Biology subjects

Hu, K.

Publications and source records attributed to Hu, K..

At least 91 records · Page 5Linked to original sources

bioRxiv2021

Systematic Chromosome Rearrangement Induced by CRISPR-Cas9 Reshapes the Genome and Transcriptome of Human Cells

Chromosome rearrangement plays important roles in development, carcinogenesis and evolution. However, its mechanism and subsequent effects are not fully understood. At present, large-scale chromosome rearrangement has been performed in the simple eukaryote, wine yeast, but the relative research in mammalian cells remains at the level of individual chromosome rearrangement due to technical limitations. In this study, we used CRISPR-Cas9 to target the highly repetitive human endogenous retrotransposons, LINE-1 (L1) and Alu, resulting in a large number of DNA double-strand breaks in the chromosomes. While this operation killed the majority of the cells, we eventually obtained live cell groups. Karyotype analysis and genome re-sequencing proved that we have achieved systematic chromosome rearrangement (SCR) in human cells. The copy number variations (CNVs) of the SCR genomes showed typical patterns that observed in tumor genomes. For example, the most frequent deleted region Chr9p21 containing p15 and p16 tumor suppressor, and the amplified region Chr8q24 containing MYC in tumors were all identified in both SCR cells. The ATAC-seq and RNA-seq further revealed that the epigenetic and transcriptomic landscapes were deeply reshaped by the SCR. Gene expressions related to p53 pathway, DNA repair, cell cycle and apoptosis were greatly altered to facilitate the cell survival under the severe stress induced by the large-scale chromosomal breaks. In addition, we found that the cells acquired CRISPR-Cas9 resistance after SCR by interfering with the Cas9 mRNA. Our study provided a new application of CRISPR-Cas9 and a practical approach for SCR in complex mammalian genomes. HighlightsRepetitive retroelements with large copy numbers were targeted using CRISPR-Cas9 in human cells. Cells survived after their chromosomal DNAs were heavily cleaved and systematic chromosome rearrangement was achieved. Systematic chromosome rearrangement reshaped the genome and transcriptome of the cells.

genomics↗

bioRxiv2021

Radiosynthesis and preclinical evaluation of a carbon-11 labeled PDE7 inhibitor for PET neuroimaging

BackgroundDysfunction of cyclic nucleotide phosphodiesterase 7 (PDE7) has been associated with excess intracellular cAMP concentrations, fueling pathogenic processes that are implicated in neurodegenerative disorders. The aim of this study was to develop a suitable PDE7-targeted positron emission tomography (PET) probe that allows non-invasive mapping of PDE7 in the mammalian brain. MethodsBased on a spiro cyclohexane-1,4-quinazolinone scaffold with known inhibitory properties towards PDE7, we designed and synthesized a methoxy analog that was suitable for carbon-11 labeling. Radiosynthesis was conducted with the respective desmethyl precursor using [11C]MeI. The resulting PET probe, codenamed [11C]26, was evaluated by cell uptake studies, ex vivo biodistribution and radiometabolite studies, as well as in vivo PET experiments in rodents and nonhuman primates (NHP). ResultsTarget compound 26 and the corresponding phenolic precursor were synthesized in 2-3 steps with overall yields of 49.5% and 12.4%, respectively. An inhibitory constant (IC50) of 31 nM towards PDE7 was obtained and no significant interaction with other PDE isoforms were observed. [11C]26 was synthesized in high molar activities (170 - 220 GBq/{micro}mol) with radiochemical yields of 34{+/-}7%. In vitro cell uptake of [11C]26 was 6-7 folds higher in PDE7 overexpressing cells, as compared to the controls, whereas an in vitro specificity of up to 90% was measured. Ex vivo metabolite studies revealed a high fraction of intact parent in the rat brain (98% at 5 min and 75% at 30 min post injection). Considerable brain penetration was further corroborated by ex vivo biodistribution and PET imaging studies - the latter showing heterogenic brain uptake. While marginal specific binding was observed by PET studies in rodents, a moderate, but dose-dependent, blockade was observed in the NHP brain following pretreatment with non-radioactive 26. ConclusionIn this work, we report on the preclinical evaluation of [11C]26 (codename [11C]P7-2104), a PDE7-targeted PET ligand that is based on a spiroquinazolinone scaffold. [11C]26 displayed promising in vitro performance characteristics, a moderate degree of specific binding in PET studies with NHP. Accordingly, [11C]26 will serve as a valuable lead compound for the development of a new arsenal of PDE7-targeted probes with potentially improved in vivo specificity.

neuroscience↗

bioRxiv2021

Accelerating RepeatClassifier Based on Spark and Greedy Algorithm with Dynamic Upper Boundary

1Transposable elements (TEs) represent quantitatively important components of genome sequences (e.g. 90% of the wheat genome), and play important roles in genome organization and evolution. The promotion of unsupervised annotation of transposable elements is of great significance. Classification is an important step in TE annotation, which summarize the information about the type or mechanism for the raw repetitive sequences. RepeatClassifier is a basic homology-based classification tool which compares the TE families to both the Repeat Protein Database (DB) and libraries of RepeatMasker. Unfortunately, RepeatClassifier is inefficient and takes a few days to classify the repetitive sequences of large genomes. Hence, we proposed Spark-based RepeatClassifier (SRC) which uses Greedy Algorithm with Dynamic Upper Boundary (GDUB) for data division and load balancing, and Spark to improve the parallelism of RepeatClassifier. Experimental results show that SRC can not only ensure the same level of accuracy as that of RepeatClassifier, but also achieve 42-88 times of acceleration compared to RepeatClassifier. At the same time, SRC shows excellent parallel performance when dealing with input datasets with unbalanced length distribution. SRC is publicly available at https://github.com/BioinformaticsCSU/SRC.

bioinformatics↗

bioRxiv2021

Extremely bright, near-IR emitting spontaneously blinking fluorophores enable ratiometric multicolor nanoscopy in live cells

New bright, photostable, emission-orthogonal fluorophores that blink without toxic additives are needed to enable multi-color, live-cell, single-molecule localization microscopy (SMLM), especially for experiments that demand ultra-high-resolution live imaging. Here we report the design, synthesis, and biological evaluation of Yale676sb, a photostable, near-IR emitting fluorophore that achieves these goals in the context of an exceptional quantum yield (0.59). When used alongside HMSiR, Yale676sb enables simultaneous, live-cell, two-color SMLM of two intracellular organelles (ER + mitochondria) with only a single laser and no chemical additives.

cell biology↗

bioRxiv2021

CMOS electrochemical imaging arrays for thedetection and classification of microorganisms

Microorganisms account for most of the biodiversity on earth. Yet while there are increasingly powerful tools for studying microbial genetic diversity, there are fewer tools for studying microorganisms in their natural environments. In this paper, we present recent advances in CMOS electrochemical imaging arrays for detecting and classifying microorganisms. These microscale sensing platforms can provide non-optical measurements of cell geometries, behaviors, and metabolic markers. We review integrated electronic sensors appropriate for monitoring microbial growth, and present measurements of single-celled algae using a CMOS sensor array with thousands of active pixels. Integrated electrochemical imaging can contribute to improved medical diagnostics and environmental monitoring, as well as discoveries of new microbial populations.

bioengineering↗

bioRxiv2021

Electrochemical measurements reveal reactive oxygen species in stress granules.

Stress granules (SGs) are membraneless organelles that assemble in the cytoplasm to organize cellular contents and promote rapid adaptation during stress. To understand how SGs contribute to physiological functions, we used electrochemical measurements to detect electroactive species in SGs. With amperometry, we discovered that reactive oxygen species (ROS) are encapsulated inside arseniteinduced SGs, and H2O2 is the main species. The release kinetics of H2O2 from single SGs and the number of H2O2 molecules were quantified. The discovery that SGs contain ROS implicates them as communicators of the cellular stresses rather than a simple end-point. This may explain how SGs regulate cellular metabolism and stress responses. This may also help better understand their cytoprotective functions in pathological conditions associated with SGs such as neurodegenerative diseases, cancers and viral infections.

biochemistry↗

bioRxiv2021

BnaA03.WRKY28, interacting with BnaA09.VQ12, acts as a brake factor of activated BnWRKY33-mediated resistance outburst against Sclerotinia sclerotiorum in Brassica napus

Sclerotinia sclerotiorum causes substantial damage to the growth of Brassica napus (rapeseed) and makes a significant loss of crop yield. The plant innate immune system may be the primary solution to defense against S. sclerotiorum for rapeseed. Here, we identify that BnWRKY33, a transcription factor in the innate immune pathway, can be rapidly phosphorylated and activated by the MAPK cascade after rapeseed is infected with S. sclerotiorum. In the MAPK cascade, activated BnaA03.MKK4 phosphorylates and activates BnaA06.MPK3 and BnaC03.MPK3. The activated BnMPK3 acts on the substrate BnWRKY33 to enhance its transcriptional activity and trigger a transcriptional burst of BnWRKY33, which helps plants effectively resist the pathogenic fungi by enhancing the expression of phytoalexin synthesis-related genes. With constant infection, BnaA03.WRKY28 and BnaA09.VQ12 are induced, and BnaA03.WRKY28 physically interacts with BnaA09.VQ12 to form a protein complex. BnaA03.WRKY28 preferentially binds to the promoter of BnWRKY33 with the help of BnaA09.VQ12. Compared with activated BnWRKY33, BnaA03.WRKY28 has a lower transcriptional activity on downstream BnWRKY33, which leads to weaker resistance against S. sclerotiorum for rapeseed in the later stage of infection. Furthermore, the induced BnaA03.WRKY28 may promote axillary bud activity and axillary meristem initiation by regulating the expression of branching-related genes (such as BnBRC1), thus promoting the formation of branches in the leaf axils. One-sentence summaryUnder constant infection by Sclerotinia sclerotiorum, BnaA03.WRKY28 interacts with BnaA09.VQ12 and takes precedence over phosphorylated BnWRKY33 to bind to the BnWRKY33 promoter, thereby weakening resistance but promoting branching.

plant biology↗

bioRxiv2021

Heterologous vaccination regimens with self-amplifying RNA and Adenoviral COVID vaccines induce superior immune responses than single dose vaccine regimens in mice

Several vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two dose heterologous vaccination regimens than single dose regimens. Neutralising titres after heterologous prime-boost were at least comparable or higher than the titres measured after homologous prime boost vaccination with viral vectors. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+ CD4 T cells which is superior to the response induced in homologous vaccination regimens in mice. These results underpin the need for clinical trials to investigate the immunogenicity of heterologous regimens with alternate vaccine technologies.

immunology↗

bioRxiv2021

Integrated evaluation of telomerase activation and telomere maintenance across cancer cell lines

In cancer, telomere maintenance is critical for the development of replicative immortality. Using genome sequences from the Cancer Cell Line Encyclopedia and Genomics of Drug Sensitivity in Cancer Project, we calculated telomere content across 1,299 cancer cell lines. We find that telomerase reverse transcriptase (TERT) expression correlates with telomere content in lung, central nervous system, and leukemia cell lines. Using CRISPR/Cas9 screening data, we show that lower telomeric content is associated with dependency of CST telomere maintenance components. Increased dependencies of shelterin members are associated with wild-type TP53 status. Investigating the epigenetic regulation of TERT, we find widespread allele-specific expression in promoter-wildtype contexts. TERT promoter-mutant cell lines exhibit hypomethylation at PRC2-repressed regions, suggesting a cooperative global epigenetic state in the reactivation of telomerase. By incorporating telomere content with genomic features across comprehensively characterized cell lines, we provide further insights into the role of telomere regulation in cancer immortality.

cancer biology↗

bioRxiv2020

Recombinant SARS-CoV-2 RBD molecule with a T helper epitope as a built in adjuvant induces strong neutralization antibody response

Without approved vaccines and specific treatment, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading around the world with above 20 million COVID-19 cases and approximately 700 thousand deaths until now. An efficacious and affordable vaccine is urgently needed. The Val308 - Gly548 of Spike protein of SARS-CoV-2 linked with Gln830 - Glu843 of Tetanus toxoid (TT peptide) (designated as S1-4) and without TT peptide (designated as S1-5), and prokaryotic expression, chromatography purification and the rational renaturation of the protein were performed. The antigenicity and immunogenicity of S1-4 protein was evaluated by Western Blotting (WB) in vitro and immune responses in mice, respectively. The protective efficiency of it was measured by virus neutralization test in Vero E6 cells with SARS-CoV-2. S1-4 protein was prepared to high homogeneity and purity by prokaryotic expression and chromatography purification. Adjuvanted with Alum, S1-4 protein stimulated a strong antibody response in immunized mice and caused a major Th2-type cellular immunity compared with S1-5 protein. Furthermore, the immunized sera could protect the Vero E6 cells from SARS-CoV-2 infection with neutralization antibody GMT 256. The candidate subunit vaccine molecule could stimulate strong humoral and Th1 and Th2-type cellular immune response in mice, giving us solid evidence that S1-4 protein could be a promising subunit vaccine candidate.

bioengineering↗

bioRxiv2020

Structure and assembly of the diiron cofactor in the heme-oxygenase-like domain of the N-nitrosourea-producing enzyme SznF

In biosynthesis of the pancreatic cancer drug streptozotocin, the tri-domain nonheme-iron oxygenase, SznF, hydroxylates N{delta} and N{omega} of N{omega}-methyl-L-arginine before oxidatively rearranging the triply modified guanidine to the N-methyl-N-nitrosourea pharmacophore. A previously published structure visualized the mono-iron cofactor in the enzymes C-terminal cupin domain, which effects the final rearrangement, but exhibited disorder and minimal metal occupancy in the site of the proposed diiron cofactor in the N-hydroxylating heme-oxygenase-like (HO-like) central domain. Here we leverage our recent report of an intensely absorbing {micro}-peroxodiiron(III/III) intermediate formed from the Fe2(II/II) complex and O2 to understand assembly of the diiron cofactor in the HO-like domain and to obtain structures with both SznF iron cofactors bound. Tight binding at one diiron subsite is associated with a conformational change, which is followed by weak binding at the second subsite and rapid capture of O2 by the Fe2(II/II) complex. Differences between iron-deficient and iron-replete structures reveal both the conformational change required to form the O2-reactive Fe2(II/II) complex and the structural basis for cofactor instability, showing that a ligand-harboring core helix dynamically refolds during metal acquisition and release. The cofactor also coordinates an unanticipated Glu ligand contributed by an auxiliary helix implicated in substrate binding by docking and molecular dynamics simulation. The additional ligand is conserved in another experimentally validated HO-like N-oxygenase but not in two known HO-like diiron desaturases. Among [~]9600 sequences identified bioinformatically as belonging to the emerging HO-like diiron protein (HDO) superfamily, [~]25% have this carboxylate residue and are thus tentatively assigned as N-oxygenases. Significance statementThe enzyme SznF assembles the N-nitrosourea pharmacophore of the drug streptozotocin. Its central N-oxygenase domain resembles heme-oxygenase (HO) and belongs to an emerging superfamily of HO-like diiron enzymes (HDOs) with unstable metallocofactors that have resisted structural characterization. We investigated assembly of the O2-reactive diiron complex from metal-free SznF and Fe(II) and leveraged this insight to obtain the first structure of a functionally assigned HDO with intact cofactor. Conformational changes accompanying cofactor acquisition explain its instability, and the observation of an unanticipated glutamate ligand that is conserved in only a subset of the HDO sequences provides a potential basis for top-level assignment of enzymatic function. Our results thus provide a roadmap for structural and functional characterization of novel HDOs.

biochemistry↗

bioRxiv2020

Local Gazetteers Reveal Contrasting Patterns of Historical Changes between Apex Predators and Mesopredators in Eastern China

BackgroundHumans have been causing the sixth wave of mass extinction of biodiversity. The situation of predators, especially of carnivores, is a key indicator of biodiversity, and the mesopredator release is a typical phenomenon in ecosystem recess. Local gazetteers are a rich resource for historical biodiversity research. However there are obvious biases in previous studies focusing only on presence records and neglecting the absence records. I recollected and analyzed the records by fixed methods to research historical biodiversity change. MethodsInnovatively, this research used both presence and absence records from local gazetteers to reconstruct the distribution of 8 kinds of mammalian predators (i.e. large carnivores: tigers, leopards, and bears; medium-sized carnivores: wolves, foxes, civets, dholes, and mustelids) in eastern China from 1573C.E.(Common Era) to 1949C.E. (sorted into 4 periods). Then by utilizing statistics methods, e.g. Partial Least Squares Structural Equation Modeling(PLS-SEM), I analyzed the distribution changes(overall and sorted into 5 altitude groups), and the relation between carnivores and the influence from humans. Results & ConclusionsI reconstructed the specific distribution changes of the carnivores and found the changes match the mesopredator release phenomenon. Furthermore, I found the specific relation(e.g. trade-off effect) between carnivores and the influence of humans. Besides, I found that bears and civets may be potential members of the "Tigers - Leopards - Dholes" predator guild. ProspectsI have also collected records for other wild animals from local gazetteers in China. Based on this collection, I have built the Database of Wild Mammal Records in Chinese Local Gazetteers and am building the Database of Wild Bird Records in Chinese Local Gazetteers. I aim to continue relevant studies using these databases in the future.

ecology↗

bioRxiv2020

Hydrazines as versatile chemical biology probes and drug-discovery tools for cofactor-dependent enzymes

Known chemoproteomic probes generally use warheads that tag a single type of amino acid or modified form thereof to identify cases in which its hyper-reactivity underpins function. Much important biochemistry derives from electron-poor enzyme cofactors, transient intermediates and chemically-labile regulatory modifications, but probes for such species are underdeveloped. Here, we have innovated a versatile class of chemoproteomic probes for this less charted hemisphere of the proteome by using hydrazine as the common chemical warhead. Its electron-rich nature allows it to react by both polar and radicaloid mechanisms and to target multiple, pharmacologically important functional classes of enzymes bearing diverse organic and inorganic cofactors. Probe attachment can be blocked by active-site-directed inhibitors, and elaboration of the warhead supports connection of a target to a lead compound. The capacity of substituted hydrazines to profile, discover and inhibit diverse cofactor-dependent enzymes enables cell and tissue imaging and makes this platform useful for enzyme and drug discovery. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/154864v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1e1a54forg.highwire.dtl.DTLVardef@12be680org.highwire.dtl.DTLVardef@129e027org.highwire.dtl.DTLVardef@3b2317_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2020

A new method for distinguishing human and mouse cells in situ

The mouse xenograft model is one of the most widely used animal model for biomedicine research. It is vital to distinguish the cells from different species, especially for the spatial distribution information. However, the available strategies of species-specific detection are either inapplicable in situ or of low specificity. Here, we reported a method based on DAPI staining, which offers an effective, convenient way that accurately identifies human and mouse nuclei at single-cell level in situ. This method was proven to be effective in cell co-culture and tumor xenograft tissue section. Microscopic imaging results shows obvious DAPI plaques-like structures in mouse nuclei, but absent in human nuclei. Moreover, we found these structures are co-localized with mouse major satellite DNA, which is located pericentromere in mouse, but absent in human. Our study provides a high-performance method that can be widely used for distinguish human and mouse cell in situ.

cell biology↗

bioRxiv2020

Optimizing imaging conditions for photoconvertible protein mEos3.2 in live and fixed cells

Photoconvertible fluorescent proteins (PCFPs) are widely used in super-resolution microscopy and studies of cellular dynamics. However, our understanding of their photophysics is still limited, hampering their quantitative application. For example, we do not know the optimal sample preparation methods or imaging conditions to count protein molecules fused to PCFPs by single-molecule localization microscopy in live and fixed cells. We also do not know how the behavior of PCFPs in live cells compares with fixed cells. Therefore, we investigated how formaldehyde fixation influences the photophysical properties of the popular green-to-red PCFP mEos3.2 in fission yeast cells under a wide range of imaging conditions. We estimated photophysical parameters by fitting a 3-state model of photoconversion and photobleaching to the time course of fluorescence signal per yeast cell expressing mEos3.2. We discovered that formaldehyde fixation makes the fluorescence signal, photoconversion rate and photobleaching rate of mEos3.2 sensitive to the buffer conditions by permeabilizing the yeast cell membrane. Under some imaging conditions, the time-integrated mEos3.2 signal per yeast cell is similar in live cells and fixed cells imaged in buffer at pH 8.5 with 1 mM DTT, indicating that light chemical fixation does not destroy mEos3.2 molecules. We also discovered that some red-state mEos3.2 molecules entered an intermediate dark state that is converted back to the red fluorescent state by 561-nm illumination. Our findings provide a guide to compare quantitatively conditions for imaging and counting of mEos3.2-tagged molecules in yeast cells. Our imaging assay and mathematical model are easy to implement and provide a simple quantitative approach to measure the time-integrated signal and the photoconversion and photobleaching rates of fluorescent proteins in cells. STATEMENT OF SIGNIFICANCEMaking quantitative measurements with single-molecule localization microscopy (SMLM) has been impeded by limited understanding of the photophysics of the fluorophores, which is very sensitive to the sample preparation and imaging conditions. We characterized the photophysics of the green-to-red photoconvertible fluorescent protein mEos3.2, which is widely used in SMLM. We combined quantitative fluorescence microscopy and mathematical modeling to measure the fluorescence signal and rate constants for photoconversion and photobleaching of mEos3.2 in live and fixed cells under a wide range of illumination intensities. Our findings provide a guide to compare conditions for imaging and counting mEos3.2-tagged proteins in cells. The presented approach is generally applicable to characterize other fluorescent proteins or dyes in cells.

biophysics↗

bioRxiv2020

Spatial Regulation of MCAK Promotes Cell Polarization and Focal Adhesion Turnover to Drive Robust Cell Migration

The asymmetric distribution of microtubule (MT) dynamics in migrating cells is important for cell polarization, yet the underlying regulatory mechanisms remain underexplored. Here, we addressed this question by studying the role of the MT depolymerase, MCAK, in the highly persistent migration of RPE-1 cells. MCAK knockdown leads to slowed migration and poor directional movement. Fixed and live cell imaging revealed that MCAK knockdown results in excessive membrane ruffling as well as defects in cell polarization and the maintenance of a major protrusive front. Additionally, loss of MCAK increases the lifetime of focal adhesions by decreasing their disassembly rate. These defects are due in part to the loss of the spatial distribution of MCAK activity, wherein activity is higher in the trailing edge of cells compared to the leading edge. Overexpression of Rac1 has a dominant effect over MCAK activity, placing it downstream or in a parallel pathway to MCAK function in migration. Together, our data support a model that places MCAK at a key nexus of a feedback loop, in which polarized distribution of MCAK activity and subsequent differential regulation of MT dynamics contributes to cell polarity and directional migration.

cell biology↗

bioRxiv2020

Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine induces equivalent preclinical antibody titers and viral neutralization to recovered COVID-19 patients

The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle as a vaccine and demonstrate induction of robust neutralization of a pseudo-virus, proportional to quantity of specific IgG and of higher quantities than recovered COVID-19 patients. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic.

immunology↗

bioRxiv2020

Efficacy of transoral laser surgery versus linear accelerator radiotherapy for the treatment of T1 glottic carcinoma: a meta-analysis of oncologic outcomes

ObjectiveA meta-analysis was conducted to compare oncologic outcomes for patients of T1 glottic carcinoma who were treated with transoral laser surgery (TLS) or linear accelerator radiotherapy (linac RT). MethodsAll related studies published up to September 2019 were acquired by searching Pubmed, EMBASE, and Cochrane, with the index words: glottic, vocal, laryngeal, radiation, radiotherapy, irradiation, laser, surgery, cordectomy, carcinoma and cancer. Relative studies which compared oncologic outcomes between linac RT and TLS were included. Sensitivity analysis were performed to evaluate heterogeneity. ResultsA total of twelve eligible studies were included for the analysis, which contained three prospective studies and nine retrospective studies. Patients who underwent TLS had increased overall survival (OR = 1.40, 95% CI=1.02-1.94, P=0.04) and laryngeal preservation (OR = 5.37, 95% CI = 3.05-9.44, P < 0.00001) versus who underwent linac RT. No statistical difference was observed between TLS group and linac RT group in terms of local control (OR=0.88, 95% CI = 0.62-1.24, P = 0.47), disease-specific survival (OR = 0.61, 95% CI = 0.26-1.43, P = 0.26), and disease-free survival (OR = 1.63, 95% CI = 0.70-3.81, P = 0.14). ConclusionsThe results of this meta-analysis indicate that there were clinical benefits for patients with glottic carcinoma after TLS compared with linac RT with respect to overall survival and laryngeal preservation. However, more multi-center randomized controlled trials would be urgently needed to prove these differences.

cancer biology↗