Morphological, immunohistochemical, and genetic analyses of epithelioid gastrointestinal stromal tumors.

Epithelioid gastrointestinal stromal tumors (GISTs) are rare and may be confused with other tumors with epithelioid morphology. Therefore, herein, we collected 12 epithelioid GIST samples and summarized their morphological and immunohistochemical characteristics. Through genetic testing, we explored the correlation between morphology and gene mutations. The results showed that eight tumors showed focal or diffuse myxoid stromal changes with less cohesively arranged rhabdoid tumor cells; among these, five showed platelet-derived growth factor receptor alpha gene (PDGFRA) mutations. Signet ring cells with sclerosing stroma and receptor tyrosine kinase type III gene (KIT) mutations were present in two cases, which might be a KIT mutation-associated growth pattern in epithelioid GISTs. Succinate dehydrogenase gene (SDH) mutations were detected in three cases. Simultaneously, PDGFRA mutations were detected in two cases, and the Kirsten rat sarcoma viral oncogene homolog gene (KRAS) mutation was detected in another case. SDH-subunit B (SDHB) expression was partially weak and strongly diffuse in two cases with concurrent PDGFRA and SDHD mutations, respectively. The coexistence of PDGFRA and SDHD mutations may have affected SDHB expression. Altogether, we concluded that PDGFRA mutations may play an important role in co-mutant GIST pathogenesis.

[Corrigendum] Epigallocatechin­3­gallate inhibits nicotine­induced migration and invasion by the suppression of angiogenesis and epithelial­mesenchymal transition in non­small cell lung cancer cells.

Subsequently to the publication of the above paper, the authors have drawn to the attention of the Editorial Office that a pair of the data panels showing the results of wound­healing assay experiments (in Fig. 1A) and Transwell invasion assays (in Fig. 1B) on p. 2975 were inadvertently featured incorrectly in this figure. Specifically, in Fig. 1A, the 'nicotine + 25 µM EGCG / 0 h' data panel was erroneously copied across to represent the 'nicotine + 0 µM EGCG / 0 h' image, whereas in Fig. 1B, the representative invasion image for the 'nicotine + 10  µM  EGCG' experiment was also incorrectly placed. The authors were able to re­examine their original data files, and realize how the errors were made during the assembly of this figure. The revised version of Fig. 1, showing the correct data for the 'nicotine + 0 µM EGCG / 0 h' in Fig. 1A and the 'nicotine + 10  µM  EGCG' experiment in Fig. 1B, is shown on the next page. Note that the errors made in assembling this figure did not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and all the authors agree with its publication. They also apologize to the readership for any inconvenience caused. [Oncology Reports 33: 2972­2980, 2015; DOI: 10.3892/or.2015.3889].

Long-Term Outcomes and Prognosis Factors in Patients With Idiopathic Inflammatory Myopathies Based on Myositis-Specific Autoantibodies: A Single Cohort Study.

OBJECTIVE: This study was undertaken to investigate the long-term survival rates and prognostic factors in patients with idiopathic inflammatory myopathies (IIMs) based on myositis-specific antibody (MSA) stratification. METHODS: Exactly 628 patients with an IIM were included. Kaplan-Meier survival curves, univariate, and multivariate Cox regression were used to analyze the outcomes and risk factors. RESULTS: The cumulative 1-, 5-, and 10-year survival rates for IIM patients overall were 91.4%, 82.8%, and 75.6%, respectively. The survival rate in the MSA subset was significantly different (P < 0.001). The 1- and 10-year survival rates in the anti-melanoma differentiation-associated protein 5 (anti-MDA-5)-positive subgroup were 79.5% and 58.5%, respectively, which were the lowest among all subgroups. The 10-year survival rate of anti-signal recognition particle (anti-SRP)-positive patients was the highest (96.4%). Independent risk factors that impacted the long-term prognosis for IIM patients included rapidly progressive interstitial lung disease (RP-ILD), malignancy, and elevated serum ferritin levels (hazard ratio [HR] 17.47, 20.36, and 9.15, respectively, P < 0.01), whereas disease duration was a protective factor (HR 0.27, P = 0.003). Among these subsets, the strongest independent risk factor for death in the anti-MDA-5-positive subgroup was RP-ILD (HR 3.4, P = 0.017). Malignancy was an independent risk factor in the anti-aminoacyl-tRNA synthetase antibody-positive, anti-transcription intermediary factor 1γ-positive, and MSA-negative subgroups (HR 46.69, 6.65, and 4.48, respectively; P < 0.001). RP-ILD was also a risk factor in the prognosis of individuals in the MSA-negative subgroup (HR 72.28, P < 0.001). CONCLUSION: Despite favorable overall survival in patients with IIM, the anti-MDA-5-positive subgroup had the highest mortality rate among all MSA subgroups, highlighting the distinctive prognosis for patients with different MSAs. RP-ILD and malignancy are the most common causes of death in IIM patients.

Plastic surgery for giant metastatic endometrioid adenocarcinoma in the abdominal wall: A case report and review of literature.

BACKGROUND: Endometrial cancer (EC) is a common gynecological malignancy, but metastasis to the abdominal wall is extremely rare. Therefore, an appropriate treatment approach for large metastatic lesions with infection remains a great challenge. CASE SUMMARY: We report the case of a 65-year-old woman who developed abdominal metastasis of endometrioid adenocarcinoma, as defined by International Obstetrics and Gynecology stage II, in which the lesion was complicated by infection. A right hemicolectomy was performed for colon metastasis in relation to her initial gynecological cancer 3 years ago. When admitted to our department, a complete resection of the giant abdominal wall lesion was performed, and a Bard composite mesh was used to reconstruct the abdominal wall. A local flap was used to close the resultant large defect in the external covering of the abdomen. The patient underwent chemotherapy following cytoreductive surgery. Pathology revealed metastasis of EC, and molecular subtyping showed copy number high of TP53 mutation, implying a poor prognosis. CONCLUSION: When EC patients develop giant abdominal wall metastasis, a plastic surgeon should be included before contemplating resection of tumors.

Enhancing conversion of polysulfides via porous carbon nanofiber interlayer with dual-active sites for lithium-sulfur batteries.

Lithium-sulfur (Li-S) batteries are promising candidates for next-generation energy storage. However, the notorious lithium polysulfides (LiPSs) shuttle effect and torpid redox kinetics hinder their practical application. Enhancing phase conversion efficiency and limiting the dissolution of LiPSs are critical for stabilizing Li-S batteries. Herein, sulfiphilic defective TiO2 nanoparticles (D-TiO2) were integrated into the lithiophilic N-doped porous carbon nanofiber membrane (D-TiO2@NPCNF) to construct interlayer for catalyzing the conversion of LiPSs. The D-TiO2@NPCNF provides hierarchical porous structure and large specific surface area, and the formed 3D conductive network accelerates the transport of electrons and ions. The dual-active sites (N and D-TiO2) enhance the interface conversion and chemisorption ability of LiPSs via forming "Li-N and Ti-S" bonds. Due to the structural advantage of the D-TiO2@NPCNF, the Li-S batteries exhibit excellent cycling stability (only 0.049% decay per cycle in 800cycles at 1.0C) and impressive specific capacity (608 mAh g-1 at 3.0C). This work is expected to deepen the comprehension of complex interphase conversion processes of LiPSs and provide novel ideas for the design of new interlayer materials.

ZnO-assisted synthesis of lignin-based ultra-fine microporous carbon nanofibers for supercapacitors.

Reducing the material size could be an effective approach to enhance the electrochemical performance of porous carbons for supercapacitors. In this work, ultra-fine porous carbon nanofibers are prepared by electrospinning using lignin/ polyvinylpyrrolidone as carbon precursor and zinc nitrate hexahydrate (ZNH) as an additive, followed by pre-oxidation, carbonization, and pickling processes. Assisted by the ZnO template, the pyrolytic product of ZNH, abundant micropores are yielded, leading to the formation of microporous carbon nanofibers with specific surface area (SSA) up to 1363 m2 g-1. The average diameter of the lignin-based ultra-fine porous carbon nanofibers (LUPCFs) is effectively controlled from 209 to 83 nm through adjusting the ZNH content. With good flexibility and self-standing nature, the LUPCFs could be directly cut into electrodes for use in supercapacitors. High accessible surface, enriched surface N/O groups, and reduced fiber diameters endow the LUPCFs-based electrodes with an excellent specific capacitance of 289 F g-1. The reduction of fiber diameters remarkably improves the rate performance of the LUPCFs and leads to a low relaxation time constant of 0.37 s. The high specific capacitance of 162 F g-1 is maintained when the current density is increased from 0.1 to 20 A g-1. Besides, the fabricated LUPCFs show exceptional cycling stability in symmetrical supercapacitors, manifesting a promising application prospect in the next generation of supercapacitors.

In vivo efficacy studies of novel quinazoline derivatives as irreversible dual EGFR/HER2 inhibitors, in lung cancer xenografts (NCI-H1975) mice models.

Lung cancer is the most common cancer and leading cause of cancer-related deaths worldwide. The first-generation reversible, ATP-competitive inhibitors gefetinib and elotinib showed good clinical responses in lung adenocarcinoma tumors (NSCLC). But almost all patients developed resistance to these inhibitors over time. Such resistance of EGFR inhibitors was frequently linked to the acquired L858R and T790M point mutations in the kinase domain of EGFR. To overcome these resistance problems, the second and the third generation inhibitors have been discovered. FDA approved afatinib, the second generation irreversible inhibitor and osimitinib, the third generation irreversible EGFR inhibitors for the treatments of NSCLC. We identified new covalent quinazoline inhibitors (E)-N-(4-(3-chloro-4-fluorophenylamino)-7-(2-ethoxyethoxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide (6d) and (E)-N-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)-7-(2-ethoxyethoxy)quinazolin-6-yl)-4-(dimethyl-amino)but-2-enamide (6h) that exhibited potent EGFR kinase inhibitory activities on L858R and T790M mutations. The compound 6 h showed selectivity similar to AZD9291 (osimertinib) in mutated and wild type tumor cell lines. In vitro cell assay 6d and 6h were better than afatinib and osimertinib. In vivo antitumor efficacy studies of these compounds were done in NCI-H1975 mice xenografts.

microRNA-221 restricts human cytomegalovirus replication via promoting type I IFN production by targeting SOCS1/NF-κB pathway.

HCMV is a common pathogen for human with relatively high prevalence, which could be life-threatened in immunodeficient patients and lead to significant birth defects in newborns. In this study, we firstly report that HCMV infection significantly enhances the expression of microRNA-221 (miR-221) in Neural Precursor Cells (NPCs). We found that miR-221 directly targets at the 3'-UTR of suppressor of cytokine signaling 1 (SOCS1) and suppresses SOCS1 expression at the both mRNA and protein levels. MiR-221 overexpression restrained HCMV replication by promoting type I interferon (IFN) and interferon stimulating genes (ISGs) production, whereas reintroduction of SOCS1 abrogated the miR-221-induced effects on HCMV replication. Importantly, miR-221 positively regulated the phosphorylation and activation of NF-κB by suppressing SOCS1. What's more, miR-221 agomir alleviated MCMV-induced tissue injury by promoting type I IFN antiviral activities in vivo. Thus, miR-221 modulates the infection and replication of HCMV as an intrinsic antiviral factor, and could be developed as a treatment target for anti-HCMV treatment.

Clinical characteristics of dermatomyositis patients with isolated anti-Ro-52 antibody associated rapid progressive interstitial lung disease: Data from the largest single Chinese center.

AIM: To describe and expand the phenotype of isolated anti-Ro-52-associated rapid progressive interstitial lung disease (RP-ILD) in Dermatomyositis(DM) in Chinese patients. METHODS: 491 patients with PM/DM-ILD hospitalized in the China-Japan Friendship Hospital from 2000 to 2017 were screened retrospectively. All proven cases of isolated anti-Ro-52-associated RP-ILD were selected for inclusion. The clinical features in this group were recorded. RESULTS: Isolated Ro-52 antibodies existed in 20 PM/DM-ILD patients. Among them 5 patients developed RP-ILD. The 5 patients had typical rashes including Gottron's sign (80%), Helitrope rash (80%) and mechanic's hands (100%), but only few patients (20%) had arthralgia and muscle weakness. All patients had elevated levels of serum ferritin and decreased counts of CD3+ T cells. The estimated high-resolution computed tomography (HRCT) patterns of the five patients showed organizing pneumonia (OP) while RP-ILD patients without Ro-52 antibodies and non-RP-ILD patients with isolated Ro-52 antibodies mainly showed non-specific interstitial pneumonia (NSIP) patterns(P < 0.05). Although one patient died of infection after one month, 80%(4/5) of patients had good response to glucocorticoid treatment and these four patients survived were all alive at the end of follow-up. The survival rate in this group was the highest than those in RP-ILD patients with other myositis specific autoantibodies though the difference had no statistically significance. CONCLUSIONS: A small group of patients with isolated anti-Ro-52 antibody in DM could develop RP-ILD, which mainly presented OP on HRCT. Patients with isolated anti-Ro-52 antibody associated RP-ILD responded well to therapy and had good prognosis in DM.

Overexpression of LINC00261 inhibits non-small cell lung cancer cells progression by interacting with miR-522-3p and suppressing Wnt signaling.

Long noncoding RNA LINC00261 has been experimentally validated to function as a tumor suppressor in several cancers, but its pathological role and functional mechanism in non-small cell lung cancer (NSCLC) are largely unclear. In this study, LINC00261 was delineated in NSCLC to be significantly downregulated in cancer tissues compared with corresponding adjacent normal tissues. Low expression of LINC00261 predicted worse survival for patients with NSCLC. Overexpression of LINC00261 in NSCLC cell lines inhibited cell proliferation and invasion, meanwhile promoted apoptosis. Subcellular fractionation assay showed that LINC00261 existed mainly in the cytoplasm of NSCLC A549 cells and luciferase assay validated its direct interaction with miR-522-3p. Overexpression of miR-522-3p significantly ameliorated suppressive effects of LINC00261 on proliferation and invasion of NSCLC cells. Besides, miR-522-3p was found to be able to directly combine with the 3'-untranslated region of SFRP2, which was generally regarded as a suppressor of Wnt signaling. Further quantitative reverse transcription polymerase chain reaction and Western blot experiments showed that LINC00261 upregulation potentiated the expression of SFRP2 and inhibited Wnt signaling pathway, which could both be reversely modulated by miR-522-3p. Taken together, our study demonstrated that LINC00261 suppressed NSCLC cells progression via sponging miR-522-3p and inhibiting Wnt signaling. These results supported us to better understand the pathogenic mechanism of NSCLC and revealed a potential molecular target for this fatal disease.

Design, synthesis of orally bioavailable novel anaplastic lymphoma kinase (ALK) inhibitor diphenylaminopyrimidine analogs and efficacy study on NCI-H2228 xenografts mice model.

Anaplastic lymphoma kinase (ALK) is an attractive therapeutic target for the treatment of non-small cell lung cancer (NSCLC). Within our ALK drug discovery program, we identified novel deuterated 2,4-diarylamino pyrimidine compounds as potent ALK inhibitors. The compound 11 showed better in vitro activity and in vivo efficacy with good pharmacokinetic profile. In vivo efficacy of compound 11 was better than standard drug ceritinib in NCI-H2228 xenograft mice model.

Discovery of new quinazoline derivatives as irreversible dual EGFR/HER2 inhibitors and their anticancer activities - Part 1.

Overexpression of EGFR and HER2 are observed in many breast, ovarian, colon and prostate cancers. The second and third generation irreversible EGFR/HER2 dual kinase inhibitors became popular after the approval of Afatinib by FDA to overcome the mutation related problem. To find efficacious drug candidates, a series of novel quinazoline derivatives were designed, synthesized and evaluated as dual EGFR/HER2 tyrosine kinase (TK) inhibitors. Selected twenty four compounds were reported here with significant inhibitory activities against EGFR/HER2 tyrosine kinases. Several compounds showed nanomolar IC50 values. In vitro studies of quinazoline derivatives were done on NCI-H1975, HCC827, A431, MDA MB-453 cell lines. The compounds 1a, 1d and 1v were found more potent compared to standard drug afatinib. In vivo efficacy study of 1d on nude mice NCI-H1975 tumour xenograft model was discussed.

Preparation of cellulose acetate derived carbon nanofibers by ZnCl2 activation as a supercapacitor electrode.

Porous carbon nanofibers are fabricated by one-step carbonization and activation of electrospun cellulose acetate (CA) nanofibres. Electrospun CA nanofibers were obtained by the electrospinning of a CA/DMAC/acetone solution, followed by deacetylation in NaOH/ethanol solution. One-step carbonization and activation was achieved by dipping the as-spun fibers in ZnCl2 solution, followed by one-step high temperature treatment. The effects of the concentration of the dipping solution on the microstructure of the CA-based carbon nanofibers (CACNFs), including the morphology, crystal structure, porous structure, specific surface area and surface chemical properties, have been investigated. The coating of ZnCl2 effectively improves the thermal stability of electrospun CA nanofibers and obviously enhances the oxygen-containing surface groups of the CACNFs. The CACNFs have a norrow pore size distribution (0.6-1.2 nm) and a high specific surface area (∼1188 m2 g-1). Electrochemical performances of the CACNFs were evaluated as supercapacitor electrodes in 6 M KOH solution. The CACNFs demonstrate high specific capacitance (202 F g-1 at 0.1 A g-1) and excellent rate capability (61% of the retention from 0.1 to 20 A g-1). After 5000 cycles of the electrode, the capacitance is maintained at 92%, and the coulombic efficiency is close to 100%, showing high electrochemical stability and reversibility. The renewable features and excellent performance make CACNFs quite a promising alternative to efficient supercapacitor electrodes for energy storage applications.

Preparation and Comparative Study of Microporous and Mesoporous Carbon Nanofibers as Supercapacitor Electrodes.

Microporous carbon nanofibers (Mi-CNFs) and mesoporous carbon nanofibers (Me-CNFs) with high surface area were prepared by electrospinning resol resin/PVP/TEOS/F127 ethanol solution, followed by curing, carbonization and pickling process. TEOS was responsible for structural stability and producing micropores, while F127 for forming mesopores. Mi-CNFs showed high specific surface area of 1841 m2 g-1, while Me-CNFs possessed both high specific surface area of 1674 m2 g-1 and mesoporosity of 64%. The electrochemical test revealed that Mi-CNFs had higher capacitance (276 F g-1 at 0.5 A g-1) and Me-CNFs possessed higher capacitance retention (71%, 150 F g-1 at 30 A g-1).

Correction to: identification of multiple cancer-associated myositis-specific autoantibodies in idiopathic inflammatory myopathies: a large longitudinal cohort study.

After publication of the article [1], it has been brought to our attention that the labels in Fig. 2b have been switched and are as a result incorrect. The label for the red line should have the label "non-CAM" and the yellow line "CAM".

The prevalence and clinical significance of anti-PUF60 antibodies in patients with idiopathic inflammatory myopathy.

Autoantibodies against poly-U-binding factor 60 kDa protein (PUF60) have been reported in Caucasian dermatomyositis (DM) patients. However, their clinical significance in idiopathic inflammatory myopathy (IIM) remains to be fully clarified. Our objective was to analyze the prevalence and clinical significance of anti-PUF60 antibodies in a large cohort of Chinese IIM patients. In our study, 388 IIM patients, 301 disease controls, and 167 healthy controls (HCs) were involved. An enzyme-linked immunosorbent assay (ELISA) was developed to detect serum anti-PUF60 levels and was validated using immunoblotting methods. Unpaired Mann-Whitney U test and Spearman correlation analysis were used when appropriate. Anti-PUF60 antibodies were observed in IIM patients at a frequency of 10.6% (41/388). Subgrouping analysis revealed that the prevalence of anti-PUF60 antibodies was 10% in DM, 5.5% in polymyositis (PM), 10% in immune-mediated necrotizing myositis (IMNM), and 26.5% in myositis-overlap syndrome. Anti-PUF60 antibodies were also observed in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS) patients at a positive rate of 17.3, 14.5, and 10.1% respectively. Intriguingly, anti-PUF60 antibodies were frequently observed in clinically amyopathic dermatomyositis (CADM) patients and DM patients without currently known myositis autoantibodies. Furthermore, DM patients with anti-PUF60 antibodies had higher prevalence of skin ulcerations. Moreover, longitudinal investigation in eight DM patients with anti-PUF60 antibodies revealed that the antibodies levels decreased with disease remission. Anti-PUF60 antibodies were nonspecific for myositis, since they could be detected in other rheumatic diseases. Further investigation of anti-PUF60 antibodies may reveal shared pathogenic pathways in systemic autoimmune disorders.

Differential Clinical Associations of Anti-Nuclear Matrix Protein 2 Autoantibodies in Patients With Idiopathic Inflammatory Myopathies.

OBJECTIVE: To investigate the associations between anti-nuclear matrix protein 2 (anti-NXP-2) autoantibody levels and disease activity as well as calcinosis severity in patients with idiopathic inflammatory myopathies (IIMs). METHODS: Serum levels of anti-NXP-2 autoantibodies were determined in 709 patients with IIMs and also serially measured in the patients' sera with an in-house enzyme-linked immunosorbent assay using MORC3 recombinant protein. Patients with anti-NXP-2 autoantibodies were divided into 2 subgroups: those with and those without calcinosis. Associations of anti-NXP-2 autoantibody levels with organ-specific disease activity (using 10-cm visual analog scale [VAS] scores), serum creatine kinase (CK) levels, and calcinosis severity were investigated in cross-sectional and longitudinal analyses. RESULTS: A cross-sectional analysis of 56 IIM patients with anti-NXP-2 autoantibodies (38 without calcinosis and 18 with calcinosis) showed that in patients without calcinosis, the levels of anti-NXP-2 autoantibodies were positively correlated with the physician's global assessment of disease activity and muscle VAS scores and serum CK levels, whereas no such association was found in patients with calcinosis. Results of the longitudinal study revealed strong correlations of anti-NXP-2 antibody levels with the physician's global assessment and constitutional, cutaneous, gastrointestinal, and muscle VAS scores and serum CK levels in patients without calcinosis, but in patients with calcinosis, only a moderate correlation was observed between anti-NXP-2 antibody levels and the physician's global VAS and constitutional VAS scores. Of note, in patients without calcinosis, anti-NXP-2 autoantibodies were found to disappear during periods of clinical remission, but reappeared with disease relapse. No association between anti-NXP-2 antibody levels and the severity of calcinosis was observed. CONCLUSION: These findings indicate that anti-NXP-2 autoantibodies serve as a useful marker for disease activity in patients with IIMs, especially in the absence of calcinosis. The differential associations observed between anti-NXP-2 autoantibody levels and disease activity suggest that there may be a phenotypic difference between patients with and those without calcinosis.

Increased Levels of Soluble Programmed Death Ligand 1 Associate with Malignancy in Patients with Dermatomyositis.

OBJECTIVE: To investigate the levels of soluble programmed death ligand 1 (sPD-L1) and evaluate its association with malignancy in patients with dermatomyositis (DM). METHODS: Levels of sPD-L1 were measured in serum from 88 DM patients without malignancies (sDM), 40 with cancer-related DM (CRDM), and 30 healthy controls (HC) using ELISA. The CRDM subjects were divided into new-onset cancers (nCRDM) and stable cancers (sCRDM). Receiver-operating characteristic (ROC) curve analysis was performed to determine the cutoff sPD-L1 value that distinguished patients with nCRDM from those who were sDM. Serum antitranscriptional intermediary factor 1-γ (TIF1-γ) antibodies were detected using immunoblot, and the diagnostic values for malignancy were compared with sPD-L1 levels in patients with DM. RESULTS: Serum sPD-L1 levels were significantly higher in sDM [median 12.3 ng/ml, interquartile range (IQR) 8.4-16.2] than in HC (median 1.3 ng/ml, IQR 0.4-2.2, p = 0.0001). Extremely high sPD-L1 levels were seen in nCRDM (median 18.5 ng/ml, IQR 13.8-22.4), much higher than those in sCRDM (median 8.5 ng/ml, IQR 6.8-11.8, p = 0.0001). The sPD-L1 levels in 4 patients with nCRDM decreased after curative cancer treatment (p = 0.013). ROC curve analysis revealed that the sPD-L1 value distinguishing nCRDM from sDM was 16.1 ng/ml, with an area under the curve value of 0.72 ± 0.04 (p = 0.0001). The combination of sPD-L1 and anti-TIF1-γ antibodies yielded greater specificity and positive predictive value in diagnosing cancer, reaching values of 95% and 70%, respectively. CONCLUSION: Serum sPD-L1 levels increased significantly in sDM, and markedly high sPD-L1 levels could be a diagnostic indicator for malignancies in patients with DM, especially in those with anti-TIF1-γ antibodies.

Clinical Heterogeneity of Interstitial Lung Disease in Polymyositis and Dermatomyositis Patients With or Without Specific Autoantibodies.

BACKGROUND: The aim of this study was to compare the heterogeneity of interstitial lung disease (ILD) in patients with polymyositis and dermatomyositis (PM/DM) according to serological type. METHODS: A total of 182 patients with PM/DM-ILD were observed retrospectively. Antiaminoacyl-tRNA synthetase (ARS) and antimelanoma differentiation-associated gene5 (MDA5) antibodies were screened using immunoblotting approach. The patients with ILD were divided into 3 groups: MDA5 (with anti-MDA5 antibody), ARS (with anti-ARS antibody) and MSN (without anti-MDA5 or anti-ARS antibody) group. Pulmonary features, treatment responses and prognoses were compared among the groups. RESULTS: A higher percentage of rapidly progressive ILD (RP-ILD) occurrences (55.8% versus 25% versus 16.9%, P < 0.001) was observed in the MDA5 group compared to ARS and MSN groups. The MSN group experienced lower dyspnea (48.2% versus 79% versus 71.4%, P = 0.001) and fever (18.1% versus 39.5% versus 37.5%, P = 0.01) frequencies compared to MDA5 and ARS groups. Response to 6-month treatment among 95 patients showed highest deterioration ratio (70%, P = 0.001) of ILD in the MDA5 group. Additionally, the highest frequency of ILD improvement (60%, P = 0.04) was observed in the ARS group. During the observation period, 24 patients died of respiratory failure. The 5-year survival rates were significantly lower in MDA5 group (50.2%) compared to ARS group (97.7%) or the MSN group (91.4%) (P < 0.001). CONCLUSIONS: MDA5-ILD was associated with severe pulmonary manifestations, poor response to treatment and aggravated prognosis. The ARS-ILD group had favorable treatment response and prognosis. MSN-ILD patients had relatively worse treatment response and prognosis compared to the ARS group, even though they expressed milder pulmonary manifestation.