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| 3. |
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| 4. |
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| 5. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 6. |
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| 7. |
- Clark, DW, et al.
(författare)
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Associations of autozygosity with a broad range of human phenotypes
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
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Tidskriftsartikel (refereegranskat)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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| 8. |
- Deng, Min, et al.
(författare)
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Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
- 2013
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 45:6, s. 697-
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
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| 9. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 10. |
- Lu, Meng, et al.
(författare)
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Zoonotic risk assessment among farmed mammals
- 2023
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Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 186:9, s. 2040-2040.e1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Farmed mammals may act as hosts for zoonotic viruses that can cause disease outbreaks in humans. This SnapShot shows which farmed mammals, and to what extent, are of particular risk of harboring and spreading viruses from viral families that are commonly associated with zoonotic disease. It also discusses genome surveillance methods and biosafety measures.
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| 11. |
- Na, Meng, et al.
(författare)
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Higher stand densities can promote soil carbon storage after conversion of temperate mixed natural forests to larch plantations
- 2021
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Ingår i: European Journal of Forest Research. - : Springer Science and Business Media LLC. - 1612-4669 .- 1612-4677. ; 140:2, s. 373-386
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Tidskriftsartikel (refereegranskat)abstract
- Soil carbon (C) reservoirs held in forests play a significant role in the global C cycle. However, harvesting natural forests tend to lead to soil C loss, which can be countered by the establishment of plantations after clear cutting. Therefore, there is a need to determine how forest management can affect soil C sequestration. The management of stand density could provide an effective tool to control soil C sequestration, yet how stand density influences soil C remains an open question. To address this question, we investigated soil C storage in 8-year pure hybrid larch (Larix spp.) plantations with three densities (2000 trees ha−1, 3300 trees ha−1 and 4400 trees ha−1), established following the harvesting of secondary mixed natural forest. We found that soil C storage increased with higher tree density, which mainly correlated with increases of dissolved organic C as well as litter and root C input. In addition, soil respiration decreased with higher tree density during the most productive periods of warm and moist conditions. The reduced SOM decomposition suggested by lowered respiration was also corroborated with reduced levels of plant litter decomposition. The stimulated inputs and reduced exports of C from the forest floor resulted in a 40% higher soil C stock in high- compared to low-density forests within 8 years after plantation, providing effective advice for forest management to promote soil C sequestration in ecosystems.
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| 12. |
- Na, Meng, et al.
(författare)
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Semi-continuous C supply reveals that priming due to N-mining is driven by microbial growth demands in temperate forest plantations
- 2022
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Ingår i: Soil Biology & Biochemistry. - : Elsevier BV. - 0038-0717. ; 173
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Tidskriftsartikel (refereegranskat)abstract
- Nitrogen (N) availability is a powerful controller of soil carbon (C) cycling in temperate forests, affecting plant productivity and microbial activities. Enhanced rhizosphere input from increased plant productivity can stimulate the decomposition of native soil organic matter (SOM), termed the “priming effect”, with an effect size that is affected by N availability. Using soils from N-fertilization field-experiments conducted in larch and mixed forest plantations, we investigated how N availability influenced the priming of soil organic C (SOC) mineralization and soil organic N (SON) mineralization by adding 13C-labelled glucose semi-continuously (every third day) to simulate the semi-continuous delivery of rhizosphere inputs. We found that semi-continuous additions of glucose induced a repeating pattern for the priming of SOC mineralization with an initial decrease followed by an increase. This repeating pattern of SOC mineralization reversely coincided with repeating dynamics in the level of bacterial growth which first increased followed by a decrease. The labile C additions induced a gradually increasing priming of SON mineralization, which was greater than the priming of SOC mineralization (i.e. “selective microbial N-mining”). The priming of SOC mineralization and SON mineralization were both reduced by N fertilization. Increased priming of SON mineralization was related to stimulated bacterial growth and changes in the microbial C use efficiency. These responses suggested that increased microbial demand for N drove the observed N-mining responses. This microbial N-mining could not be explained by increased oxidative enzyme activities, and was instead linked to microbial growth. In the larch forest with high C-quality, the high priming of SOM mineralization were linked to bacterial growth, while in the mixed forest with low C-quality, the high levels of priming of SOM mineralization was linked to fungal growth. We also observed that labile C input initially decoupled the C and N mineralization from SOM. Within 16 days, however, a new equilibrium developed, where both C and N mineralization from SOM were similarly enhanced by labile C input. Overall, our results suggest that semi-continuous rhizosphere inputs can induce a sustained priming of SOM mineralization driven by the microbial demand for N – increasing the release of CO2 – but that N fertilization could reduce the soil C loss, contributing to enhanced soil C sequestration.
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| 14. |
- Pelaz, B, et al.
(författare)
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Diverse Applications of Nanomedicine
- 2017
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Ingår i: ACS nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 11:3, s. 2313-2381
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Tidskriftsartikel (refereegranskat)
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| 15. |
- Qin, Na, et al.
(författare)
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Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma
- 2021
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Ingår i: Frontiers of Medicine. - : Springer-Verlag New York. - 2095-0217 .- 2095-0225. ; 15:2, s. 275-291
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Tidskriftsartikel (refereegranskat)abstract
- Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95,P= 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
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| 16. |
- Song, Dong Yan, et al.
(författare)
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α-Synuclein induces deficiency in clathrin-mediated endocytosis through inhibiting synaptojanin1 expression
- 2023
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Ingår i: Journal of Neurochemistry. - 0022-3042. ; 167:3, s. 461-484
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease (PD) is an age-related chronic neurological disorder, mainly characterized by the pathological feature of α-synuclein (α-syn) aggregation, with the exact disease pathogenesis unclear. During the onset and progression of PD, synaptic dysfunction, including dysregulation of axonal transport, impaired exocytosis, and endocytosis are identified as crucial events of PD pathogenesis. It has been reported that over-expression of α-syn impairs clathrin-mediated endocytosis (CME) in the synapses. However, the underlying mechanisms still needs to be explored. In this study, we investigated the molecular events underlying the synaptic dysfunction caused by over-expression of wild-type human α-syn and its mutant form, involving series of proteins participating in CME. We found that excessive human α-syn causes impaired fission and uncoating of clathrin-coated vesicles during synaptic vesicle recycling, leading to reduced clustering of synaptic vesicles near the active zone and increased size of plasma membrane and number of endocytic intermediates. Furthermore, over-expressed human α-syn induced changes of CME-associated proteins, among which synaptojanin1 (SYNJ1) showed significant reduction in various brain regions. Over-expression of SYNJ1 in primary hippocampal neurons from α-syn transgenic mice recovered the synaptic vesicle density, clustering and endocytosis. Using fluorescence-conjugated transferrin, we demonstrated that SYNJ1 re-boosted the CME activity by restoring the phosphatidylinositol-4,5-bisphosphate homeostasis. Our data suggested that over-expression of α-syn disrupts synaptic function through interfering with vesicle recycling, which could be alleviated by re-availing of SYNJ1. Our study unrevealed a molecular mechanism of the synaptic dysfunction in PD pathogenesis and provided a potential therapeutic target for treating PD.
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| 17. |
- Tang, Fei, et al.
(författare)
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Critical longitudinal ventilation velocity for smoke control in a tunnel induced by two nearby fires of various distances : Experiments and a revisited model
- 2020
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Ingår i: Tunnelling and Underground Space Technology. - : Elsevier BV. - 0886-7798. ; 105
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Tidskriftsartikel (refereegranskat)abstract
- Fire smoke in a tunnel fire is a key factor causing casualties, thus the critical longitudinal ventilation velocity is a key parameter in tunnel fire safety ventilation design. The correlation of critical longitudinal ventilation velocity for smoke control in a tunnel induced by two nearby fires has rarely been studied experimentally and quantified before, despite the fact that this scenario exists in practice. In this paper, the critical longitudinal ventilation velocities for smoke control in the tunnel, induced by two nearby fires were experimentally quantified, involving various separation distances between the two fires of both axi-symmetrical and linear sources of various heat release rates, with a total of 72 test conditions. Results show that the effect of separation distance between the two fires on the critical longitudinal ventilation velocity, decreases with the increase of fire heat release rates. The critical longitudinal ventilation velocities are found to firstly decrease with increasing separation distance between the two fires, and then remain unchanged when the separation distance between two fires beyond a critical value. A new modified model, involving two fires of various separation distances, is proposed. The model is shown to well represent the experimental results.
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| 18. |
- Yuan, Mingyue, et al.
(författare)
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Limiting resources for soil microbial growth in climate change simulation treatments in the Subarctic
- 2024
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Ingår i: Ecology. - 0012-9658. ; 105:1
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Tidskriftsartikel (refereegranskat)abstract
- The microbial use of resources to sustain life and reproduce influences for example, decomposition and plant nutrient provisioning. The study of “limiting factors” has shed light on the interaction between plants and their environment. Here, we investigated whether carbon (C), nitrogen (N), or phosphorus (P) was limiting for soil microorganisms in a subarctic tundra heath, and how changes in resource availability associated with climate change affected this. We studied samples in which changes in resource availability due to climate warming were simulated by the addition of birch litter and/or inorganic N. To these soils, we supplied factorial C (as glucose), N (as NH4NO3), and P (as KH2PO4/K2HPO4) additions (“limiting factor assays,” LFA), to determine the limiting factors. The combination of C and P induced large growth responses in all soils and, combined with a systematic tendency for growth increases by C, this suggested that total microbial growth was primarily limited by C and secondarily by P. The C limitation was alleviated by the field litter treatment and strengthened by N fertilization. The microbial growth response to the LFA-C and LFA-P addition was strongest in the field-treatment that combined litter and N addition. We also found that bacteria were closer to P limitation than fungi. Our results suggest that, under a climate change scenario, increased C availability resulting from Arctic greening, treeline advance, and shrubification will reduce the microbial C limitation, while increased N availability resulting from warming will intensify the microbial C limitation. Our results also suggest that the synchronous increase of both C and N availability might lead to a progressive P limitation of microbial growth, primarily driven by bacteria being closer to P limitation. These shifts in microbial resource limitation might lead to a microbial targeting of the limiting element from organic matter, and also trigger competition for nutrients between plants and microorganisms, thus modulating the productivity of the ecosystem.
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| 19. |
- Yuan, Mingyue, et al.
(författare)
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Will a legacy of enhanced resource availability accelerate the soil microbial response to future climate change?
- 2022
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Ingår i: Soil Biology and Biochemistry. - : Elsevier BV. - 0038-0717. ; 165
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Tidskriftsartikel (refereegranskat)abstract
- Soil microorganisms play an integral role in the regulation of carbon (C) cycling. In high-latitude ecosystems, climate warming is leading to higher plant productivity, shrub expansion and faster nutrient cycling; all of which increase resource availability to soil microorganisms. To understand how a legacy of enhanced resource availability affects the functional traits of microbial communities, and their feedbacks to further environment change, we collected soils from a field-experiment in a subarctic dry heath, where the consequences of climate warming were simulated by adding birch litter or inorganic N as either chronic additions during three years or as a single extreme addition. Soils were then re-exposed to the same resource or a modified resource environment in the laboratory and were monitored for 2 months. We hypothesized that a history of resource input would affect microbial functional profiles, which could result in two possibilities: 1) soil microbes exposed to a historical resource input would perform better when presented with the same resource, because the communities would be specialized to use the added resource, or 2) soil microbes would perform better when presented with a new resource, because the added resource would relieve the nutrient limitation induced by the previous resource input. We also hypothesized that with the same resource, a chronic and long-term input (i.e., a press disturbance) would select for K-strategists (i.e., fungi), while a sudden and large input (i.e., a pulse disturbance) would select for r-strategists (i.e., bacteria). We observed that bacteria in soils exposed to a history of N input showed a stronger growth response to new litter addition, while fungi in soils with a history of litter input showed a stronger growth response to both new litter and new N additions. When presented with new litter, the increase of fungal growth in soil from the extreme litter field-treatment was lower than in the chronic litter field-treatment, demonstrating that a pulse disturbance could weaken the stimulation of fungal growth. When presented with new litter, the increases of bacterial growth did not differ between the chronic N field-treatment and the extreme N field-treatment, suggesting that bacterial responses were not favoured by a press disturbance. We conclude that the enhanced resource availabilities expected in warming arctic soils will generate a positive microbial feedback to climate change.
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| 20. |
- Zhang, Songhong, et al.
(författare)
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Hydrophobic cryogels prepared via cryo-polymerization as oil carriers for biosynthesis of sophorolipids
- 2020
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Ingår i: Biochemical Engineering Journal. - : Elsevier BV. - 1369-703X. ; 161
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Tidskriftsartikel (refereegranskat)abstract
- Microbial synthesis of high-value biochemicals like biosurfactants using renewable substrates has attracted an intensive interest in the past decade. In this work, the bioproduction of sophorolipids was achieved by fermentation of different vegetable oils with the strain of Candida bombicola A0803 using novel hydrophobic poly(butyl methacrylate)(pBMA) cryogels as the oil substrate delivery carriers. The hydrophobic cryogels were prepared successfully via the cryo-polymerization of the reactive emulsion containing hydrophobic monomers under freezing conditions, and the characterization of cryogels was investigated experimentally. The results showed that the polymerization yields of 70 %–89 % were achieved and the cryogels had supermacropores with the maximum porosities of 92 %–96 % and good elasticity in organic solvents but rigid in water, which could provide preferable release properties for vegetable oils. Theie Young's elasticity modulus varied from 0.096 to 0.951 kPa in ethanol and acetone and the related aqueous solutions. With the pBMA cryogels as the delivery carriers of oil substrates, the maximum concentrations of sophorolipids produced for rapeseed, perilla seed and linseed oils were improved 14.5 %, 54.5 % and 53.7 %, while the maximum productivities were improved 14.5 %, 72.1 % and 42.7 % compared with those under the same fermentation condition of free carriers after 204 h–252 h of cultivation, indicating that the hydrophobic cryogels could be an interesting material for the potential applications in biosynthesis areas.
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| 21. |
- Zhao, Xiaoyu, et al.
(författare)
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Identification of genetically predicted DNA methylation markers associated with non–small cell lung cancer risk among 34,964 cases and 448,579 controls
- 2024
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Ingår i: Cancer. - : John Wiley & Sons. - 0008-543X .- 1097-0142. ; 130:6, s. 913-926
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although the associations between genetic variations and lung cancer risk have been explored, the epigenetic consequences of DNA methylation in lung cancer development are largely unknown. Here, the genetically predicted DNA methylation markers associated with non–small cell lung cancer (NSCLC) risk by a two-stage case-control design were investigated.Methods: The genetic prediction models for methylation levels based on genetic and methylation data of 1595 subjects from the Framingham Heart Study were established. The prediction models were applied to a fixed-effect meta-analysis of screening data sets with 27,120 NSCLC cases and 27,355 controls to identify the methylation markers, which were then replicated in independent data sets with 7844 lung cancer cases and 421,224 controls. Also performed was a multi-omics functional annotation for the identified CpGs by integrating genomics, epigenomics, and transcriptomics and investigation of the potential regulation pathways.Results: Of the 29,894 CpG sites passing the quality control, 39 CpGs associated with NSCLC risk (Bonferroni-corrected p ≤ 1.67 × 10−6) were originally identified. Of these, 16 CpGs remained significant in the validation stage (Bonferroni-corrected p ≤ 1.28 × 10−3), including four novel CpGs. Multi-omics functional annotation showed nine of 16 CpGs were potentially functional biomarkers for NSCLC risk. Thirty-five genes within a 1-Mb window of 12 CpGs that might be involved in regulatory pathways of NSCLC risk were identified.Conclusions: Sixteen promising DNA methylation markers associated with NSCLC were identified. Changes of the methylation level at these CpGs might influence the development of NSCLC by regulating the expression of genes nearby.Plain Language Summary: The epigenetic consequences of DNA methylation in lung cancer development are still largely unknown. This study used summary data of large-scale genome-wide association studies to investigate the associations between genetically predicted levels of methylation biomarkers and non–small cell lung cancer risk at the first time. This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins. These findings will provide a unique insight into the epigenetic susceptibility mechanisms of lung cancer.
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| 22. |
- Zhao, Xue-Ke, et al.
(författare)
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Focal amplifications are associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, we identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, and find focal amplifications in the GCA cohort are associated with the chromothripsis process and may be induced by accumulated DNA damage due to local dietary habits. We observe diverse correlations between the presence of oncogene focal amplifications and prognosis, where ERBB2 focal amplifications positively correlate with prognosis and EGFR focal amplifications negatively correlate with prognosis. Large-scale ERBB2 immunohistochemistry results from 1668 GCA patients show survival probability of ERBB2 positive patients is lower than that of ERBB2 negative patients when their surviving time is under 2 years, however, the tendency is opposite when their surviving time is longer than 2 years. Our observations indicate that the ERBB2 focal amplifications may represent a good prognostic marker in GCA patients.
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