Targeting of vulnerabilities of drug-tolerant persisters identified through functional genetics delays tumor relapse.

Drug-tolerant persisters (DTPs) are a rare subpopulation of cells within a tumor that can survive therapy through nongenetic adaptive mechanisms to develop relapse and repopulate the tumor following drug withdrawal. Using a cancer cell line with an engineered suicide switch to kill proliferating cells, we perform both genetic screens and compound screens to identify the inhibition of bromodomain and extraterminal domain (BET) proteins as a selective vulnerability of DTPs. BET inhibitors are especially detrimental to DTPs that have reentered the cell cycle (DTEPs) in a broad spectrum of cancer types. Mechanistically, BET inhibition induces lethal levels of ROS through the suppression of redox-regulating genes highly expressed in DTPs, including GPX2, ALDH3A1, and MGST1. In vivo BET inhibitor treatment delays tumor relapse in both melanoma and lung cancer. Our study suggests that combining standard of care therapy with BET inhibitors to eliminate residual persister cells is a promising therapeutic strategy.

Paradoxical activation of oncogenic signaling as a cancer treatment strategy.

Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress-response programs that counteract the inherent toxicity of such aberrant signaling. While inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of Protein Phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells. Genetic and compound screens identify combined inhibition of PP2A and WEE1 as synergistic in multiple cancer models by collapsing DNA replication and triggering premature mitosis followed by cell death. This combination also suppressed the growth of patient-derived tumors in vivo. Remarkably, acquired resistance to this drug combination suppressed the ability of colon cancer cells to form tumors in vivo. Our data suggest that paradoxical activation of oncogenic signaling can result in tumor suppressive resistance.

LCP1 knockdown in monocyte-derived macrophages: mitigating ischemic brain injury and shaping immune cell signaling and metabolism.

Rationale: Ischemic stroke poses a significant health burden with limited treatment options. Lymphocyte Cytosolic Protein 1 (LCP1) facilitates cell migration and immune responses by aiding in actin polymerization, cytoskeletal rearrangements, and phagocytosis. We have demonstrated that the long non-coding RNA (lncRNA) Maclpil silencing in monocyte-derived macrophages (MoDMs) led to LCP1 inhibition, reducing ischemic brain damage. However, the role of LCP1 of MoDMs in ischemic stroke remains unknown. Methods and Results: We investigated the impact of LCP1 on ischemic brain injury and immune cell signaling and metabolism. We found that knockdown of LCP1 in MoDMs demonstrated robust protection against ischemic infarction and improved neurological behaviors in mice. Utilizing the high-dimensional CyTOF technique, we demonstrated that knocking down LCP1 in MoDMs led to a reduction in neuroinflammation and attenuation of lymphopenia, which is linked to immunodepression. It also showed altered immune cell signaling by modulating the phosphorylation levels of key kinases and transcription factors, including p-PLCg2, p-ERK1/2, p-EGFR, p-AKT, and p4E-BP1 as well as transcription factors like p-STAT1, p-STAT3, and p-STAT4. Further bioinformatic analysis indicated that Akt and EGFR are particularly involved in fatty acid metabolism and glycolysis. Indeed, single-cell sequencing analysis confirmed that enrichment of fatty acid and glycolysis metabolism in Lcp1high monocytes/macrophages. Furthermore, Lcp1high cells exhibited enhanced oxidative phosphorylation, chemotaxis, migration, and ATP biosynthesis pathways. In vitro experiments confirmed the role of LCP1 in regulating mitochondrial function and fatty acid uptake. Conclusions: These findings contribute to a deeper understanding of LCP1 in the context of ischemic stroke and provide valuable insights into potential therapeutic strategies targeting LCP1 and metabolic pathways, aiming to attenuating neuroinflammation and lymphopenia.

Loss of hepatic FTCD promotes lipid accumulation and hepatocarcinogenesis by upregulating PPARγ and SREBP2.

Background & Aims: Exploiting key regulators responsible for hepatocarcinogenesis is of great importance for the prevention and treatment of hepatocellular carcinoma (HCC). However, the key players contributing to hepatocarcinogenesis remain poorly understood. We explored the molecular mechanisms underlying the carcinogenesis and progression of HCC for the development of potential new therapeutic targets. Methods: The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) and Genotype-Tissue Expression (GTEx) databases were used to identify genes with enhanced expression in the liver associated with HCC progression. A murine liver-specific Ftcd knockout (Ftcd-LKO) model was generated to investigate the role of formimidoyltransferase cyclodeaminase (FTCD) in HCC. Multi-omics analysis of transcriptomics, metabolomics, and proteomics data were applied to further analyse the molecular effects of FTCD expression on hepatocarcinogenesis. Functional and biochemical studies were performed to determine the significance of loss of FTCD expression and the therapeutic potential of Akt inhibitors in FTCD-deficient cancer cells. Results: FTCD is highly expressed in the liver but significantly downregulated in HCC. Patients with HCC and low levels of FTCD exhibited worse prognosis, and patients with liver cirrhosis and low FTCD levels exhibited a notable higher probability of developing HCC. Hepatocyte-specific knockout of FTCD promoted both chronic diethylnitrosamine-induced and spontaneous hepatocarcinogenesis in mice. Multi-omics analysis showed that loss of FTCD affected fatty acid and cholesterol metabolism in hepatocarcinogenesis. Mechanistically, loss of FTCD upregulated peroxisome proliferator-activated receptor (PPAR)γ and sterol regulatory element-binding protein 2 (SREBP2) by regulating the PTEN/Akt/mTOR signalling axis, leading to lipid accumulation and hepatocarcinogenesis. Conclusions: Taken together, we identified a FTCD-regulated lipid metabolic mechanism involving PPARγ and SREBP2 signaling in hepatocarcinogenesis and provide a rationale for therapeutically targeting of HCC driven by downregulation of FTCD. Impact and implications: Exploiting key molecules responsible for hepatocarcinogenesis is significant for the prevention and treatment of HCC. Herein, we identified formimidoyltransferase cyclodeaminase (FTCD) as the top enhanced gene, which could serve as a predictive and prognostic marker for patients with HCC. We generated and characterised the first Ftcd liver-specific knockout murine model. We found loss of FTCD expression upregulated peroxisome proliferator-activated receptor (PPAR)γ and sterol regulatory element-binding protein 2 (SREBP2) by regulating the PTEN/Akt/mTOR signalling axis, leading to lipid accumulation and hepatocarcinogenesis, and provided a rationale for therapeutic targeting of HCC driven by downregulation of FTCD.

Comprehensive analysis of prognostic value and immunotherapy prospect of brain cytoplasmic RNA1 in hepatocellular carcinoma.

BACKGROUND: The expression of brain cytoplasmic RNA1 (BCYRN1) is linked to the clinicopathology and prognosis of several types of cancers, among which hepatocellular carcinoma (HCC) is one of the most frequent types of cancer worldwide. AIM: To explore the prognostic value and immunotherapeutic potential of BCYRN1 in HCC by bioinformatics and meta-analysis. METHODS: Information was obtained from the Cancer Genome Atlas database. First, the correlation between BCYRN1 expression and prognosis and clinicopathologic characteristics of HCC patients was explored. Univariate and multivariate regression analyses were employed to examine the relationship between BCYRN1 and HCC prognosis. Secondly, potential functions and pathways were explored by means of enrichment analysis of differentially-expressed genes. The relationships between BCYRN1 expression and tumor microenvironment, immune cell infiltration, immune checkpoint, drug sensitivity and immunotherapy effect were also investigated. Finally, three major databases were searched and used to conduct a meta-analysis on the relationship between BCYRN1 expression and patient prognosis. RESULTS: BCYRN1 expression was significantly higher in HCC compared to normal tissues and was linked to a poor prognosis and clinicopathological characteristics. Enrichment analysis showed that BCYRN1 regulates the extracellular matrix and transmission of signaling molecules, participates in the metabolism of nutrients, such as proteins, and participates in tumor-related pathways. BCYRN1 expression was linked to the tumor microenvironment, immune cell infiltration, drug sensitivity and the efficacy of immunotherapy. Furthermore, the meta-analysis in this study showed that BCYRN1 overexpression was related to a worse outcome in HCC patients. CONCLUSION: Overexpression of BCYRN1 relates to poor prognosis and may be a potential prognostic factor and immunotherapeutic target in HCC.

Preliminary investigation and application of a modified objects memory test in perioperative cognitive evaluation.

Objective: To investigate the applicability of a modified verbal learning test redesigned from the memory subtest of the Syndrom Kurztest (SKT) in perioperative cognitive evaluation. Methods: Patients receiving elective herniorrhaphy and their accompanying family members (set as normal controls), 55-75 years old, were randomly divided into two groups. The two groups received the self-made objects memory test derived from the SKT (SMOT) SMOT or a traditional auditory verbal learning test (AVLT). The cognitive evaluation was administered at the bedside on the day before surgery and the second day after surgery. Results: The SMOT test was administered to 121 subjects, while 107 patients received the AVLT test. After confirming that there was no significant difference in cognitive function between patients and their family members, the results of the SMOT and AVLT tests were compared. The results showed that the "low-score" ratio of the SMOT was significantly lower than that of the AVLT test (P < 0.05), and the influencing factors of the SMOT were less than those of the AVLT test. However, the learning effect of the SMOT was more significant (P < 0.05). Conclusion: This study preliminarily confirms that the SMOT has better applicability to elderly Chinese individuals than AVLT in perioperative cognitive evaluation, but its learning effect should be noted.

Rational combinations of targeted cancer therapies: background, advances and challenges.

Over the past two decades, elucidation of the genetic defects that underlie cancer has resulted in a plethora of novel targeted cancer drugs. Although these agents can initially be highly effective, resistance to single-agent therapies remains a major challenge. Combining drugs can help avoid resistance, but the number of possible drug combinations vastly exceeds what can be tested clinically, both financially and in terms of patient availability. Rational drug combinations based on a deep understanding of the underlying molecular mechanisms associated with therapy resistance are potentially powerful in the treatment of cancer. Here, we discuss the mechanisms of resistance to targeted therapies and how effective drug combinations can be identified to combat resistance. The challenges in clinically developing these combinations and future perspectives are considered.

Advances in the application of robotic surgical systems to gastric cancer: A narrative review.

Gastric cancer is one of the common malignant tumors in the gastrointestinal tract, and surgery is currently an important treatment for progressive gastric cancer. With the development of technology, the simultaneous maturation of artificial intelligence (AI), fifth-generation (5G) telecommunication networks and the internet of things (IOT) has brought significant efficacy and new opportunities for the surgical treatment of gastric malignancies. The combination of 5G network and remote surgical robotic system is the future trend of radical gastric cancer surgery, and the "unmanned" treatment mode of fully automated robotic gastric cancer radical surgery will be realized soon.

Sustained activation of EGFR-ERK1/2 signaling limits the response to tigecycline-induced mitochondrial respiratory deficiency in liver cancer.

BACKGROUND: Identification of tumor dependencies is important for developing therapeutic strategies for liver cancer. METHODS: A genome-wide CRISPR screen was performed for finding critical vulnerabilities in liver cancer cells. Compounds screen, RNA sequencing, and human phospho-receptor tyrosine kinase arrays were applied to explore mechanisms and search for synergistic drugs. FINDINGS: We identified mitochondrial translation-related genes associated with proliferation for liver cancer cells. Tigecycline induced deficiency of respiratory chain by disturbing mitochondrial translation process and showed therapeutic potential in liver cancer. For liver cancer cells extremely insensitive to tigecycline, a compounds screen was applied to identify MEK inhibitors as synergistic drugs to tigecycline-insensitive liver cancer cells. Mechanistically, sustained activation of EGFR-ERK1/2-MYC cascade conferred the insensitivity to tigecycline, which was mediated by enhanced secretion of EREG and AREG. Moreover, glycolytic enzymes, such as HK2 and PKM2 were upregulated to stimulate glycolysisin a MYC-dependent manner. Tigecycline induced respiratory chain deficiency in combination with cutting off EGFR-ERK1/2-MYC cascade by MEK inhibitors or EGFR inhibitors, resulting in decrease of both oxidative phosphorylation and glycolysis in liver cancer cells. INTERPRETATION: Our study proved that blocking EGFR-ERK1/2-MYC cascade combined with tigecycline could be a potential therapeutic strategy for liver cancer. FUNDING: This work was funded by grants from the National Natural Science Foundation of China (82073039,82222047, 81920108025), Program of Shanghai Academic/Technology Research Leader (22XD1423100), Shanghai Municipal Science and Technology Project (20JC1411100), 111 Project (B21024), Innovative Research Team of High-level Local Universities in Shanghai (SHSMU-ZDCX20212700, SHSMU-ZDCX20210802) and Shanghai Jiao Tong University School of Medicine (YG2019GD01).

cFLIP suppression and DR5 activation sensitize senescent cancer cells to senolysis.

Senolytics, drugs that kill senescent cells, have been proposed to improve the response to pro-senescence cancer therapies; however, this remains challenging due to a lack of broadly acting senolytic drugs. Using CRISPR/Cas9-based genetic screens in different senescent cancer cell models, we identify loss of the death receptor inhibitor cFLIP as a common vulnerability of senescent cancer cells. Senescent cells are primed for apoptotic death by NF-κB-mediated upregulation of death receptor 5 (DR5) and its ligand TRAIL, but are protected from death by increased cFLIP expression. Activation of DR5 signaling by agonistic antibody, which can be enhanced further by suppression of cFLIP by BRD2 inhibition, leads to efficient killing of a variety of senescent cancer cells. Moreover, senescent cells sensitize adjacent non-senescent cells to killing by DR5 agonist through a bystander effect mediated by secretion of cytokines. We validate this 'one-two punch' cancer therapy by combining pro-senescence therapy with DR5 activation in different animal models.

The application of enhanced recovery after surgery in minimally invasive gastrectomy for gastric cancer: a meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed to investigate the efficacy and safety of enhanced recovery after surgery (ERAS) for patients with gastric cancer undergoing minimally invasive surgery (MIS). METHODS: We searched the PubMed, Cochrane Library, Web of Science, Embase, CNKI, VIP, WanFang, and CBM for relevant RCTs from the database inception until December 2021, for studies that compared the ERAS and traditional care (TC) in MIS for gastric cancer. RESULTS: A total of 25 RCTs comprising 2809 patients were included in this study. When compared with the traditional care TC group, the ERAS group had a shorter postoperative hospital stay [MD = -1.88,95%CI (-2.22, -1.55), P < 0.00001] and an earlier time at first postoperative flatus [MD = -18.12,95%CI (-21.45,-14.80), P < 0.00001] along with lower medical costs [SMD = -0.64, 95% CI (-0.85, -0.43), P < 0.00001] and an overall reduction in postoperative complication rates [RR = 0.55, 95% CI (0.44, 0.69), P < 0.00001]. However, the difference in the readmission rates    was not significant. CONCLUSIONS: ERAS can shorten the postoperative hospital stay, hasten the first postoperative flatus and reduce medical costs and overall postoperative complication rate without increasing readmission rates. Therefore, the ERAS protocol is preferable for gastric cancer patients undergoing MIS.

Clinicopathological Significance and Prognostic Values of Long Noncoding RNA BCYRN1 in Cancer Patients: A Meta-Analysis and Bioinformatics Analysis.

Background: Although combination therapies have substantially improved the clinical outcomes of cancer patients, the prognosis and early diagnosis remain unsatisfactory. As a result, it is critical to look for novel indicators linked to cancer. Despite a number of recent studies indicating that the lncRNA brain cytoplasmic RNA1(BCYRN1) may be a potential predictive biomarker in cancer patients, BCYRN1's prognostic value is still being debated. Methods: We utilized PubMed, Embase, Web of Science, and the Cochrane Library to search for studies related to BCYRN1 until October 2021. Valid data were extracted after determining the articles according to the inclusion and exclusion criteria, and forest plots were made using Stata software. We used hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals to evaluate the relationship between abnormal BCYRN1 expression and patient prognosis and clinicopathological characteristics. Results: Meta-analysis revealed that increased BCYRN1 expression was associated with both overall tumor survival (OS; HR = 1.84, 95% CI 1.51-2.25, p < 0.0001) and disease-free survival (DFS; HR = 1.65, 95% CI 1.20-2.26, p=0.002). Furthermore, a strong association was discovered between increased BCYRN1 expression and tumor invasion depth (OR = 2.11, 95% CI 1.49-2.99, p=0.000), clinical stage (OR = 2.52, 95% CI 1.18-5.37, p=0.017), and distant tumor metastasis (OR = 4.19, 95% CI 1.45-12.05, p=0.008). Conclusions: We found that high BCYRN1 expression was associated with poor survival prognosis and aggressive clinicopathological characteristics in various cancers, indicating that it is a potential prognostic indicator as well as a therapeutic target. Further research is needed on pan-cancer cohorts to determine the clinical relevance of BCYRN1 in distinct cancer types.

FOXP4-AS1 May be a Potential Prognostic Biomarker in Human Cancers: A Meta-Analysis and Bioinformatics Analysis.

Background: Cancer is one of the leading causes of death worldwide. Early diagnosis can significantly lower cancer-related mortality. Studies have shown that the lncRNA Forkhead box P4 antisense RNA 1 (FOXP4-AS1) is aberrantly expressed in various solid tumors. A meta-analysis was performed to evaluate the correlation of FOXP4-AS1 with the prognosis of cancer patients and determine the clinical value of FOXP4-AS1 as a potential diagnostic marker. Methods: Correlational studies from the Web of Science, Embase, OVID, Cochrane and PubMed databases were screened (up to April 1, 2021). Meta-analysis was performed using Stata SE12.0 software. Results: Eleven original studies with 1,332 patients who were diagnosed with a solid cancer (nasopharyngeal carcinoma, hepatocellular carcinoma, colorectal cancer, gastric cancer, osteosarcoma, mantle cell lymphoma, prostate cancer, and pancreatic ductal adenocarcinoma) were included in the meta-analysis. High expression of FOXP4-AS1 was correlated with poor overall survival (OS) (HR = 1.77, 95% CI 1.29-2.44, P < 0.001) and shorter disease-free survival (DFS) (HR = 1.66, 95% CI 1.01-2.72, P = 0.044). Subgroup analysis based on sample size, follow-up time and Newcastle-Ottawa Scale (NOS) score revealed significant differences between FOXP4-AS1 levels and OS (P < 0.05). However, the expression level of FOXP4-AS1 was not significantly correlated with the OS of gastric cancer patients (P = 0.381). High expression of FOXP4-AS1 was predictive of a larger tumor size (OR = 3.82, 95% CI 2.3-6.3, P < 0.001). Conclusions: Overexpression of FOXP4-AS1 correlates with poor prognosis of cancer patients, and is a potential prognostic biomarker and therapeutic target. Systematic Review Registration: PROSPERO, identifier CRD42021245267.

Comparative efficacy and safety of local palliative therapeutics for unresectable malignant biliary obstruction: a Bayesian network meta-analysis.

BACKGROUND: Both radiofrequency ablation (RFA), photodynamic therapy (PDT), and biliary stent alone are common local palliative therapies for unresectable malignant biliary obstruction (MBO), but the best modality is uncertain. RESEARCH DESIGN AND METHODS: Embase, Cochrane Library, PubMed, and Web of Science were systematically searched up to 30 January 2022, for eligible studies that compared either two or all modalities in unresectable MBO. RESULTS: Thirty-three studies with 2974 patients were included in this study. The PDT+Stent and RFA+Stent groups had better overall survival and longer mean survival time than Stent alone (all P < 0.05). Moreover, patients with RFA+Stent demonstrated better mean duration of stent patency (MD: 2.0, 95%CI,1.1 to 2.8, P < 0.05) than Stent alone. The three modalities had similar postoperative mild bleeding, cholangitis, and pancreatitis (all P ≥ 0.05). According to network ranking, PDT+Stent was most likely to provide better survival, RFA+Stent was most likely to maintain stent patency. CONCLUSIONS: RFA or PDT plus biliary stent is effective and safe local palliative therapy for unresectable MBO, but the current studies cannot absolutely determine which modality is the best. We should offer patients the most appropriate treatment according to the advantage of each therapy and the patient's performance status.

Local palliative therapies for unresectable malignant biliary obstruction: radiofrequency ablation combined with stent or biliary stent alone? An updated meta-analysis of nineteen trials.

BACKGROUND: Recently, there has been a burgeoning interest in radiofrequency ablation combined with stent (RFA + Stent) for unresectable malignant biliary obstruction (MBO). This study aimed to perform a meta-analysis to evaluate the efficacy and safety of RFA + Stent compared with biliary stent alone. METHODS: We searched PubMed, Cochrane Library, Embase, and Web of Science databases from their inception dates to June 20, 2021, for studies that compared RFA + Stent and stent alone for unresectable MBO. The main outcomes were survival, patency, and adverse effects. All meta-analyses were calculated using the random-effects model. RESULTS: A total of 19 studies involving 1946 patients were included in this study. Compared with stent alone, RFA + Stent was significantly associated with better overall survival (HR 0.55; 95% CI 0.48, 0.63; P < 0.00001), longer mean survival time (SMD 2.20; 95% CI 1.17, 3.22; P < 0.0001), longer mean stent patency time (SMD 1.37; 95% CI 0.47, 2.26; P = 0.003), higher stent patency at 6 months (OR 2.82; 95% CI 1.54, 5.18; P = 0.0008). The two interventions had similar incidence of postoperative abdominal pain (OR 1.29; 95% CI 0.94, 1.78; P = 0.11), mild bleeding (OR 1.28; 95% CI 0.65, 2.54; P = 0.48), cholangitis (OR 1.09; 95% CI 0.76, 1.55; P = 0.65), pancreatitis (OR 1.39; 95% CI 0.82, 2.38; P = 0.22). Furthermore, the serum bilirubin levels and stricture diameter after operations were significantly alleviated than before operations, but the degree of alleviation between the two groups were not significantly different (all P > 0.05). CONCLUSION: Although the alleviation of serum bilirubin and stricture diameter did not differ between the two interventions, RFA + Stent can significantly improve the survival and stent patency with comparable procedure-related adverse events than stent alone. Thus, RFA + Stent should be recommended as an attractive alternative to biliary stent alone for patients with unresectable MBO.

Sult2b1 deficiency exacerbates ischemic stroke by promoting pro-inflammatory macrophage polarization in mice.

Rationale: Stroke is a leading causes of human death worldwide. Ischemic damage induces the sterile neuroinflammation, which directly determines the recovery of patients. Lipids, a major component of the brain, significantly altered after stroke. Cholesterol sulfate, a naturally occurring analog of cholesterol, can directly regulate immune cell activation, indicating the possible involvement of cholesterol metabolites in neuroinflammation. Sulfotransferase family 2b member 1 (Sult2b1) is the key enzyme that catalyzes the synthesis of cholesterol sulfate. This study aimed to investigate the function of Sult2b1 and cholesterol sulfate in the neuroinflammation after ischemic stroke. Methods and Results: Sult2b1-/- and wild-type mice were subjected to transient middle cerebral artery occlusion. Our data showed that Sult2b1-/- mice had larger infarction and worse neurological scores. To determine whether immune cells were involved in the worsening stroke outcome in Sult2b1-/- mice, bone marrow transplantation, immune cell depletion, and adoptive monocyte transfer were performed. Combined with CyTOF and immunofluorescence techniques, we demonstrated that after stroke, the peripheral monocyte-derived macrophages were the dominant cell type promoting the pro-inflammatory status in Sult2b1-/-mice. Using primary bone marrow-derived macrophages, we showed that cholesterol sulfate could attenuate the pro-inflammatory polarization of macrophages under both normal and oxygen-glucose deprivation conditions by regulating the levels of nicotinamide adenine dinucleotide phosphate (NADPH), reactive oxygen species (ROS), and activating the AMP-activated protein kinase (AMPK) - cAMP responsive element-binding protein (CREB) signaling pathway. Conclusions:Sult2b1-/- promoted the polarization of macrophages into pro-inflammatory status. This trend could be attenuated by adding cholesterol sulfate, which promotes the polarization of macrophages into anti-inflammatory status by metabolic regulation. In this study, we established an inflammation-metabolism axis during the macrophage polarization after ischemic stroke.

Clinicopathological and Prognostic Significance of Long Non-coding RNA MIAT in Human Cancers: A Review and Meta-Analysis.

Background: Although the treatment of cancer has made evident progress, its morbidity and mortality are still high. A tumor marker is a critical indicator for early cancer diagnosis, and timely cancer detection can efficiently help improve the prognosis of patients. Therefore, it is necessary to identify novel markers associated with cancer. LncRNA myocardial infarction associated transcript (MIAT) is a newly identified tumor marker, and in this study, we aimed to explore the relationship between MIAT and clinicopathological features and patient prognosis. Methods: We searched PubMed, Embase, Web of Science, and The Cochrane Library from inception to September 2020 to identify correlational studies. Then, we extracted valid data and used Stata software to make forest plots. We used the hazard ratio (HR) or odds ratio (OR) with 95% CI to evaluate the relationship between aberrant expression of MIAT and patients' prognosis and clinicopathological features. Results: The study included 21 studies, containing 2,048 patients. Meta-analysis showed that overexpression of lncRNA MIAT was associated with poor overall survival (OS) (HR = 1.60, 95% CI, 1.31-1.96, p < 0.001). In addition, high expression of MIAT could forecast tumor size (OR = 2.26, 95% CI 1.34-3.81, p = 0.002), distant metastasis (OR = 2.54, 95% CI 1.84-3.50, p < 0.001), TNM stage (OR = 2.38, 95% CI 1.36-4.18, p = 0.002), lymph node metastasis (OR = 2.59, 95% CI 1.25-5.36, p = 0.011), and the degree of differentiation (OR = 2.65, 95% CI 1.54-4.58, p < 0.001). However, other clinicopathological features, including age (OR = 1.07, 95% CI 0.87-1.32, p = 0.516), gender (OR = 0.95, 95% CI 0.77-1.19, p = 0.668), and histology (OR = 0.72, 95% CI 0.48-1.10, p = 0.128) were not significantly different from high expression of MIAT. Conclusions: Our study showed that overexpression of MIAT is related to poor overall survival and clinicopathological features. MIAT can be considered a novel tumor marker to help diagnose tumors earlier and improve patient prognosis.