Overcoming strength-ductility tradeoff with high pressure thermal treatment.

Conventional material processing approaches often achieve strengthening of materials at the cost of reduced ductility. Here, we show that high-pressure and high-temperature (HPHT) treatment can help overcome the strength-ductility trade-off in structural materials. We report an initially strong-yet-brittle eutectic high entropy alloy simultaneously doubling its strength to 1150 MPa and its tensile ductility to 36% after the HPHT treatment. Such strength-ductility synergy is attributed to the HPHT-induced formation of a hierarchically patterned microstructure with coherent interfaces, which promotes multiple deformation mechanisms, including dislocations, stacking faults, microbands and deformation twins, at multiple length scales. More importantly, the HPHT-induced microstructure helps relieve stress concentration at the interfaces, thereby arresting interfacial cracking commonly observed in traditional eutectic high entropy alloys. These findings suggest a new direction of research in employing HPHT techniques to help develop next generation structural materials.

POLE2 promotes osteosarcoma progression by enhancing the stability of CD44.

Osteosarcoma (OS) is the most prevalent primary malignancy of bone in children and adolescents. It is extremely urgent to develop a new therapy for OS. In this study, the GSE14359 chip from the GEO database was used to screen differentially expressed genes in OS. DNA polymerase epsilon 2 (POLE2) was confirmed to overexpress in OS tissues and cell lines by immunohistochemical staining, qPCR and Western blot. Knockdown of POLE2 inhibited the proliferation and migration of OS cells in vitro, as well as the growth of tumors in vivo, while the apoptosis rate was increased. Bioinformatics analysis revealed that CD44 and Rac signaling pathway were the downstream molecule and pathway of POLE2, which were inhibited by knockdown of POLE2. POLE2 reduced the ubiquitination degradation of CD44 by acting on MDM2. Moreover, knockdown of CD44 inhibited the tumor-promoting effects of POLE2 overexpression on OS cells. In conclusion, POLE2 augmented the expression of CD44 via inhibiting MDM2-mediated ubiquitination, and then activated Rac signaling pathway to influence the progression of OS, indicating that POLE2/CD44 might be potential targets for OS treatment.

Corrigendum to "Cellular senescence-driven transcriptional reprogramming of the MAFB/NOTCH3 axis activates the PI3K/AKT pathway and promotes osteosarcoma progression" [Genes & Diseases 11 (2024) 952-963].

[This corrects the article DOI: 10.1016/j.gendis.2023.02.028.].

CRMP5 participates in oocyte meiosis by regulating spastin to correct microtubule-kinetochore misconnection.

Our previous studies have suggested that spastin, which aggregates on spindle microtubules in oocytes, may promote the assembly of mouse oocyte spindles by cutting microtubules. This action may be related to CRMP5, as knocking down CRMP5 results in reduced spindle microtubule density and maturation defects in oocytes. In this study, we found that, after knocking down CRMP5 in oocytes, spastin distribution shifted from the spindle to the spindle poles and errors in microtubule-kinetochore attachment appeared in oocyte spindles. However, CRMP5 did not interact with the other two microtubule-severing proteins, katanin-like-1 (KATNAL1) and fidgetin-like-1 (FIGNL1), which aggregate at the spindle poles. We speculate that, in oocytes, due to the reduction of spastin distribution on chromosomes after knocking down CRMP5, microtubule-kinetochore errors cannot be corrected through severing, resulting in meiotic division abnormalities and maturation defects in oocytes. This finding provides new insights into the regulatory mechanisms of spastin in oocytes and important opportunities for the study of meiotic division mechanisms.

Cellular senescence-driven transcriptional reprogramming of the MAFB/NOTCH3 axis activates the PI3K/AKT pathway and promotes osteosarcoma progression.

Osteosarcoma is the most common primary malignancy of bones and primarily occurs in adolescents and young adults. However, a second smaller peak of osteosarcoma incidence was reported in the elderly aged more than 60. Elderly patients with osteosarcoma exhibit different characteristics compared to young patients, which usually results in a poor prognosis. The mechanism underlying osteosarcoma development in elderly patients is intriguing and of significant value in clinical applications. Senescent cells can accelerate tumor progression by metabolic reprogramming. Recent research has shown that methylmalonic acid (MMA) was significantly up-regulated in the serum of older individuals and played a central role in the development of aggressive characteristics. We found that the significant accumulation of MMA in elderly patients imparted proliferative potential to osteosarcoma cells. The expression of MAFB was excessively up-regulated in osteosarcoma specimens and was further enhanced in response to MMA accumulation as the patient aged. Specifically, we first confirmed a novel molecular mechanism between cellular senescence and cancer, in which the MMA-driven transcriptional reprogramming of the MAFB-NOTCH3 axis accelerated osteosarcoma progression via the activation of PI3K-AKT pathways. Moreover, the down-regulation of the MAFB-NOTCH3 axis increased the sensitivity and effect of AKT inhibitors in osteosarcoma through significant inhibition of AKT phosphorylation. In conclusion, we confirmed that MAFB is a novel age-dependent biomarker for osteosarcoma, and targeting the MAFB-NOTCH3 axis in combination with AKT inhibition can serve as a novel therapeutic strategy for elderly patients with osteosarcoma in experimental and clinical trials.

Tumor-induced Osteomalacia: A Case Report and Etiological Analysis with Literature Review.

BACKGROUND: Tumor-induced osteomalacia (TIO) belongs to a rare disease of the paraneoplastic syndrome. Phosphate uric mesenchymal tumor (PMT) is the most common cause of TIO, while the possibility of other tumors cannot be excluded. CASE PRESENTATION: We present a case of a 36-year-old female patient with systemic skeletal abnormalities. The woman complained of low back pain with mild motor dysfunction for 2 years. Laboratory examination showed abnormalities in markers of bone metabolism, parathyroid hormone (PTH), vitamin D and serum phosphorus. Pooled imaging examination indicated extension abnormalities in the skeletal system and a single lesion in the right femoral head. The lesion of the right femoral was imaging with somatostatin receptor-positive, which was highly suggestive of a single neuroendocrine tumor. CT guided right femoral tumorectomy and bone grafting were performed when medical treatment failed. Postoperative pathological diagnosis was phosphate urinary mesenchymal tumor secreting fibroblast growth factor 23 (FGF23), which accorded with pre-operative expectations. The postoperative symptoms were effectively relieved, and indicators returned to normal. CONCLUSION: The tumors causing TIO exhibited significant heterogeneity in terms of tissue origin, pathological characteristics and biological behavior, but the unique common characteristic is the secretion of FGF23. With significant progress in diagnosis and treatment, the clinical follow-up of most TIO patients shows a good prognosis, but the prognosis of those with malignant tumors is relatively poor.

LncRNA MEG3 promotes chemosensitivity of osteosarcoma by regulating antitumor immunity via miR-21-5p/p53 pathway and autophagy.

This study aimed to investigate the role of long non-coding RNA maternally expressed gene 3 (lncRNA MEG3) in chemosensitivity of osteosarcoma (OS), and to reveal the possible underlying mechanisms. In this study, we found that the expression of lncRNA MEG3 was significantly lower in OS tissues and cell lines. Furthermore, lncRNA MEG3 overexpression enhanced chemosensitivity of OS by inhibiting cell proliferation, migration, autophagy, and promoting antitumor immunity. LncRNA MEG3 functioned as miR-21-5 sponge to regulate p53 expression in OS. Mechanically, lncRNA MEG3 promoted OS chemosensitivity by regulating antitumor immunity via miR-21-5p/p53 pathway and autophagy. Collectively, this study provided the evidence that lncRNA MEG3 might be a promising therapeutic target for OS chemoresistance.

Research and Application of Medical Polyetheretherketone as Bone Repair Material.

Polyetheretherketone (PEEK) can potentially be used for bone repair because its elastic modulus is similar to that of human natural bone and good biocompatibility and chemical stability. However, its hydrophobicity and biological inertness limit its application in the biomedical field. Inspired by the composition, structure, and function of bone tissue, many strategies are proposed to change the structure and functionality of the PEEK surface. In this review, the applications of PEEK in bone repair and the optimization strategy for PEEK's biological activity are reviewed, which provides a direction for the development of multifunctional bone repair materials in the future.

Animal models of cancer metastasis to the bone.

Cancer metastasis is a major cause of mortality from several tumors, including those of the breast, prostate, and the thyroid gland. Since bone tissue is one of the most common sites of metastasis, the treatment of bone metastases is crucial for the cure of cancer. Hence, disease models must be developed to understand the process of bone metastasis in order to devise therapies for it. Several translational models of different bone metastatic tumors have been developed, including animal models, cell line injection models, bone implant models, and patient-derived xenograft models. However, a compendium on different bone metastatic cancers is currently not available. Here, we have compiled several animal models derived from current experiments on bone metastasis, mostly involving breast and prostate cancer, to improve the development of preclinical models and promote the treatment of bone metastasis.

Clinical efficacy of customized modular prosthesis in the treatment of femoral shaft metastases.

Purpose: To examine clinical outcomes of a specialized modular prosthesis used to fill a bone deficiency following removal of femoral shaft metastases. Methods: Eighteen patients with femoral shaft metastases who underwent en bloc resection and implantation of a personalized modular prosthesis between December 2014 and December 2019 were retrospectively analyzed. Pain, limb function, and quality of life were evaluated using the visual analog scale (VAS), Musculoskeletal Tumor Society (MSTS) scale, International Society of Limb Salvage (ISOLS) scoring system, Karnofsky Performance Status (KPS) scale, and Nottingham Health Profile (NHP) scale. The Kaplan-Meier technique was used to analyze patient survival. Results: The operation duration was 90-150 min (mean, 115 min), and the osteotomy length was 9-16 cm (mean, 11.72 cm). The patients were followed for 12-62 months (mean, 25.28 months). The VAS and NHP ratings were lower at 3, 6, and 12 months after surgery than before surgery, while the MSTS, ISOLS, and KPS scores were higher after surgery than they had been before. These differences were statistically significant (P<0.05). The survival period was between 7 and 62 months (mean, 20.89 months), and the rates of survival at 1-year and 2-year were 72.22% and 27.78%, respectively. Except for two patients with aseptic prosthesis loosening during the follow-up period, there were no problems. Conclusion: En bloc excision and implantation of a personalized modular prosthesis can reduce pain and improve the ability of patients with femoral shaft metastases to perform daily activities, thereby improving their quality of life.

Clinical effect of surgical resection on primary malignant and invasive bone tumours of the proximal fibula.

There is no unified surgical plan for fibular proximal malignant tumours; therefore, the present study retrospectively analysed the medical records of 19 patients with primary malignant and invasive tumours in the proximal fibula and discussed the postoperative oncological results, complications and postoperative functions of limb salvage surgery. According to pathological classification, there were 10 osteosarcoma cases, 3 chondrosarcoma cases, 2 invasive giant cell osteosarcoma tumour cases, 1 epithelioid sarcoma case, 1 leiomyosarcoma case, 1 fibrosarcoma case and 1 lymphoma case. According to the Enneking instalment, IB stage was found in 2 cases, IIA in 2 cases and IIB in 15 cases. A total of 3 patients underwent Malawer I resection, and 16 patients underwent Malawer II resection. The follow-up period was 11-174 months, with an average of 76.58 months. Local recurrence occurred in three patients and distant metastasis in seven patients; 4 patients succumbed and 15 survived. After biceps femoris tendon reconstruction and lateral collateral ligament insertion, 18 patients had good knee stability. The Musculoskeletal Tumour Society scale ranged between 23 and 29 points, with an average of 27.26 points; the Lysholm Knee Score was 65-84 points, with an average of 83 points. After the resection of proximal fibula primary and invasive tumours, the biceps femoris tendon and lateral collateral ligament insertion point was reconstructed. The data show that this technique can effectively reconstruct stability and restore knee function.

Biomimetic cell membrane-coated nanocarriers for targeted siRNA delivery in cancer therapy.

Small interfering RNA (siRNA) therapeutics for cancer are a focus of increasing research interest. However, the major obstacle to their clinical application is the targeted delivery of siRNA to cancer cells at desirable levels. Cell membrane-coated nanocarriers have the advantage of combining the properties of both cell membranes and nanoparticles (NPs). In this review, we highlight the most common RNAi therapeutics and the extracellular and intracellular barriers to siRNA delivery. Moreover, we discuss clinical applications of different cell membrane-coated nanocarriers for targeted siRNA delivery, including cancer cell membranes (CCMs), platelet membranes, erythrocyte membranes, stem cell membranes, exosome membranes, and hybrid membranes. Taken together, biomimetic cell membrane-coated nanotechnology is a promising strategy for targeted siRNA delivery for cancer treatment.

Characterizing the tumor microenvironment at the single-cell level reveals a novel immune evasion mechanism in osteosarcoma.

The immune microenvironment extensively participates in tumorigenesis as well as progression in osteosarcoma (OS). However, the landscape and dynamics of immune cells in OS are poorly characterized. By analyzing single-cell RNA sequencing (scRNA-seq) data, which characterize the transcription state at single-cell resolution, we produced an atlas of the immune microenvironment in OS. The results suggested that a cluster of regulatory dendritic cells (DCs) might shape the immunosuppressive microenvironment in OS by recruiting regulatory T cells. We also found that major histocompatibility complex class I (MHC-I) molecules were downregulated in cancer cells. The findings indicated a reduction in tumor immunogenicity in OS, which can be a potential mechanism of tumor immune escape. Of note, CD24 was identified as a novel "don't eat me" signal that contributed to the immune evasion of OS cells. Altogether, our findings provide insights into the immune landscape of OS, suggesting that myeloid-targeted immunotherapy could be a promising approach to treat OS.

2-Hydroxy-3-methylanthraquinone inhibits homologous recombination repair in osteosarcoma through the MYC-CHK1-RAD51 axis.

BACKGROUND: Osteosarcoma is a malignant bone tumor that usually affects adolescents aged 15-19 y. The DNA damage response (DDR) is significantly enhanced in osteosarcoma, impairing the effect of systemic chemotherapy. Targeting the DDR process was considered a feasible strategy benefitting osteosarcoma patients. However, the clinical application of DDR inhibitors is not impressive because of their side effects. Chinese herbal medicines with high anti-tumor effects and low toxicity in the human body have gradually gained attention. 2-Hydroxy-3-methylanthraquinone (HMA), a Chinese medicine monomer found in the extract of Oldenlandia diffusa, exerts significant inhibitory effects on various tumors. However, its anti-osteosarcoma effects and defined molecular mechanisms have not been reported. METHODS: After HMA treatment, the proliferation and metastasis capacity of osteosarcoma cells was detected by CCK-8, colony formation, transwell assays and Annexin V-fluorescein isothiocyanate/propidium iodide staining. RNA-sequence, plasmid infection, RNA interference, Western blotting and immunofluorescence assay were used to investigate the molecular mechanism and effects of HMA inhibiting osteosarcoma. Rescue assay and CHIP assay was used to further verified the relationship between MYC, CHK1 and RAD51. RESULTS: HMA regulate MYC to inhibit osteosarcoma proliferation and DNA damage repair through PI3K/AKT signaling pathway. The results of RNA-seq, IHC, Western boltting etc. showed relationship between MYC, CHK1 and RAD51. Rescue assay and CHIP assay further verified HMA can impair homologous recombination repair through the MYC-CHK1-RAD51 pathway. CONCLUSION: HMA significantly inhibits osteosarcoma proliferation and homologous recombination repair through the MYC-CHK1-RAD51 pathway, which is mediated by the PI3K-AKT signaling pathway. This study investigated the exact mechanism of the anti-osteosarcoma effect of HMA and provided a potential feasible strategy for the clinical treatment of human osteosarcoma.

Systematic pan-cancer analysis of the nicotinamide n-methyltransferase in human cancer.

In several tumors, Nicotinamide N-Methyltransferase (NNMT) was identified as a bridge between methylation metabolism and tumorigenesis and was associated with a poor prognosis. This research aims is to study the prognostic value of NNMT in cancer, its relationship with DNA methylation, and the immune microenvironment. On the basis of the Cancer Genome Atlas and the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, Cellminer, Gene Expression Profiling Interactive Analysis, Human Protein Atlas and Clinical Proteomic Tumor Analysis Consortium, we used a series of bioinformatics strategies to investigate the potential carcinogenicity of NNMT, including the relationship between NNMT expression and prognosis, tumor mutational burden, microsatellite instability, and sensitivity analysis of anticancer drugs. The GeneMANIA, STRING, and BioGRID databases were examined for protein-protein interactions, and Gene Ontology and the Kyoto Encyclopedia of Genes were used to infer the signal pathway. The results indicated that NNMT was significantly expressed in several tumor tissues compared to the matching non-tumor tissues. Increased NNMT expression was linked to reduced OS, DSS, and DFI. In addition, there was a link between NNMT expression and TMB and MSI in 18 cancer types, and between NNMT expression and DNA methylation in 23 cancer types. Further study of NNMT gene alteration data revealed that deletion was the most prevalent form of NNMT mutation, and that there was a significant negative association between NNMT expression and mismatch repair genes. In addition, there was a strong positive connection between NNMT and immune infiltration in 28 types of tumors, and the immune cells that infiltrated the tumors displayed a characteristic NNMT pattern. According to the enrichment study, cell migration, cell motility, and cell adhesion were highly enriched in biological processes, and NNMT may be associated with the PI3K-Akt signaling pathway. By downregulating gene methylation or impacting the immunological microenvironment widely, NNMT may drive carcinogenesis and cause a poor prognosis. Our research showed that NNMT could be used as a biomarker of tumor immune infiltration and poor prognosis, thus providing a unique strategy for cancer therapy.

Targeted Delivery of PD-L1-Derived Phosphorylation-Mimicking Peptides by Engineered Biomimetic Nanovesicles to Enhance Osteosarcoma Treatment.

Osteosarcoma is a rare malignant bone-originating tumor that usually occurs in young people. Programmed cell death 1 ligand 1 (PD-L1), an immune checkpoint protein, is highly expressed in osteosarcoma tissues. Several recent studies have indicated that the tumor-related role of PD-L1 in tumors, especially non-plasma membrane (NPM)-localized PD-L1, is not limited to immune regulation in osteosarcoma. Here, mass spectrometry analysis is combined with RNA-seq examination to identify the intracellular binding partners of PD-L1 and elucidate the underlying mechanism of its action. It is found that the NPM-localized PD-L1 interacted with Insulin-like growth factor binding protein-3 (IGFBP3) to promote osteosarcoma tumor growth by activating mTOR signaling. This interaction is enforced after phosphoglyceratekinase1 (PGK1)-mediated PD-L1 phosphorylation. Based on these findings, a phosphorylation-mimicking peptide is designed from PD-L1 and it is encapsulated with a Cyclic RGD (cRGD)-modified red blood cell membrane (RBCM) vesicle (Peptide@cRGD-M). The Peptide@cRGD-M precisely delivers the PD-L1-derived phosphorylation-mimicking peptide into osteosarcoma lesions and significantly promotes its therapeutic effect on the tumor. Therefore, this investigation not only highlights the function of NPM-localized PD-L1, but also uses an engineering approach to synthesize a small molecular peptide capable of inhibiting osteosarcoma growth.

Three-dimensional-printed titanium prostheses with bone trabeculae enable mechanical-biological reconstruction after resection of bone tumours.

Reconstruction after resection has always been an urgent problem in the treatment of bone tumours. There are many methods that can be used to reconstruct bone defects; however, there are also many complications, and it is difficult to develop a safe and effective reconstruction plan for the treatment of bone tumours. With the rapid development of digital orthopaedics, three-dimensional printing technology can solve this problem. The three-dimensional printing of personalised prostheses has many advantages. It can be used to print complex structures that are difficult to fabricate using traditional processes and overcome the problems of stress shielding and low biological activity of conventional prostheses. In this study, 12 patients with bone tumours were selected as research subjects, and based on individualised reverse-engineering design technology, a three-dimensional model of each prosthesis was designed and installed using medical image data. Ti6Al4V was used as the raw material to prepare the prostheses, which were used to repair bone defects after surgical resection. The operation time was 266.43 ± 21.08 minutes (range 180-390 minutes), and intraoperative blood loss was 857.26 ± 84.28 mL (range 800-2500 mL). One patient had delayed wound healing after surgery, but all patients survived without local tumour recurrence, and no tumour metastasis was found. No aseptic loosening or structural fracture of the prosthesis, and no non-mechanical prosthesis failure caused by infection, tumour recurrence, or progression was observed. The Musculo-Skeletal Tumour Society (MSTS) score of limb function was 22.53 ± 2.09 (range 16-26), and ten of the 12 patients scored ≥ 20 and were able to function normally. The results showed that three-dimensional printed prostheses with an individualised design can achieve satisfactory short-term clinical efficacy in the reconstruction of large bone defects after bone tumour resection.

[Clinical application of three-dimensional printed osteotomy guide plate and personalized prosthesis in knee-preserving tumor resection].

Objective: To investigate the mid-term effectiveness of three-dimensional (3D) printed osteotomy guide plate and personalized prosthesis in knee-preserving tumor resection. Methods: The clinical data of 12 patients who underwent knee-preserving tumor resection and reconstruction with 3D printed osteotomy guide plate and personalized prosthesis between September 2016 and October 2018 were retrospectively analyzed. There were 7 males and 5 females. The age ranged from 7 to 59 years, with a median of 44.5 years. There were 11 cases of osteosarcoma and 1 case of fibrosarcoma, all of which were Enneking grade ⅡB. The distance from the tumor to the joint surface was 5.5-8.2 cm, with an average of 6.94 cm. Incision healing, tumor recurrence, periprosthetic fracture, and aseptic loosening were observed after operation. The Musculoskeletal Tumor Society (MSTS) scoring system was used to evaluate the function of the patients, and the knee flexion range of motion was measured. Results: The 12 patients were followed up 41-66 months, with an average of 54.5 months. The length of osteotomy ranged from 14 to 26 cm, with an average of 22.08 cm. Except for 2 patients with superficial infection of incision tissue, no deep infection involving the prosthesis occurred, no patient underwent revision surgery because of prosthesis infection. During the follow-up, local recurrence occurred in 2 cases and distant metastasis occurred in 3 cases. The overall disease-free survival rate was 58.3%. Two patients died of lung metastasis, and the overall survival rate was 83.3%. One patient underwent amputation due to local recurrence, and 1 patient underwent total knee arthroplasty due to prosthesis rupture. No aseptic loosening of the prosthesis and periprosthetic fracture occurred during the follow-up, and the overall prosthesis survival rate was 83.3%. At last follow-up, 10 patients obtained satisfactory knee flexion range of motion that ranged from 95° to 125°, with an average of 110°. Two children could not cooperate with early rehabilitation treatment due to pain, and the knee flexion range of motion was not ideal (50°, 75°). All patients achieved acceptable lower limb function with MSTS scores ranged from 26 to 30, with an average of 28. All patients walked without crutches. Conclusion: The treatment of malignant bone tumors around the knee joint with 3D printed osteotomy guide plate and personalized prosthesis can preserve the articular surface, obtain good limb function, reduce the risk of aseptic loosening of prosthesis, and achieve better mid-term effectiveness.

Rare Bone Metastasis of Neuroendocrine Tumors of Unknown Origin: A Case Report and Literature Review.

BACKGROUND: The neuroendocrine tumor (NET) is rare, accounting for about 0.5% of all tumors. NETs have the characteristics of metastasis, especially lymph nodes, liver, spleen, and bone. CASE PRESENTATION: We report a 30-year-old man diagnosed with a NET with bone metastasis and presented with waist and leg pain. The imaging findings of this case showed multiple osteosclerosis and no apparent bone destruction. We collected the patient's previous examinations, including laboratory, imaging, and pathological examination to get a precise diagnosis. Given this case, we carried out symptomatic support treatment to relieve the patients' pain symptoms. CONCLUSION: Bone metastases from NETs of unknown primary site are rare in both clinical and imaging manifestations. The disease is mainly manifested as multiple osteosclerosis, accompanied by muscle soreness and pain. It is recommended to try chemotherapy for this disorder.

Pan-sarcoma characterization of lncRNAs in the crosstalk of EMT and tumour immunity identifies distinct clinical outcomes and potential implications for immunotherapy.

The epithelial-to-mesenchymal transition (EMT) is a reversible process that may interact with tumour immunity through multiple approaches. There is increasing evidence demonstrating the interconnections among EMT-related processes, the tumour microenvironment, and immune activity, as well as its potential influence on the immunotherapy response. Long non-coding RNAs (lncRNAs) are emerging as critical modulators of gene expression. They play fundamental roles in tumour immunity and act as promising biomarkers of immunotherapy response. However, the potential roles of lncRNA in the crosstalk of EMT and tumour immunity are still unclear in sarcoma. We obtained multi-omics profiling of 1440 pan-sarcoma patients from 19 datasets. Through an unsupervised consensus clustering approach, we categorised EMT molecular subtypes. We subsequently identified 26 EMT molecular subtype and tumour immune-related lncRNAs (EILncRNA) across pan-sarcoma types and developed an EILncRNA signature-based weighted scoring model (EILncSig). The EILncSig exhibited favourable performance in predicting the prognosis of sarcoma, and a high-EILncSig was associated with exclusive tumour microenvironment (TME) characteristics with desert-like infiltration of immune cells. Multiple altered pathways, somatically-mutated genes and recurrent CNV regions associated with EILncSig were identified. Notably, the EILncSig was associated with the efficacy of immune checkpoint inhibition (ICI) therapy. Using a computational drug-genomic approach, we identified compounds, such as Irinotecan that may have the potential to convert the EILncSig phenotype. By integrative analysis on multi-omics profiling, our findings provide a comprehensive resource for understanding the functional role of lncRNA-mediated immune regulation in sarcomas, which may advance the understanding of tumour immune response and the development of lncRNA-based immunotherapeutic strategies for sarcoma.