent implantation in 2nd,4th,8th, and 12th week by bronchoscopygross anatomy, pathological and the expressions of IL-1RA, IL-8 and MMP9 in involved tracheal. Results The incidence rate of tracheomalacia of stent was significantly higher in group B (24/24 100%) than that in group A (1 /21,4.8%) ( P < 0.05). The incidence rate of scar contracture at both ends of stent was significantly higher than in group B (11 / 24,45.8%) that in group A (2 /21, 9.5%) ( P < 0.05). The pathological results of both A and B showed that the columnar epithelium of bronchial mucosa began to damage and detach, inflammatory cells infiltrated after 2nd and 4th week of stenting, The epithelium was repaired, the lamina propria glands almost disappeared, collagen fiber proliferation was obvious, and scars were formed after 8th and 12th week of stenting. ELISA results revealed that the expressions of IL-1RA, IL-8, and MMP9 were increased in the stent group than in model rabbit with benign tracheal stenosis. IL-1RA and MMP9 increased at different periods in group B, but the expression of IL-1RA and MMP9 showed a tread of increasing in the early stage and then decreasing in group A. Conclusion Metal stents can cause different degrees of stent-related complications in rabbits with benign tracheal stenosis. The incidence of stent-induced tracheomalacia and scar contracture were higher in Group B than that in Group A. IL-1RA, IL-8 and MMP9 may be involved in the development of complications after stentimplantation and peak value of group B movered backward. ing.

Esophageal cancer is a major malignancy with a high incidence and poor prognosis. To elucidate the mechanisms underlying its progression, particularly with respect to cell division and spindle orientation, we investigated the role of m6A modifications and the centrosomal protein CEP170. Using m6A-seq and RNA-seq of esophageal cancer tissues and adjacent normal tissues, we identified significant alterations in m6A modifications and gene expression, highlighting the upregulation and m6A enrichment of CEP170 in tumor tissues. Functional assays, including cell cycle synchronization, qPCR, immunoblotting, immunofluorescence, coimmunoprecipitation, methylated RNA immunoprecipitation, and cell proliferation assays, demonstrated that CEP170 plays a critical role in mitotic progression and spindle orientation. m6A-seq and RNA-seq revealed significant alterations in m6A modifications and gene expression in esophageal cancer. CEP170 was upregulated and highly enriched in m6A modifications in tumor tissues. Functional assays revealed that CEP170 plays a critical role in proper mitotic progression and spindle orientation. Knockdown of CEP170 led to spindle misorientation and impaired the stability of astral microtubules. Additionally, CEP170 affected the localization of the dynein/dynactin motor complex in the cell cortex. METTL3 was upregulated in tumor tissues and regulated CEP170 expression. RNA-seq upon CEP170 depletion revealed that ASPM was significantly downregulated, indicating its involvement as a downstream target of CEP170 in regulating cell proliferation and mitosis. Our findings provide novel insights into the molecular mechanisms by which CEP170 and m6A modifications regulate esophageal cancer progression, revealing that CEP170 is a potential therapeutic target.

Epigenetic modifications play critical roles in gene regulation and disease pathobiology. Highly sensitive enabling technologies, including microarray- and sequencing-based approaches have allowed genome-wide profiling of cytosine modifications in DNAs in clinical samples to facilitate discovery of epigenetic biomarkers for disease diagnosis and prognosis. Historically, many previous studies, however, did not distinguish the most investigated 5-methylcytosines (5mC) from other modified cytosines, especially the biochemically stable 5-hydroxymethylcytosines (5hmC), which have been shown to have a distinct genomic distribution and regulatory role from 5mC. Notably, during the past several years, the 5hmC-Seal, a highly sensitive chemical labeling technique, has been demonstrated to be a powerful tool for genome-wide profiling of 5hmC in clinically feasible biospecimens (e.g. a few milliliter of plasma or serum). The 5hmC-Seal technique has been utilized by our team in biomarker discovery for human cancers and other complex diseases using circulating cell-free DNA (cfDNA), as well as the characterization of the first 5hmC Human Tissue Map. Convenient access to the accumulating 5hmC-Seal data will allow the research community to validate and re-use these results, potentially providing novel insights into epigenetic contribution to a range of human diseases. Here we introduce the PETCH-DB, an integrated database that was implemented to provide 5hmC-related results generated using the 5hmC-Seal technique. We aim the PETCH-DB to be a central portal, which will be available to the scientific community with regularly updated 5hmC data in clinical samples to reflect current advances in this field. Database URL http://petch-db.org/.

Inflammation is an important risk factor in the development of inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC). Accumulating evidence indicates that some phytochemicals have anti-cancer properties. Polysaccharides extracted from Albuca bracteata (AB) have been reported to possess anti-neoplastic activities on colorectal cancer (CRC) models. However, it is still unclear whether they exert therapeutic effects on colorectal cancer. In this study, we investigate the properties of polysaccharides of A. bracteate, named ABP. The average molecular weight of ABP was 18.3 kDa and ABP consisted of glucose, mannose, galactose, xylose, galacturonic acid, glucuronic acid at a molar ratio of 37.8:8:2.5:1.7:1:1. An Azoxymethane/Dextran sodium sulfate (AOM/DSS) induced CAC mouse model was established. The CAC mice treated with ABP showed smaller tumor size and lower tumor incidence than untreated ones. ABP increased anti-inflammatory cytokine IL-10, inhibited secretion of pro-inflammatory cytokines (IL-6, IFN-γ, and TNF-α), mitigated oxidative stress by increasing GSH and decreasing MDA levels, suppressed the activation of STAT3 and expressions of its related genes c-Myc and cyclin D1. Moreover, ABP treatment increased the relative abundance of beneficial bacteria (f_Ruminococcaceae, g_Roseburia, g_Odoribacter, g_Oscillospira, and g_Akkermansia) and the levels of fecal short-chain fatty acid (SCFA) in CAC model mice. In summary, our data suggest that ABP could be a potential therapeutic agent for treating CAC.

Additional file 6: Table S2. Correlation analysis between HDAC3 expression and clinicopathological characteristics of patients with esophageal squamous cell carcinoma.

The incidence of cutaneous melanoma (CM) has been increasing annually worldwide. In this study, we identify that MrgprF, a MAS related GPR family member, is decreased in cutaneous melanoma tissues and cell lines due to hypermethylation of its promoter region, and show that patients with CM expressing high levels of MrgprF exhibit an improved clinical outcome. We demonstrate that MrgprF forced expression inhibits tumor cell proliferation, migration, xenograft tumor growth, and metastasis. On the contrary, MrgprF knockdown promotes tumor cell proliferation and transformation of immortalized human keratinocyte-HaCaT cells, supporting the inhibitory role of MrgprF during tumor progression. Mechanistic studies reveal that MrgprF reduces the phosphoinositol‑3‑kinase (PI3K) complex formation between p101 and p110γ subunits, the critical step for phosphatidylinositol-(3, 4)-P2 (PIP2) conversion to phosphatidylinositol-(3, 4, 5)-P3 (PIP3), and then reduces the activation of PI3K/Akt signaling. This effect can be reversed by Akt specific agonist SC79. In addition, AMG 706, a previously documented inhibitor for endothelial cell proliferation, is identified as a potential agonist for MrgprF, and can impede tumor growth both in vitro and in vivo. Taken together, our findings suggest that MrgprF, a novel tumor suppressor in cutaneous melanoma, may be useful as a therapeutic target in the future.

Background:Pembrolizumab and sintilimab have both been approved by the China National Medical Products Administration (NMPA) for the first-line treatment of advanced non-small cell lung cancer (NSCLC). These two drugs have several differences in biological characteristics and population in clinical trials. The current retrospective study was conducted to compare the efficacy and safety of sintilimab and pembrolizumab as first-line treatments in patients with advanced NSCLC.Methods:Consecutive patients with advanced NSCLC who received sintilimab or pembrolizumab as first-line therapy, with or without chemotherapy, from November 2018 to October 2021 in the First Affiliated Hospital of Soochow University and Dushu Lake Hospital Affiliated to Soochow University were retrospectively reviewed. Clinical data and treatment response were collected and survival was followed up. Kaplan-Meier method was used to estimate survival curves. The patients were divided into the sintilimab group and the pembrolizumab group according to the PD-1 inhibitors they received during treatment. The primary objective was to compare objective response rate (ORR) and progression-free survival (PFS) between the two groups. The secondary objectives were to compare disease control rate (DCR) and analyze adverse events (AEs) of the two groups.Results:A total of 124 patients were enrolled, including 68 patients (54.8%) in the sintilimab group and 56 patients (45.2%) in the pembrolizumab group. The baseline characteristics of the patients were comparable between the two groups. The ORR was 50% in the sintilimab group and 46.4% in the pembrolizumab group (P=0.69). The DCR was 89.7% and 89.3% in the sintilimab group and the pembrolizumab group, respectively (P=0.94). The median PFS time was 9.9 months in patients treated with sintilimab compared to 10.8 months in patients on pembrolizumab treatment [hazard ratio (HR) =0.960; 95% confidence interval (CI): 0.574-1.606; P=0.875]. The median OS time was not reached in either group of patients. The incidence of grade 3-4 treatment-related adverse events (TRAEs) was 25% (17/68) in the sintilimab group and 21.4% (12/56) in the pembrolizumab group.Conclusions:Sintilimab has similar efficacy to pembrolizumab as a first-line treatment option for patients with advanced NSCLC in clinical practice, with manageable AEs.

Background: The 5-year survival rate of patients with locally advanced esophageal cancer is still low after neoadjuvant therapy plus esophagectomy, and additional adjuvant treatment may be required. Some studies have shown that patients can still benefit from adjuvant chemotherapy (AC) despite its toxic and side effects. This study was designed to explore which patients could benefit from AC. Methods: A retrospective cohort study based on patients who received neoadjuvant therapy plus esophagectomy with complete survival information between December 2014 and November 2020 was conducted. The inclusion criteria were as follows: esophageal cancer was diagnosed by pathological biopsy; neoadjuvant chemotherapy; neoadjuvant chemoradiotherapy; R0 resection. The exclusion criteria were as follows: neoadjuvant chemotherapy combined with targeted therapy or immunotherapy; adjuvant radiotherapy, adjuvant chemoradiotherapy, immunotherapy, or targeted therapy; dead within 90 days of surgery; nonradical (R1/R2) resection; one cycle of postoperative chemotherapy. Patients were divided into AC group (AC) and non-AC group [ AC(-)] according to whether AC was performed. We obtained the tumor recurrence and survival status of the patients through inpatient medical records, outpatient electronic medical records, and telephone follow-up of the First Affiliated Hospital of Zhengzhou University. Overall survival (OS) and recurrence-free survival (RFS) were investigated as the outcome measures via KaplanMeier curves and Cox analyses. Results: In total, 318 patients were enrolled, among which 214 patients received AC while the other 104 patients did not [AC(-)]. There were significant differences in age and lymph nodes dissected between patients who received AC and those who did not receive AC (P<0.05). Survival curves were plotted using the Kaplan-Meier method, and in the overall group and subgroup, AC was beneficial for OS but not for RFS. In the overall group, sex (P= 0.027) and age (P=0.027) were independent prognostic factors for OS. Subgroup multivariate Cox proportional hazards analysis showed that age (P=0.026) and AC (P=0.023) were independent prognostic factors for patients. Conclusions: For patients with locally advanced esophageal cancer who have residual disease after surgery, adjuvant therapy after neoadjuvant chemoradiotherapy and surgery may be a better treatment.

Leptomeningeal metastasis (LM) is one of the most serious complications of advanced non-small cell lung cancer (NSCLC) and lacks standard treatment. Patients with LM often have a poor prognosis. Here, we report a 51-year-old man diagnosed as advanced lung adenocarcinoma and gene sequencing indicated no sensitive driver gene mutation. Pemetrexed and cisplatin plus bevacizumab was administered as first-line therapy. He received pembrolizumab plus nabpaclitaxel as second-line therapy and developed neurological symptoms soon. Later, he was diagnosed LM by cerebrospinal fluid (CSF) cytology and gene sequencing of lung tissue rebiopsy demonstrated epidermal growth factor receptor (EGFR) sensitive mutation. The patient received high-dose (160mg) osimertinib therapy but still could not tolerate severe neurological symptoms and developed cardiac adverse event. After that, standard-dose (80mg) osimertinib plus anlotinib was administered and this treatment regimen resulted in the alleviation of neurological symptoms. As the recent follow up, the curative effect was evaluated stable disease (SD) and the patient gained a progression-free survival (PFS) of more than 15 months. We report this successful salvage therapy of osimertinib plus anlotinib in an advanced lung adenocarcinoma patient who developed LM after failure on previous treatment until EGFR mutation was confirmed through rebiopsy.

Genome alteration signatures reflect recurring patterns caused by distinct endogenous or exogenous mutational events during the evolution of cancer. Signatures of single base substitution (SBS) have been extensively studied in different types of cancer. Copy number alterations are important drivers for the progression of multiple cancer. However, practical tools for studying the signatures of copy number alterations are still lacking. Here, a user-friendly open source bioinformatics tool “sigminer” has been constructed for copy number signature extraction, analysis and visualization. This tool has been applied in prostate cancer (PC), which is particularly driven by complex genome alterations. Five copy number signatures are identified from human PC genome with this tool. The underlying mutational processes for each copy number signature have been illustrated. Sample clustering based on copy number signature exposure reveals considerable heterogeneity of PC, and copy number signatures show improved PC clinical outcome association when compared with SBS signatures. This copy number signature analysis in PC provides distinct insight into the etiology of PC, and potential biomarkers for PC stratification and prognosis.

Wu, Kai MM; Wei, Li MM; Fu, Yifan MM; Zeng, Daxiong MD; Wang, Changguo MD; Jiang, Junhong MD Author Information

Noncoding DNA sequences occupy more than 98% of the human genome; however, few cancer noncoding drivers have been identified compared with cancer coding drivers, probably because cancer noncoding drivers have a distinct mutation pattern due to the distinct function of noncoding DNA. Here we performed pan-cancer whole genome mutation analysis to screen for functional noncoding mutations that influence protein factor binding. Recurrent mutations were identified in the promoter of CDC20 gene. These CDC20 promoter hotspot mutations disrupt the binding of ELK4 transcription repressor, lead to the up-regulation of CDC20 transcription. Physiologically ELK4 binds to the unmutated hotspot sites and is involved in DNA damage-induced CDC20 transcriptional repression. Overall, our study not only identifies a detailed mechanism for CDC20 gene deregulation in human cancers but also finds functional noncoding genetic alterations, with implications for the further development of function-based noncoding driver discovery pipelines.

BACKGROUND:Signet ring cell carcinoma (SRC) is a rare pathological subtype of mucinous adenocarcinoma (AC). Clinical features, prognosis, and especially treatment methods between SRC and AC of the esophagus remain controversial. Thus, we conducted this study to explore the differences in clinicopathological characteristics and treatment modalities between SRC and AC of the esophagus.METHODS:A retrospective cohort study based on the Surveillance, Epidemiology, and End Results (SEER) program database was conducted. Patients diagnosed with SRC or AC not otherwise specified (NOS) were selected between 2004 and 2018. We investigated the prognosis of SRC and AC in terms of overall survival (OS). A subgroup analysis was performed according to the stage and different treatment methods.RESULTS:A total of 24,987 patients were enrolled, including 1,147 with SRC and 23,840 with AC. In the multivariate Cox analysis of the whole cohort, SRC, tumor site, differentiation, metastases, American Joint Committee on Cancer (AJCC) 6th edition staging, treatment, tumor size, lymph nodes examined, and positive lymph nodes were independent risk factors. The results of the subgroup analysis showed that surgery alone was associated with better OS for AC at the early stage, but was not significantly different for SRC (P=0.896). Surgery plus adjuvant therapy was the best treatment for SRC and AC at the late stage. In the multivariate Cox analysis, the treatment of surgery plus adjuvant therapy had a tendency towards better OS at the early stage [hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.39-1.1, P=0.08].CONCLUSIONS:SRC is an independent risk factor, with a higher grade of differentiation, later stage, larger tumor size, more positive lymph nodes, and poorer prognosis compared with AC. Surgery plus adjuvant therapy seems to be useful for SRC at the early stage, but further research is needed.

Background: Circular RNAs (circRNAs) act pivotal roles in the progression of multiple malignancies. However, the underlying mechanisms by which hsa_circ_0007031 (circTUBGCP3) contributes to lung adenocarcinoma (LAC) remain largely unknown. Methods: The association of circTUBGCP3 expression with clinicopathological characteristics and prognosis in patients with LAC was determined by RT-qPCR and fluorescence in situ hybridization. The in vitro functional experiments as well as a subcutaneous tumorigenesis model were executed to estimate the role of circTUBGCP3 in LAC cells. The interaction between circTUBGCP3 and miR-885-3p was confirmed by RNA immunoprecipitation, luciferase gene report and RT-qPCR assays. The effects of circTUBGCP3 on miR-885-3p-mediated Wnt10b/β-catenin signaling were evaluated by Western blot. Results: The upregulation of circTUBGCP3 or downregulation of miR-885-3p was associated with the pathological stage and poor survival in patients with LAC. Restored expression of circTUBGCP3 facilitated the growth and invasion of LAC cells, but knockdown of circTUBGCP3 harbored the opposite effects . In mechanism, circTUBGCP3 could act as a sponge of miR-885-3p, which suppressed the cell proliferation and colony formation and attenuated the tumor-promoting effects of circTUBGCP3. Wnt10b as a target of miR-885-3p could be upregulated be circTUBGCP3 and indicate poor survival in patient with LAC. Conclusions: Our findings demonstrated that circTUBGCP3 promoted LAC progression by sponging miR-885-3p, and might represent a prognostic factor for LAC.