Pay Attention to the Osteochondromas in Fibrodysplasia Ossificans Progressiva.

BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is an extremely rare disease characterized by malformation of the bilateral great toes and progressive heterotopic ossification. The clinical features of FOP occur due to dysfunction of the bone morphogenetic protein (BMP) signaling pathway induced by the mutant activin A type I receptor/activin-like kinase-2 (ACVR1/ALK2) which contributes to the clinical features in FOP. Dysregulation of the BMP signaling pathway causes the development of osteochondroma. Poor awareness of the association between FOP and osteochondromas always results in misdiagnosis and unnecessary invasive operation. CASE PRESENTATION: In this study, we present a case of classical FOP involving osteochondroma. An 18-year-old male adolescent, born with deformity of bilateral big toes, complained multiple masses on his back for 1 year. The mass initially emerged with a tough texture and did not cause pain. It was misdiagnosed as an osteochondroma. After two surgeries, the masses became hard and spread around the entire back region. Meanwhile, extensive heterotopic ossification was observed around the back, neck, hip, knee, ribs, and mandible during follow-up. Osteochondromas were observed around the bilateral knees. No abnormalities were observed in the laboratory blood test results. Whole exome sequencing revealed missense mutation of ACVR1/ALK2 (c.617G > A; p.R206H) in the patient and confirmed the diagnosis of FOP. CONCLUSION: In summary, classical FOP always behaves as a bilateral deformity of the big toes, as well as progressive ectopic ossification and osteochondromas in the distal femur and proximal tibia. An understanding of the association between osteochondromas and FOP aids in diagnosis and avoids unnecessary invasive management in patients.

The combination of baseline neutrophil to lymphocyte ratio and dynamic changes during treatment can better predict the survival of osteosarcoma patients.

Background: Osteosarcoma is a primary malignant bone tumor with a high metastatic potential that accounts for a significant proportion of all bone tumors. The prognosis for patients with metastatic or recurrence disease remains poor. The neutrophil-to-lymphocyte ratio (NLR) has become a potential prognostic biomarker for cancer. Recent evidence suggests that the dynamic changes in neutrophil-to-lymphocyte ratio (NLR) during treatment may be more informative in predicting patient prognosis, but the value of dynamic NLR in osteosarcoma has not yet been determined. Methods: This retrospective study retrospectively analyzed the clinical information of 251 osteosarcoma patients diagnosed and treated in West China Hospital of Sichuan University, explored the impact of baseline NLR and changes in NLR during treatment on the prognosis of osteosarcoma patients, and further combined baseline NLR with Delta NLR to build an NLR staging system. Results: The results showed that both baseline NLR and delta NLR had some predictive ability for the prognosis of osteosarcoma patients (P = 6.90e-4, P = 0.022). Patients with high baseline NLR were more likely to have a decrease in delta NLR (P = 1.24e-10). The NLR stage had a better predictive ability than baseline NLR and delta NLR, and was an independent prognostic factor for overall survival in osteosarcoma patients HR: 2.456 (1.625-3.710) (P = 1.97e-05). Conclusion: NLR has value in continuous monitoring, and continuous monitoring of NLR can better predict the survival of osteosarcoma patients compared to baseline NLR.

Polysaccharide extracted from cultivated Sanghuangporous vaninii spores using three-phase partitioning with enzyme/ultrasound pretreatment: Physicochemical characteristics and its biological activity in vitro.

Sanghuangporous vaninii, as a valuable dietary supplement and medicinal ingredient, contains abundant bioactive polysaccharides that have health-promoting effects. In the present study, four polysaccharides (SVSPs-C, SVSPs-E, SVSPs-U, and SVSPs-E/U) were extracted for the first time from S. vaninii spores by three-phase partitioning (TPP), enzyme pretreatment before TPP (E-TPP), ultrasonic pretreatment before TPP (U-TPP), and enzyme pretreatment followed by ultrasonic before TPP (E/U-TPP) methods, respectively. Their physicochemical characteristics and in vitro pharmacological functions were determined and compared. Results showed that four TPP-based extraction methods had remarkable impacts on the extraction yield, chemical properties, monosaccharide compositions, and molecular weights (Mw) of SVSPs. Specifically, SVSPs-E/U obtained by E/U-TPP showed the highest extraction yield (25.40 %), carbohydrate content (88.50 %), and the lowest protein content (0.86 %). The four SVSPs had high-Mw (183.8-329.1 kDa) and low-Mw (23.0-156.4 kDa) fractions and mainly consisted of galactose, glucose, and mannose with different contents. In vitro bioactivities assays indicated that SVSPs-E/U possessed stronger antioxidant, hypoglycemic, hypouricemic, immunostimulatory, and antitumor activities than those of SVSPs-C, SVSPs-E, and SVSPs-U. Therefore, our results provide an efficient and promising extraction technique for bioactive polysaccharides from S. vaninii spores, as well as SVSPs had the potential to be applied in functional food, pharmaceutical, and cosmetics fields.

Surgical Treatment of Osteosarcoma Induced Distant Pre-Metastatic Niche in Lung to Facilitate the Colonization of Circulating Tumor Cells.

Recently, the major challenge in treating osteosarcoma patients is the metastatic disease, most commonly in the lungs. However, the underlying mechanism of recurrence and metastasis of osteosarcoma after surgical resection of primary tumor remains unclear. This study aims to investigate whether the pulmonary metastases characteristic of osteosarcoma is associated with surgical treatment and whether surgery contributes to the formation of pre-metastatic niche in the distant lung tissue. In the current study, the authors observe the presence of circulating tumor cells in patients undergoing surgical resection of osteosarcoma which is correlated to tumor recurrence. The pulmonary infiltrations of neutrophils and Gr-1+ myeloid cells are characterized to form a pre-metastatic niche upon the exposure of circulating tumor cells after surgical resection. It is found that mitochondrial damage-associated molecular patterns released from surgical resection contribute to the formation of pre-metastatic niche in lung through IL-1ß secretion. This study reveals that surgical management for osteosarcoma, irrespective of the primary tumor, might promote the formation of postoperative pre-metastatic niche in lung which is with important implications for developing rational therapies during peri-operative period.

Three-dimensional printed customized uncemented unipolar prosthesis combined with ligament reconstruction for tumorous defect of the distal femur in children.

BACKGROUND: Hemiarthroplasty following tumor resection of the distal femur in children provides a chance to preserve the proximal tibial physis for limb elongation. Based on three-dimensional (3D) printing technology, the uncemented unipolar prosthesis with joint stability reinforced structures (JSRSs) was custom-designed for our cases. This study aimed to describe the design and assess the short-term outcomes of this refined prosthetic hemiarthroplasty. METHODS: Seven patients (four females and three males) received 3D-printed customized uncemented unipolar prosthesis for hemiarthroplasty after removal of the distal femur, from September 2019 to October 2020 at our Orthopedics department. The limb function, growth of the preserved proximal tibial physis, joint stability, and limb length discrepancy (LLD) were assessed. Complications were recorded. RESULTS: Six patients survived with no evidence of metastasis or local recurrence at the last follow-up, and one patient died of lung metastasis at 19 months postoperatively. Follow-up ranged from 19 to 32 months, with an average of 26 months. Elongation of the tibia was observed in all cases. At the last follow-up, four patients exhibited equal growth length compared with the healthy contralateral tibia. LLD ranged from 0.8 to 1.6 cm with a mean of 1.3 cm. The average knee range of motion was 95.3° of flexion and 4.5° of extension. All patients achieved satisfactory postoperative limb function with a mean MSTS score of 25.8. The results of the drawer, Lachman, and pivot shift tests were negative in all patients. During follow-up, painless joint space narrowing was observed in two patients. The screw for ligament fixation loosened in one of the seven patients at 17 months postoperatively. No subluxation of the joint, angular deformity, or breakage of the implant was detected in the remaining patients. CONCLUSIONS: 3D-printed customized uncemented unipolar prosthesis with JSRS would be a good choice for reconstructing tumorous defect in the distal femur in children.

Recent advances in the bioactive polysaccharides and other key components from Phellinus spp. and their pharmacological effects: A review.

Phellinus spp. is one of the largest genera of Hymenochaetaceae with approximately 220 species, such as P. vaninii, P. buamii, P. linteus, and P. igniarius, these species are considered as precious food supplements and medicinal ingredients in China, Korea, Japan, and other Asian countries for over 2000 years. Phellinus spp. contains abundant bioactive polysaccharides and other key components (e.g., phenolics, terpenes, steroids, etc.). Pharmacological investigations have confirmed that bioactive polysaccharides and other important secondary metabolites from Phellinus spp. possess multiple health-promoting benefits, including antitumor, immunomodulatory, anti-inflammatory, antidiabetic, antioxidant, and antimicrobial effects. However, comprehensive evaluations on the preparation and structural characteristics, bioactivities, and toxicology of these functional components (e.g., polysaccharides, phenolics, terpenes, steroids) from various Phellinus spp. species are very limited, which may restrict the practical application of Phellinus spp. This review summarizes the physicochemical characteristics, pharmacological activities, and possible mechanisms of bioactive components from Phellinus spp. according to published studies from 2017 to 2022. It also surveyed the toxicological assessment for safety and applications of different Phellinus spp. species. This review aims to provide useful references and promising directions for the comprehensive development and utilization of Phellinus spp. in functional foods, pharmaceuticals, and cosmetics.

Prognostic significance of modified lung immune prognostic index in osteosarcoma patients.

Purpose: Osteosarcoma is the most common primary malignancy of bone with a dismal prognosis for patients with pulmonary metastases. Evaluation of osteosarcoma prognosis would facilitate the prognosis consultation as well as the development of personalized treatment decisions. However, there is limited effective prognostic predictor at present. Lung Immune Prognostic Index (LIPI) is a novel prognostic factor in pulmonary cancers, whereas, the prognostic significance of LIPI in osteosarcoma has not yet been well clarified. In this study, we firstly explore the prognostic role of LIPI and further modify this predictive model in osteosarcoma. Patients and methods: A retrospectively study was conducted at Musculoskeletal Tumor Center of West China Hospital between January 2016 and January 2021. Hematological factors and clinical features of osteosarcoma patients were collected and analyzed. The area under curve (AUC) and optimal cuff-off of each single hematological factor was calculated. Results: In this study, lactate dehydrogenase (LDH), derived neurtrophil to lymphocyte ratio (dNLR), and Hydroxybutyrate dehydrogenase (HBDH) have higher AUC values. LIPI was composed of LDH and dNLR and was further modified by combing the HBDH, forming the osteosarcoma immune prognostic index (OIPI). OIPI divided 223 osteosarcoma patients divided into four groups, none, light, moderate, and severe (p < 0.0001). OIPI has a higher AUC value than LIPI and other hematological indexes in t-ROC curve. According to the univariate and multivariate analysis, pathological fracture, metastasis, NLR, platelet-lymphocyte ratio (PLR), and OIPI were associated with the prognosis; and metastasis and OIPI were independent prognostic factors of osteosarcoma patients. An OIPI-based nomogram was also established and could predict the 3-year and 5-year overall survival. In addition, OIPI was also revealed correlated with metastasis and pathological fracture in osteosarcoma. Conclusion: This study first explore the prognostic significance of LIPI in osteosarcoma patients. In addition, we developed a modified LIPI, the OIPI, for osteosarcoma patients. Both the LIPI and OIPI could predict the overall survival of osteosarcoma patients well, while OIPI may be more suitable for osteosarcoma patients. In particular, OIPI may have the ability to identify some high-risk patients from clinically low-risk patients.

Hip reconstruction using a customized intercalary prosthesis with the rhino horn-designed uncemented stem for ultrashort proximal femur segments following tumor resection: a combined biomechanical and clinical study.

BACKGROUND: Hip-preserved reconstruction for patients with ultrashort proximal femur segments following extensive femoral diaphyseal tumor resection is a formidable undertaking. A customized intercalary prosthesis with a rhino horn-designed uncemented stem was developed for the reconstruction of these extensive skeletal defects. METHODS: This study was designed to analyze and compare the differences in the biomechanical behavior between the normal femur and the femur with diaphyseal defects reconstructed by an intercalary prosthesis with different stems. The biomechanical behavior under physiological loading conditions is analyzed using the healthy femur as the reference. Five three-dimensional finite element models (healthy, customized intercalary prosthesis with four different stems implemented, respectively) were developed, together with a clinical follow-up of 12 patients who underwent intercalary femoral replacement. RESULTS: The biomechanical results showed that normal-like stress and displacement distribution patterns were observed in the remaining proximal femur segments after reconstructions with the rhino horn-designed uncemented stems, compared with the straight stem. Stem A showed better biomechanical performance, whereas the fixation system with Stem B was relatively unstable. The clinical results were consistent with the FEA results. After a mean follow-up period of 32.33 ± 9.12 months, osteointegration and satisfactory clinical outcomes were observed in all patients. Aseptic loosening (asymptomatic) occurred in one patient reconstructed by Stem B; there were no other postoperative complications in the remaining 11 patients. CONCLUSION: The rhino horn-designed uncemented stem is outstanding in precise shape matching and osseointegration. This novel prosthesis design may be beneficial in decreasing the risk of mechanical failure and aseptic loosening, especially when Stem A is used. Therefore, the customized intercalary prosthesis with this rhino horn-designed uncemented stem might be a reasonable alternative for the reconstruction of SSPF following extensive tumor resection.

Osteosarcoma immune prognostic index can indicate the nature of indeterminate pulmonary nodules and predict the metachronous metastasis in osteosarcoma patients.

Purpose: The relationship between indeterminate pulmonary nodules (IPNs) and metastasis is difficult to determine. We expect to explore a predictive model that can assist in indicating the nature of IPNs, as well as predicting the probability of metachronous metastasis in osteosarcoma patients. Patients and methods: We conducted a retrospective study including 184 osteosarcoma patients at West China Hospital from January 2016 to January 2021. Hematological markers and clinical features of osteosarcoma patients were collected and analyzed. Results: In this study, we constructed an osteosarcoma immune prognostic index (OIPI) based on the lung immune prognostic index (LIPI). Compared to other hematological markers and clinical features, OIPI had a better ability to predict metastasis. OIPI divided 184 patients into four groups, with the no-OIPI group (34 patients), the light-OIPI group (35 patients), the moderate-OIPI group (75 patients), and the severe-OIPI group (40 patients) (P < 0.0001). Subgroup analysis showed that the OIPI could have a stable predictive effect in both the no-nodule group and the IPN group. Spearman's rank correlation test and Kruskal-Wallis test demonstrated that the OIPI was related to metastatic site and metastatic time, respectively. In addition, patients with IPNs in high-OIPI (moderate and severe) groups were more likely to develop metastasis than those in low-OIPI (none and light) groups. Furthermore, the combination of OIPI with IPNs can more accurately identify patients with metastasis, in which the high-OIPI group had a higher metastasis rate, and the severe-OIPI group tended to develop metastasis earlier than the no-OIPI group. Finally, we constructed an OIPI-based nomogram to predict 3- and 5-year metastasis rates. This nomogram could bring net benefits for more patients according to the decision curve analysis and clinical impact curve. Conclusion: This study is the first to assist chest CT in diagnosing the nature of IPNs in osteosarcoma based on hematological markers. Our findings suggested that the OIPI was superior to other hematological markers and that OIPI can act as an auxiliary tool to determine the malignant transformation tendency of IPNs. The combination of OIPI with IPNs can further improve the metastatic predictive ability in osteosarcoma patients.

Combined and Modified Gibson and Ilioinguinal Approaches in Type II + III Internal Hemipelvectomy for Periacetabular Tumors.

Background: The routine iliofemoral approach and its modifications in type II+III resection require extensive skin incision and massive periacetabular muscle detachment, leading to prolonged hospital stay, increased complication incidence, and impaired lower limb function. Under the management of an enhanced recovery after surgery (ERAS) protocol, a combined and modified Gibson and ilioinguinal (MGMII) approach was used to avoid unnecessary soft tissue trauma during tumor resection and therefore advantageous to patients' return to normal life. Methods: Twenty-five patients with type II + III (including type II) periacetabular tumors who underwent reconstruction with 3D printed customized endoprostheses at our center between January 2017 and March 2019 were included in this study. There were 13 cases using MGMII approach and 12 cases using iliofemoral approach. The operation duration and blood loss were assessed by chart review. The surgical margin was evaluated by the histopathological studies. The reconstruction accuracy, the abductor muscle strength, the 1993 version of the Musculoskeletal Tumor Society (MSTS-93), the Harris Hip scores (HHS), and the limp score were evaluated. Complications were recorded after reviewing the patients' records. Results: The operative duration and blood loss in MGMII group were shorter than those in the iliofemoral group, but the postoperative hemoglobin was slightly higher than that in the iliofemoral group. The MGMII group had stronger postoperative hip abductors, better functional restoration, and relatively fewer patients with higher limp scores. No complication was observed in the MGMII group. In the iliofemoral group, three patients encountered wound healing delay, and one patient suffered deep infection. Conclusions: The MGMII approach can better expose the posterior column of the acetabulum, especially the ischial tuberosity, which is beneficial for avoiding tumor rupture during resection. The MGMII approach also helps to preserve residual muscle function, such as the origin of the gluteus medius, while ensuring the extent of resection.

[Application of modified Gibson combined with modified ilioinguinal approach in treatment of Enneking â ¡+ â ¢ pelvic malignant tumors with three-dimensional printed hemipelvic prosthesis replacement].

Objective: To explore the surgical skills of modified Gibson combined with modified ilioinguinal (MGMII) approach in the treatment of Enneking Ⅱ+Ⅲ pelvic malignant tumors in the three-dimensional (3D) printed customized integrated hemipelvic prosthesis, and to evaluate the convenience and accuracy of the surgical approach and the short-term effectiveness. Methods: Between January 2017 and March 2019, 7 patients with Enneking Ⅱ+Ⅲ pelvic malignant tumors were treated with tumor resection and 3D printed hemipelvic prosthesis replacement via MGMII approach. There were 6 males and 1 female. The age ranged from 23 to 68 years, with an average of 43.7 years. There was 1 chondrosarcoma, 1 Ewing's sarcoma, 1 osteosarcoma, 1 malignant Schwannoma, 2 metastatic renal clear cell carcinoma, and 1 metastatic hepatocellular carcinoma. The Enneking stage of 4 cases of primary malignant tumor was stage ⅡB. The disease duration was 6-12 months, with an average of 9.5 months. The preoperative Harris hip score (HHS) was 82.1±1.4 and the Musculoskeletal Tumor Society (MSTS) score was 21.4±1.1. The tumor size by imaging examination was 5.1-9.1 cm, with an average of 6.9 cm. The operation time, intraoperative blood loss, postoperative blood transfusion volume, and postoperative complications were recorded. Postoperative pathological examination confirmed tumor residue according to R classification criteria. The lower limb length, acetabular height, acetabular eccentricity, abduction angle, and anteversion angle were measured and the bone integration was observed by imaging review. Bilateral abductor muscle strengths were measured, and joint function was evaluated by MSTS score and HHS score. Results: All operations were successfully completed. The operation time was 210-360 minutes (mean, 280.0 minutes); the intraoperative blood loss was 1 300-2 500 mL (mean, 1 785.7 mL); the postoperative blood transfusion volume was 0-11 U (mean, 6.1 U). Postoperative pathological examination confirmed R0 resection assisted by osteotomy guide plate. All incisions healed by first intention. All patients were followed up 30-48 months (mean, 41.3 months). At last follow-up, the imaging review showed the good osseointegration in all 7 cases. There was no significant difference in the lower limb length, acetabular height, acetabular eccentricity, abduction angle, and anteversion angle between the affected side and the healthy side ( P>0.05), all of which met the requirements of anatomical reconstruction. At 3 months after operation, the ratios of muscle strength between the affected side and the healthy side was 68.29%±7.41% at 3 months and 89.86%±2.79% at 12 months, showing a significant difference between the two time points ( t=8.242, P=0.000). At last follow-up, the MSTS score and HHS score were 27.3±0.8 and 96.6±1.4, respectively, which significantly improved when compared with those before operation ( P<0.05). None of the patients had assisted walking at last follow-up. There was no recurrence, death, or complications such as deep infection, dislocation of the prosthesis, or fracture of the prosthesis or screw. Conclusion: MGMII approach can expose the posterior column of the acetabulum, especially the ischial tubercle, which is helpful to avoid tumor rupture during tumor resection and preserve the muscle functions such as gluteus medius and iliac muscle while ensuring the resection scope.

A Nutritional Metabolism Related Prognostic Scoring System for Patients With Newly Diagnosed Osteosarcoma.

Osteosarcoma is a primary malignant bone tumor with high metastatic potential. To date, achieving long-term survival of osteosarcoma patients remains a difficult task. Metabolic reprogramming has emerged as a new hallmark of cancer. However, studies on the prognostic value of hematological markers related to nutritional and metabolism in cancer patients are limited and contradictory. In this retrospective study, we extensively collected 16 hematological markers related to nutritional and metabolism in 223 osteosarcoma patients. A nutritional metabolism related prognostic scoring system (NMRS) in patients with osteosarcoma was constructed by least absolute contraction and selection operator (LASSO) cox regression analysis. Compared with individual hematological indicators, NMRS has stronger predictive power (training set: 0.811 vs. 0.362-2.638; validation set: 0.767 vs. 0.333-0.595). It is an independent prognostic factor for the survival of patients with osteosarcoma [HR: 1.957 (1.375-2.786) training set; HR: 3.146 (1.574-6.266) validation set]. NMRS-based nomograms have good and stable predictive power. NMRS facilitates further risk stratification of patients with the same clinical characteristics.

Hematological Prognostic Scoring System Can Predict Overall Survival and Can Indicate Response to Immunotherapy in Patients With Osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumor with a high metastatic potential. Nowadays, there is a lack of new markers to identify prognosis of osteosarcoma patients with response to medical treatment. Recent studies have shown that hematological markers can reflect to some extent the microenvironment of an individual with the potential to predict patient prognosis. However, most of the previous studies have studied the prognostic value of a single hematological index, and it is difficult to comprehensively reflect the tumor microenvironment of patients. Here, we comprehensively collected 16 hematological markers and constructed a hematological prognostic scoring system (HPSS) using LASSO cox regression analysis. HPSS contains many indicators such as immunity, inflammation, coagulation and nutrition. Our results suggest that HPSS is an independent prognostic factor for overall survival in osteosarcoma patients and is an optimal addition to clinical characteristics and well suited to further identify high-risk patients from clinically low-risk patients. HPSS-based nomograms have good predictive ability. Finally, HPSS also has some hints for immunotherapy response in osteosarcoma patients.

Prognostic value of pretreatment anemia in patients with soft tissue sarcoma: A meta-analysis.

BACKGROUND: Anemia is one of the most common manifestations in patients with cancer. Recently, multiple studies have shown a positive correlation between pretreatment anemia and tumor prognosis. Yet, the relationship between pretreatment anemia and the prognosis of soft tissue sarcomas (STS) is unclear. METHODS: We searched the PubMed and EMBASE databases to identify relevant studies. Eligible studies were included according to the inclusion criteria to assess the relationship between pretreatment anemia and the prognosis of patients with STS. Prognostic significance was determined by studying hazard ratios (HR) and 95% confidence intervals (CIs). RESULTS: A total of 12 studies are included. If there is significant heterogeneity, a random-effects model is used. Pooled data indicated that pretreatment anemia is related to poor overall survival (HR = 2.13; 95%CI = 1.52-2.98), disease-specific survival (HR = 1.53; 95%CI = 1.20-1.96), and disease-free survival (HR = 1.55; 95%CI = 1.10-2.17). The results of the subgroup analysis also support this conclusion. CONCLUSION: Our results suggest that pretreatment anemia may be a prognostic biomarker for STS.

Identification of an IRGP Signature to Predict Prognosis and Immunotherapeutic Efficiency in Bladder Cancer.

BACKGROUND: Identify immune-related gene pairs (IRGPs) signature related to the prognosis and immunotherapeutic efficiency for bladder cancer (BLCA) patients. MATERIALS AND METHODS: One RNA-seq dataset (The Cancer Genome Atlas Program) and two microarray datasets (GSE13507 and GSE31684) were included in this study. We defined these cohorts as training set to construct IRGPs and one immunotherapy microarray dataset as validation set. Identifying BLCA subclasses based on IRGPs by consensus clustering. The Lasso penalized Cox proportional hazards regression model was used to construct prognostic signature and potential molecular mechanisms were analyzed. RESULTS: This signature can accurately predict the overall survival of BLCA patients and was verified in the immunotherapy validation set. IRGP-signatures can be used as independent prognostic risk factor in various clinical subgroups. Use the CIBERSORT algorithm to assess the abundance of infiltrating immune cells in each sample, and combine the results of the gene set enrichment analysis of a single sample to explore the differences in the immune microenvironment between IRPG signature groups. According to the results of GSVA, GSEA, and CIBERSORT algorithm, we found that IRGP is strikingly positive correlated with tumor microenvironment (TME) stromal cells infiltration, indicating that the poor prognosis and immunotherapy might be caused partly by enrichment of stromal cells. Finally, the results from the TIDE analysis revealed that IRGP could efficiently predict the response of immunotherapy in BLCA. CONCLUSION: The novel IRGP signature has a significant prognostic value for BLCA patients might facilitate personalized for immunotherapy.

Signature based on metabolic-related gene pairs can predict overall survival of osteosarcoma patients.

BACKGROUND: Osteosarcoma is a tumour of malignant origin in children and adolescents. Recent progression indicates that it is necessary to develop new therapies to improve the patient's prognosis rather than strengthen anti-tumour chemotherapy. Researchers recently realised that cancer is a kind of disease with a metabolic disorder, and metabolic reprogramming is becoming a new cancer hallmark. Hence, our study's primary purpose is to explore the value of genes related to osteosarcoma metabolism. METHODS: From public databases, three osteosarcoma datasets with adequate clinical information were obtained. Besides, the IMvigor dataset through the 'IMvigor' package as a supplement was downloaded, the metabolic-related genes were identified, and these genes were used to construct the metabolic-related gene pairs (MRGP). Based on the prognosis-related MRGP, two molecular subtypes were identified. There are significant differences in the metabolic characteristics between the two molecular subtypes. Subsequently, the MRGP signature is constructed using the least absolute shrinkage and selection operator regression method. Finally, use SubMap analysis to evaluate the response of patients in the MRPG signature group to immunotherapy. RESULTS: The MRGP signature can reliably predict overall survival in patients with osteosarcoma. The MRGP signature is also associated with osteosarcoma patients' metastatic status and can be used for subsequent risk classification of metastatic patients. The immunotherapy is more likely to benefit the patients in the MRGP low-risk group. CONCLUSION: Metabolic-related gene pairs signature can assess the prognosis of patients with osteosarcoma.

Preoperative Predictors of Early Mortality Risk in Isocitrate Dehydrogenase-Wild-Type Glioblastoma Patients Treated with Standard Therapy.

PURPOSE: Early identification of early mortality for glioblastoma (GBM) patients based on laboratory findings at the time of diagnosis could improve the overall survival. The study aimed to explore preoperative factors associated with higher risk of early death (within 1 year after surgery) for isocitrate dehydrogenase (IDH) -wild-type (wt) GBM patients. PATIENTS AND METHODS: We conducted a retrospective analysis of 194 IDH-wt GBM patients who underwent standard treatment. The probability of dying within 1 year after gross total resection (GTR) was defined as the end point "early mortality". Retrospective collection of predictive factors including clinical characteristics and laboratory data at diagnosis. RESULTS: Median follow-up time after GTR was 16 months (3-41 months). Forty-two patients died within 1 year after surgery (1-year mortality rate: 21.6%). All potential predictive factors were assessed on univariate analyses, which revealed the following factors as associated with higher risk of early death: older age (P = 0.013), occurrence of non-seizures symptoms (P = 0.042), special tumor positions (P = 0.046), higher neutrophil-to-lymphocyte ratio (NLR) (P = 0.015), higher red blood cell distribution width (RDW) (P = 0.019), higher lactate dehydrogenase (LDH) (P = 0.005), and higher fibrinogen (FIB) (P = 0.044). In a multivariate analysis, tumor location (P = 0.012), NLR (P = 0.032) and LDH (P = 0.002) were independent predictors of early mortality. The C-index of the nomogram was 0.795. The calibration curve showed good agreement between prediction by nomogram and actual observation. CONCLUSION: Tumor location, preoperative elevated NLR and serum LDH level were independent predictors for 1-year mortality after GTR. We indicate that increased preoperative NLR or LDH may guide patients to review head magnetic resonance imaging (MRI) more frequently and regularly to monitor tumor progression.

A Hematological-Related Prognostic Scoring System for Patients With Newly Diagnosed Glioblastoma.

BACKGROUND: Glioblastoma is the most common primary malignant brain tumor. Recent studies have shown that hematological biomarkers have become a powerful tool for predicting the prognosis of patients with cancer. However, most studies have only investigated the prognostic value of unilateral hematological markers. Therefore, we aimed to establish a comprehensive prognostic scoring system containing hematological markers to improve the prognostic prediction in patients with glioblastoma. PATIENTS AND METHODS: A total of 326 patients with glioblastoma were randomly divided into a training set and external validation set to develop and validate a hematological-related prognostic scoring system (HRPSS). The least absolute shrinkage and selection operator Cox proportional hazards regression analysis was used to determine the optimal covariates that constructed the scoring system. Furthermore, a quantitative survival-predicting nomogram was constructed based on the hematological risk score (HRS) derived from the HRPSS. The results of the nomogram were validated using bootstrap resampling and the external validation set. Finally, we further explored the relationship between the HRS and clinical prognostic factors. RESULTS: The optimal cutoff value for the HRS was 0.839. The patients were successfully classified into different prognostic groups based on their HRSs (P < 0.001). The areas under the curve (AUCs) of the HRS were 0.67, 0.73, and 0.78 at 0.5, 1, and 2 years, respectively. Additionally, the 0.5-, 1-y, and 2-y AUCs of the HRS were 0.51, 0.70, and 0.79, respectively, which validated the robust prognostic performance of the HRS in the external validation set. Based on both univariate and multivariate analyses, the HRS possessed a strong ability to predict overall survival in both the training set and validation set. The nomogram based on the HRS displayed good discrimination with a C-index of 0.81 and good calibration. In the validation cohort, a high C-index value of 0.82 could still be achieved. In all the data, the HRS showed specific correlations with age, first presenting symptoms, isocitrate dehydrogenase mutation status and tumor location, and successfully stratified them into different risk subgroups. CONCLUSIONS: The HRPSS is a powerful tool for accurate prognostic prediction in patients with newly diagnosed glioblastoma.

Construction of immune-related gene pairs signature to predict the overall survival of osteosarcoma patients.

The purpose of this study is to establish the prognosis of osteosarcoma patients based on the characteristics of immune-related gene pairs. We used the lasso Cox regression model to construct and verify the signature consisting of 14 immune-related gene pairs. This signature can accurately predict the overall survival of osteosarcoma patients and is an independent prognostic factor for osteosarcoma patients. For this we constructed a signature-based nomogram. The results of the nomogram show that our signature can bring clinical net benefits. We then assessed the abundance of infiltrating immune cells in each sample, and combine the results of the gene set enrichment analysis of a single sample to explore the differences in the immune microenvironment between IRPG signature groups. The result of gene set enrichment analysis shows the strong relationship between signature and immune system. Finally, we evaluated the relationship between signature and immunotherapy efficiency using algorithms such as TIMI and SubMap to explore patients who might benefit from immunotherapy. In conclusion, our signature can predict the overall survival rate of osteosarcoma patients and provide potential guidance for exploring patients who may benefit from immunotherapy.