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The involvement of endoplasmic reticulum stress pathways in midazolam-induced apoptosis in Ma-10 cells. Notes: A one-way analysis of variance and least significant difference comparison were performed. MA-10 cells were treated with midazolam (0, 30, and 150 µM) for 3, 6, 12, and 24 hours (hr), respectively. ATF6β (76 kDa), phosphor-IRE1α (110 kDa), IRE1α (130 kDa), XBP1 (28 kDa), and cleaved CASP12 (42 kDa) were detected by Western blot (A). integrated optical densities of aTF6β (B), phosphor-ire1α (C), XBP1 (D), and cleaved CASP12 (E) proteins were normalized with β-actin (43 kDa) in each lane, respectively. *Indicates statistical difference compared to control (C) (P,0.05). P represents the positive control.
Source publication
Purpose:
Midazolam is widely used as a sedative and anesthetic induction agent by modulating the different GABA receptors in the central nervous system. Studies have also shown that midazolam has an anticancer effect on various tumors. In a previous study, we found that midazolam could induce MA-10 mouse Leydig tumor cell apoptosis by activating c...
Citations
... The most common mechanism was the mitochondrial intrinsic pathway [9,12,18,19] and induced apoptosis. [4,20,22,24] Other mechanisms include [14] In Vitro Mouse Leydig Tumour Mouse Leydig Tumour (MA-10) Midazolam Braun et al., 2015 [15] In Vitro Human Neuroblastoma Human Neuroblastoma (SHEP) Midazolam Chen et al., 2016 [16] In Vitro Human Malignant Glioma Malignant glioblastoma T98-MG cells Midazolam So et al., 2016 [17] In [20] In Vitro + In Vivo ...
... the p53 pathway, [17] necrosis, transient receptor potential melastatin (TRPM)7 inhibition, [11,16] S-phase cell cycle arrest, [12] etc. One study [15] did not recognise specific mechanisms by which midazolam reduced the cytotoxicity of temozolomide in neuroblastoma cells. ...
... [28] In this review, midazolam inhibited cancer cell progression in various cancer cell lines; human non-small cell lung cancer (NSCLC) [18,19,22,23] and hepatocellular carcinoma [20,25,26] were the most studied cancer types. Midazolam also suppressed the progression of human T-cell lymphoma and neuroblastoma, [9] oral squamous cell carcinoma and glioblastoma, [10] hypopharyngeal squamous cell carcinoma, [11,13] leukaemia and colon cancer, [12] mouse Leydig tumour, [14,17] neuroglioma, [18] melanoma, [21] pancreatic ductal adenocarcinoma, [24] breast cancer (oestrogen positive), [23] and malignant glioma. [16] Midazolam appeared to inhibit cancer cell proliferation in hypopharyngeal squamous cell carcinoma, leukaemia, colon cancer, neuroglioma, NSCLC, breast, pancreatic, glioblastoma, and hepatocellular carcinoma. ...
Background and Aims
Cancer is a leading cause of mortality worldwide. Despite advancements in cancer management, cancer progression remains a challenge, requiring the development of novel therapies. Midazolam is a commonly used adjunct to anaesthesia care for various surgeries, including cancer. Recently, there has been a growing interest in exploring the potential role of midazolam as an anticancer agent; however, the exact mechanism of this linkage is yet to be investigated thoroughly.
Methods
Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, this systematic review presented aggregated evidence (till November 2022) of the effects of midazolam on cancer progression and survival. All primary research article types where midazolam was administered in vivo or in vitro on subjects with cancers were included. No restrictions were applied on routes of administration or the type of cancer under investigation. Narrative synthesis depicted qualitative findings, whereas frequencies and percentages presented numerical data.
Results
Of 1720 citations, 19 studies were included in this review. All articles were preclinical studies conducted either in vitro (58%, 11/19) or both in vivo and in vitro (42%, 8/19). The most studied cancer was lung carcinoma (21%, 4/19). There are two main findings in this review. First, midazolam delays cancer progression (89%, 17/19). Second, midazolam reduces cancer cell survival (63%, 12/19). The two major mechanisms of these properties can be explained via inducing apoptosis (63%, 12/19) and inhibiting cancer cell proliferation (53%, 10/19). In addition, midazolam demonstrated antimetastatic properties via inhibition of cancer invasion (21%, 4/19), migration (26%, 5/19), or epithelial-mesenchymal transition (5%, 1/19). These anticancer properties of midazolam were demonstrated through different pathways when midazolam was used alone or in combination with traditional cancer chemotherapeutic agents.
Conclusion
This systematic review highlights that midazolam has the potential to impede cancer progression and decrease cancer cell survival. Extrapolation of these results into human cancer necessitates further investigation.
... DEX allows patients to breathe spontaneously during sedation, thereby reducing the risk of respiratory depression [22]. Except for the sedative effects, DEX also exhibits antitumor effects just like morphine [23], propofol [24], midazolam [25], diazepam [26], sufentanil [27], tramadol [28], and many other classic sedative and analgesic drugs. To explore the performance of DEX in HCC, we performed in vitro experiments, and eventually unveiled that DEX suppressed HCC cell development. ...
Accumulating evidence has revealed the role of microRNAs (miRs) in hepatocellular carcinoma (HCC). Dexmedetomidine, a highly selective α 2 -adrenergic agonist, is widely used in perioperative settings for analgesia and sedation. Herein, we aimed to determine whether dexmedetomidine might directly regulate miR-130a/early growth response 1 (EGR1) axis in HCC and explore the related mechanisms. miR-130a and EGR1 expression were determined in HCC tissues and their correlation was evaluated. Human HCC cell line HCCLM3 was selected. Upon the determination of the optimal concentration of dexmedetomidine, HCCLM3 cells were treated with dexmedetomidine, miR-130a- or EGR1-related oligonucleotides or plasmids were transfected into cells to explore their functions in cell biological behaviors. miR-130a and EGR1 levels in cells were tested. The targeting relationship between miR-130a and EGR1 was verified. miR-130a was inhibited while EGR1 was elevated in HCC tissues and they were negatively correlated. EGR1 was targeted by miR-130a. With the increase of dexmedetomidine concentration, HCCLM3 cell viability was correspondingly inhibited, miR-130a expression was elevated and EGR1 expression was decreased. Dexmedetomidine, upregulating miR-130a or downregulating EGR1 inhibited proliferation, invasion and migration, and promoted apoptosis of HCCLM3 cells. MiR-130a upregulation/downregulation enhanced/impaired the effect of dexmedetomidine on cell biological behaviors. Our study provides evidence that raising miR-130a enhances the inhibitory effects of dexmedetomidine on HCC cellular growth via inhibiting EGR1. Thus, miR-130a may be a potential candidate for the treatment of HCC.
... Animal experiments have demonstrated that MDZ can inhibit the ability of animals to exercise and induce muscle relaxation [13]. In addition, many original studies have recently shown that MDZ demonstrates an extraordinary ability to promote apoptosis in several human cancer cells and hinder tumour growth in xenotransplantation mouse models [14]. However, studies on the relationship between MDZ and the tumour immune microenvironment have not been carried out. ...
Background
Midazolam (MDZ) is an anaesthetic that is widely used for anxiolysis and sedation. More recently, MDZ has also been described to be related to the outcome of various types of carcinomas. However, how MDZ influences the progression of hepatocellular carcinoma (HCC) and its effects on the biological function and tumour immune microenvironment of this type of tumour remain unknown.
Methods
The effects of MDZ on the proliferation, invasion, and migration of HCC cell lines were examined in vitro using the Cell Counting Kit 8 (CCK8), 5-ethynyl-2ʹ-deoxyuridine (EdU), Transwell, and wound healing assays. Additionally, western blotting was employed to confirm that PD-L1 was expressed. Chromatin immunoprecipitation-seq (ChIP-seq) analysis was used to pinpoint the transcriptional regulation regions of NF-κB and programmed death-ligand 1 (PD-L1). A C57BL/6 mouse model was used to produce subcutaneous HCC tumors in order to evaluate the in vivo performance of MDZ. Mass spectrometry was also used to assess changes in the tumour immunological microenvironment following MDZ injection.
Results
The HCC-LM3 and Hep-3B cell lines’ proliferation, invasion, and migration were controlled by MDZ, according to the results of the CCK8, EdU, Transwell, and wound healing assays. PD-L1 expression was shown by ChIP-seq analysis to be boosted by NF-κB, and by Western blotting analysis, it was shown that MDZ downregulated the expression of NF-κB. Additionally, in vivo tests revealed that intraperitoneal MDZ injections reduced HCC tumor development and enhanced the effectiveness of anti-PD-1 therapy. The CD45⁺ immune cell proportions were higher in the MDZ group than in the PBS group, according to the mass spectrometry results. Injection of MDZ resulted in a decrease in the proportions of CD4⁺ T cells, CD8⁺ T cells, natural killer (NK) cells, monocytes, Tregs, and M2 macrophages and a rise in the proportion of dendritic cells. Additionally, the concentrations of the cytokines IFN-g and TNF-a were noticeably raised whereas the concentrations of the CD8⁺ T-cell fatigue markers ICOS, TIGIT, and TIM3 were noticeably lowered.
Conclusion
According to this study, MDZ inhibited the progression of HCC by inhibiting the NF-κB pathway and reducing the exhaustion of CD8⁺ T cells. In clinical practice, MDZ combined with anti-PD-1 therapy might contribute to synergistically improving the antitumor efficacy of HCC treatment.
... 14 In addition, Bcl-2 family proteins play different physiological roles for mitochondrial integrity, including Bcl-xL and Bcl-2 multidomain antiapoptotic, Bak and Bax multidomain proapoptotic, and Bmf and Bid BH3-only proapoptotic proteins. 12,15 These proteins could negatively or positively regulate the permeability of mitochondria and the efflux of proteins related to apoptosis. 16,17 It is shown that arsenite trioxide could upregulate BH3-only proapoptotic proteins and downregulate antiapoptotic proteins in myeloma. ...
... Previous studies have shown Bcl-2 family proteins participated in the intrinsic apoptosis pathway and the regulation of mitochondrial integrity. 12,41 To determine the relationship between intrinsic mitochondrial pathway with Bcl-2 family proteins of arsenic-induced apoptosis in MA-10 cells, expression of Bid, Bax, and cytochrome C proteins in mitochondrial and cytosolic fractions were investigated. Results showed that sodium arsenite at 10 μM for 24 h considerably stimulated cytochrome C release in dose-dependent (Figure 2A,B) (p < 0.05) and time-dependent manners ( Figure 3A,B) (p < 0.05), correspondingly. ...
... C efflux. 12,15 It has been reported that arsenic trioxide could inhibit functions of mitochondria of MCF7 breast cancer cells. 48 Arsenic trioxide could also disrupt mitochondrial membrane potential to sensitize radiation therapy in mouse lung carcinoma model. ...
Arsenic compounds have been applied treating acute promyelocytic 1eukemia and solid tumors with brief mechanism investigations. In fact, we have demonstrated that sodium arsenite plus dimethylarsenic acid could activate apoptosis in MA-10 mouse Leydig tumor cells by inducing caspase pathways. However, detail underlying mechanisms how caspase cascade is regulated remains elusive. Therefore, the apoptotic mechanism of sodium arsenite plus dimethylarsenic acid were examined in MA-10 cells in this study. Our results reveal that Fas/FasL protein expressions were stimulated by sodium arsenite plus dimethylarsenic acid in MA-10 cells. In addition, reactive oxygen species (ROS) generation, cytochrome C release, Bid truncation, and Bax translocation were induced in MA-10 cells by arsenic compounds. Moreover, activation of p38, JNK and ERK1/2, MAPK pathways was stimulated while Akt phosphorylated levels and Akt expression were decreased by sodium arsenite plus dimethylarsenic in MA-10 cells. In conclusion, sodium arsenite and dimethylarsenic acid did activate MAPK pathway plus ROS generation, but suppress Akt pathway, to modulate caspase pathway and then induce MA-10 cell apoptosis.
... Indeed, treatment of midazolam (Dormicum ® ), a short-acting BDZ derivative, with anxiolytic, sedative, hypnotic, muscle relaxant, and anticonvulsant effects, is shown to affect cancer cell behavior. Midazolam induces the apoptosis of mouse Leydig tumor cell line [31,32], non-small cell lung carcinoma cell lines (NSCLC) [33], leukemia and colon cancer cells [34], hepatocellular carcinoma cells (HCCs) [34], and lymphoma and neuroblastoma cells [35] as well as inhibiting cancer cell proliferation [31][32][33][34][35][36]. Exposure of these cancer cells to midazolam induces the activation of intrinsic caspase cascade [31][32][33][34]36], down-regulation of phosphorylated ERK [31], anti-apoptosis protein B-cell lymphoma extra-large (BCL-xL), and X-linked inhibitor of apoptosis protein (XIAP) [33]. ...
... Indeed, treatment of midazolam (Dormicum ® ), a short-acting BDZ derivative, with anxiolytic, sedative, hypnotic, muscle relaxant, and anticonvulsant effects, is shown to affect cancer cell behavior. Midazolam induces the apoptosis of mouse Leydig tumor cell line [31,32], non-small cell lung carcinoma cell lines (NSCLC) [33], leukemia and colon cancer cells [34], hepatocellular carcinoma cells (HCCs) [34], and lymphoma and neuroblastoma cells [35] as well as inhibiting cancer cell proliferation [31][32][33][34][35][36]. Exposure of these cancer cells to midazolam induces the activation of intrinsic caspase cascade [31][32][33][34]36], down-regulation of phosphorylated ERK [31], anti-apoptosis protein B-cell lymphoma extra-large (BCL-xL), and X-linked inhibitor of apoptosis protein (XIAP) [33]. ...
... Midazolam induces the apoptosis of mouse Leydig tumor cell line [31,32], non-small cell lung carcinoma cell lines (NSCLC) [33], leukemia and colon cancer cells [34], hepatocellular carcinoma cells (HCCs) [34], and lymphoma and neuroblastoma cells [35] as well as inhibiting cancer cell proliferation [31][32][33][34][35][36]. Exposure of these cancer cells to midazolam induces the activation of intrinsic caspase cascade [31][32][33][34]36], down-regulation of phosphorylated ERK [31], anti-apoptosis protein B-cell lymphoma extra-large (BCL-xL), and X-linked inhibitor of apoptosis protein (XIAP) [33]. The midazolam-induced cancer cell apoptosis can be observed not only in the in vitro model but also in the in vivo animal model [34]. ...
Cancer is one of the leading causes of death worldwide. There are only limited treatment strategies that can be applied to treat cancer, including surgical resection, chemotherapy, and radiotherapy, but these have only limited effectiveness. Developing a new drug for cancer therapy is protracted, costly, and inefficient. Recently, drug repurposing has become a rising research field to provide new meaning for an old drug. By searching a drug repurposing database ReDO_DB, a brief list of anesthetic/sedative drugs, such as haloperidol, ketamine, lidocaine, midazolam, propofol, and valproic acid, are shown to possess anti-cancer properties. Therefore, in the current review, we will provide a general overview of the anti-cancer mechanisms of these anesthetic/sedative drugs and explore the potential underlying signaling pathways and clinical application of these drugs applied individually or in combination with other anti-cancer agents.
... In animal experiments, MZ has reported to damage the exercise ability of animals and cause muscle relaxation [19]. While recently, MZ is reported to induce apoptosis in human cancer cells and block tumor growth in xenotransplantation mice [20], as well as to modulate miRs [21]. Nonetheless, there is no research to verify whether MZ can inhibit HCC cells and regulate miR-217. ...
Background:
Hepatocellular carcinoma (HCC) is a significant cause of human death in the world. Recently, it is found that midazolam can modulate miRs to participate in HCC progression. This research project was designed to elucidate the impacts of midazolam and miR-217 on HCC cell metastasis and apoptosis.
Methods:
Human HCC cell strains (Hep3B and SK-HEP-1) were selected and intervened by midazolam at different concentrations in our research. miR-217-inhibitor intervened in the two HCC cell strains to observe the alterations of cell migration, invasiveness, and apoptosis. The miR-217 level in HCC cells was identified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).
Results:
As midazolam concentration was elevated, Hep3B and SK-HEP-1 viabilities were more obviously suppressed. The 10 μg/mL concentration was selected for analysis since Hep3B and SK-HEP-1 had an IC50 of 10.57 μg/mL and 9.35 μg/m, respectively. The qRT-PCR results showed the decreased of miR-217 in HCC cells, which was enhanced notably by midazolam intervention. Compared with the blank group, the invasiveness and migration (Transwell assay) of miR-217-inhibitor-transfected HCC cells were distinctly enhanced and the apoptosis rate (flow cytometry) was noticeably reduced.
Conclusion:
Midazolam can upregulate miR-217 in HCC cells, thus inhibiting HCC cell metastasis and apoptosis.
... 2,23 Induction of non-apoptotic cell death can result from p53-hetero-knockout in PDAC cell lines. 14 Although recent studies indicate that MDZ modulates not only the cell cycle but also the mitochondrial caspase pathway, endoplasmic reticulum stress, and autophagy to induce apoptosis, 24 downregulation of cyclins/CDKs and the sequential cell-cycle arrest and induction of apoptotic and non-apoptotic cell death could be key mechanisms of MDZ in PDAC cells. ...
Background:
Anaesthesia and perioperative management contribute to long-term outcomes of patients with cancer, including pancreatic ductal adenocarcinoma. We assessed the antitumour, anti-inflammatory, and analgesic effects of midazolam on LSL-KrasG12D/+;Trp53flox/flox;Pdx-1cre/+ transgenic mice with pancreatic ductal adenocarcinoma.
Methods:
Six-week-old transgenic mice were administered midazolam 30 mg kg-1 day-1 p.o. (n=13); midazolam 30 mg kg-1 day-1 with 1-(2-chlorophenyl)-N-methyl-N(1-methylpropyl)-3-isoquinoline carboxamide (PK11195) 3 mg kg-1 day-1 i.p., a peripheral benzodiazepine receptor antagonist (n=10); or vehicle (water; n=14) until the humane endpoint. Cancer-associated pain was evaluated using hunching score and mouse grimace scale. Tumour stage and immuno-inflammatory status were determined histopathologically. Anti-proliferative and apoptotic potentials of midazolam were investigated using mouse pancreatic ductal adenocarcinoma cell lines.
Results:
Midazolam significantly inhibited tumour size and proliferative index of Ki-67 and cyclins in pancreatic ductal adenocarcinoma, which was blocked by administration of PK11195. Local myeloperoxidase+ tumour-associated neutrophils, arginase-1+ M2-like tumour-associated macrophages, and CD11b+Ly-6G+ polymorphonuclear myeloid-derived suppressor cells were reduced by midazolam, which was antagonised by administration of PK11195. Hunching and mouse grimace scale were improved by midazolam, whereas the scores increased with midazolam+PK11195 treatment. Plasma pro-inflammatory cytokines, such as interleukin-6 and CC chemokine ligand (CCL)2, CCL3, and CCL5, were reduced by midazolam, whereas these cytokines increased with PK11195. Midazolam inhibited pancreatic ductal adenocarcinoma proliferation through downregulation of cyclins and cyclin-dependent kinases and induced apoptosis in vitro.
Conclusions:
These results suggest that midazolam inhibits pancreatic ductal adenocarcinoma proliferation and local infiltration of tumour-associated neutrophils, tumour-associated macrophages, and polymorphonuclear myeloid-derived suppressor cells, thereby inhibiting pancreatic ductal adenocarcinoma progression.
... Recently, reports have shown that MDZ is a novel therapeutic agent to treat cancer [23]. Administrated in high doses (100 µM and higher), MDZ has been show to induce apoptosis via activation of the mitochondrial pathway in human lymphoma and neuroblastoma cells [24], or regulated endoplasmic reticulum stress, autophagy, and cell cycle to induce apoptosis in Leydig tumor/progenitor cells [25,26]. However, the detail mechanisms by means of which MDZ is involved in the cancer progression and EMT remain largely unknown. ...
Despite improvements in cancer treatments resulting in higher survival rates, the proliferation and metastasis of tumors still raise new questions in cancer therapy. Therefore, new drugs and strategies are still needed. Midazolam (MDZ) is a common sedative drug acting through the γ-aminobutyric acid receptor in the central nervous system and also binds to the peripheral benzodiazepine receptor (PBR) in peripheral tissues. Previous studies have shown that MDZ inhibits cancer cell proliferation but increases cancer cell apoptosis through different mechanisms. In this study, we investigated the possible anticancer mechanisms of MDZ on different cancer cell types. MDZ inhibited transforming growth factor β (TGF-β)-induced cancer cell proliferation of both A549 and MCF-7 cells. MDZ also inhibited TGF-β-induced cell migration, invasion, epithelial-mesenchymal-transition, and Smad phosphorylation in both cancer cell lines. Inhibition of PBR by PK11195 rescued the MDZ-inhibited cell proliferation, suggesting that MDZ worked through PBR to inhibit TGF-β pathway. Furthermore, MDZ inhibited proliferation, migration, invasion and levels of mesenchymal proteins in MDA-MD-231 triple-negative breast cancer cells. Together, MDZ inhibits cancer cell proliferation both in epithelial and mesenchymal types and EMT, indicating an important role for MDZ as a candidate to treat lung and breast cancers.
... In MDZ has also been reported to have anticancer, neurotoxic, and, on the contrary, neuroprotective effects (26). In several in vitro studies, MDZ has been shown to promote apoptosis and to reduce proliferation in neuroblastoma and mouse Leydig cells (6,16,24). Some other studies have also suggested that MDZ and other anesthetic agents have neurodegenerative effects on brain cells, particularly in the developing human brain (3). Similarly, some animal studies have shown that MDZ leads to learning and memory impairment along with neurodegeneration in the developing rat brain (9). ...
... On the other hand, MDZ has also been suggested to have a role in cell cycle and proliferation. Accordingly, some previous studies have indicated that MDZ may block the cell cycle at the G2/M phase by inhibiting the expression of cyclin A, cyclin B, and cyclin-dependent kinase 1, and may inhibit cell proliferation by blocking the cell cycle at the G0/G1 phase (10,24). ...
Aim:
To investigate the effects of midazolam (MDZ) and thiopental on neonatal and adult rat brains.
Material and methods:
The study included adult and 7-day-old rats that were administered 9 mg/kg of MDZ, 60 mg/kg of thiopental, or both. The Bax, procaspase-3, and caspase-3 levels were assessed using Western Blot analysis and the total oxidative stress index (OSI) values were measured spectrophotometrically.
Results:
The procaspase-3 and caspase-3 levels were 12% and 6% lower in the neonatal MDZ group when compared to the control group. The Bax, procaspase-3, and caspase-3 levels were higher in the neonatal thiopental group by 25%, 4%, and 34%, and in the MDZ group by 16%, 19%, and 43% when compared to the neonatal control group. In the adult rats, the caspase-3 levels were 10 times higher in the MDZ group when compared to the control and thiopental groups. Moreover, the caspase-3 levels were 7 times higher in the adult thiopental group when compared to the control group. The OSI values in the neonatal rats were significantly higher in the neonatal MDZ and neonatal thiopental groups when compared to the control group (p < 0.05). Similarly, the OSI values in the adult rats were significantly higher in the neonatal MDZ and neonatal thiopental groups when compared to the control group (p < 0.05).
Conclusion:
MDZ and thiopental may promote apoptosis and oxidative stress, and thereby result in neurotoxicity, with MDZ showing a greater effect in adults and thiopental showing a greater effect in neonates.
... Interestingly, anesthetics can also inhibit tumor growth by regulating autophagy. So et al. found that midazolam can induce apoptosis of Leydig tumor cells by regulating autophagy [20]. Zhang et al. also found that ropivacaine can inhibit the growth of melanoma [21]. ...
Background: Esophageal carcinoma (ESCA) is a malignant tumor with high invasiveness and mortality. Autophagy has multiple roles in the development of cancer; however, there are limited data on autophagy genes associated with long non-coding RNAs (lncRNAs) in ESCA. The purpose of this study was to screen potential diagnostic and prognostic molecules, and to identify gene co-expression networks associated with autophagy in ESCA.
Methods: We downloaded transcriptome expression profiles from The Cancer Genome Atlas and autophagy-related gene data from the Human Autophagy Database, and analyzed the co-expression of mRNAs and lncRNAs. In addition, the diagnostic and prognostic value of autophagy-related lncRNAs was analyzed by multivariate Cox regression. Furthermore, Kyoto Encyclopedia of Genes and Genomes analysis was carried out for high-risk patients, and enriched pathways were analyzed by gene set enrichment analysis.
Results: The results showed that genes of high-risk patients were enriched in protein export and spliceosome. Based on Cox stepwise regression and survival analysis, we identified seven autophagy-related lncRNAs with prognostic and diagnostic value, with the potential to be used as a combination to predict the prognosis of patients with ESCA. Finally, a co-expression network related to autophagy was constructed.
Conclusion: These results suggest that autophagy-related lncRNAs and the spliceosome play important parts in the pathogenesis of ESCA. Our findings provide new insight into the molecular mechanism of ESCA and suggest a new method for improving its treatment.
