Dysregulated serum lipid profile is associated with inflammation and disease activity in primary Sjögren's syndrome: a retrospective study in China.

PURPOSE: To investigate the relationship between the lipid profiles of patients with primary Sjögren's syndrome (pSS) and other clinical characteristics, laboratory examination, disease activity, and inflammatory factors. In addition, the risk factors for hyperlipidemia-related complications of pSS and the effect of hydroxychloroquine (HCQ) usage on the lipid profile were incorporated into this study. METHODS: This is a single-center, retrospective study that included 367 patients who were diagnosed with pSS at Tongji Hospital, School of Medicine, Tongji University, China from January 2010 to March 2022. Initially, demographic information, clinical characteristics, medication records, and complications of the patients were gathered. A case-control analysis compared the 12 systems involvement (ESSDAI domain), clinical symptoms, and laboratory tests between pSS patients with and without dyslipidemia. A simple linear regression model was employed to investigate the relationship between serum lipid profile and inflammatory factors. Logistics regression analysis was performed to assess variables for hyperlipidemia-related complications of pSS. The paired t-test was then used to evaluate the improvement in lipid profile among pSS patients. RESULTS: 48.7 % of all pSS patients had dyslipidemia, and alterations in lipid levels were related to gender, age, and smoking status but not body mass index (BMI). Dyslipidemia is more prevalent in pSS patients who exhibit heightened autoimmunity and elevated levels of inflammation. Higher concentrations of multiple highly inflammatory factors correlate with a more severe form of dyslipidemia. Non-traditional cardiovascular risk factors may contribute to hyperlipidemia-related complications of pSS, such as increased, low complement 3 (C3) and low C4. According to our study, HCQ usage may protect against lipid-related disease in pSS. CONCLUSION: Attention should be paid to the dyslipidemia of pSS. This research aims to clarify the population portrait of pSS patients with abnormal lipid profiles and provides insights into the correlation between metabolism and inflammation in individuals with pSS and the potential role they play in the advancement of the disease. These findings provide novel avenues for further understanding the underlying mechanisms of pSS pathogenesis.

CD146, a therapeutic target involved in cell plasticity.

Since its identification as a marker for advanced melanoma in the 1980s, CD146 has been found to have multiple functions in both physiological and pathological processes, including embryonic development, tissue repair and regeneration, tumor progression, fibrosis disease, and inflammations. Subsequent research has revealed that CD146 is involved in various signaling pathways as a receptor or co-receptor in these processes. This correlation between CD146 and multiple diseases has sparked interest in its potential applications in diagnosis, prognosis, and targeted therapy. To better comprehend the versatile roles of CD146, we have summarized its research history and synthesized findings from numerous reports, proposing that cell plasticity serves as the underlying mechanism through which CD146 contributes to development, regeneration, and various diseases. Targeting CD146 would consequently halt cell state shifting during the onset and progression of these related diseases. Therefore, the development of therapy targeting CD146 holds significant practical value.

Cdc42-driven endosomal cholesterol transport promotes collateral resistance in HER2-positive gastric cancer.

Resistance to trastuzumab and the poor efficacy of subsequent chemotherapy have become major challenges for HER2-positive gastric cancer (GC). As resistance evolves, tumor cells may acquire a new drug susceptibility profile, profoundly impacting the subsequent treatment selection and patient survival. However, the interplay between trastuzumab and other types of drugs in HER2-positive GC remains elusive. In our study, we utilized resistant cell lines and tissue specimens to map the drug susceptibility profile of trastuzumab-resistant GC, discovering that resistance to trastuzumab induces collateral resistance to commonly used chemotherapeutic agents. Additionally, patients with collateral resistance distinguished by a 13-gene scoring model in HER2-positive GC cohorts are predicted to have a poor prognosis and may be sensitive to cholesterol-lowering drugs. Mechanistically, endosomal cholesterol transport is further confirmed to enrich cholesterol in the plasma membrane, contributing to collateral resistance through the Hedgehog-ABCB1 axis. As a driver for cholesterol, Cdc42 is activated by the formation of the NPC1-TßRI-Cdc42 complex to facilitate endosomal cholesterol transport. We demonstrated that inhibiting Cdc42 activation with ZCL278 reduces cholesterol levels in the plasma membrane and reverses collateral resistance between trastuzumab and chemotherapy in vitro and in vivo. Collectively, our findings verify the phenomena and mechanism of collateral resistance between trastuzumab and chemotherapy, and propose a potential therapeutic target and strategy in the second-line treatment for trastuzumab-resistant HER2-positive GC.

Hybrid Organic-Inorganic Additive for Robust Al Anode in Alkaline Aluminum-Air Battery.

Aluminum-air batteries (AABs), known for their high energy density, environmental friendliness, and cost-effectiveness, show immense promise in the realm of energy conversion applications. Nonetheless, their commercialization has encountered inherent challenges of Al anode corrosion and material degradation. In this study, economical hybrid electrolyte additives to inhibit the Al corrosion are developed, safeguarding the integrity of the Al anode. Due to the synergistic interplay between the organic compound dithiothreitol, and inorganic compounds zinc chloride, a robust zinc film is formed on the Al surface This Zn film plays a pivotal role in quelling parasitic hydrogen evolution reactions that typically can plague the Al electrode. Consequently, the as-prepared hybrid additive culminates in a remarkable enhancement to AABs, delivering exceptional discharge capacity of 1793.37 mAh g-1 , high energy density of 2047 Wh kg-1 , and excellent battery longevity (over 20 h in on/off cycling tests). This study, therefore, introduces a novel approach in utilizing hybrid electrolyte additives to effectively counteract corrosion-related challenges and boost the stability and performance of AABs.

CLMP is a tumor suppressor that determines all-trans retinoic acid response in colorectal cancer.

CAR-like membrane protein (CLMP) is a tight junction-associated protein whose mutation is associated with congenital short bowel syndrome (CSBS), but its functions in colorectal cancer (CRC) remain unknown. Here, we demonstrate that CLMP is rarely mutated but significantly decreased in CRC patients, and its deficiency accelerates CRC tumorigenesis, growth, and resistance to all-trans retinoic acid (ATRA). Mechanistically, CLMP recruits ß-catenin to cell membrane, independent of cadherin proteins. CLMP-mediated ß-catenin translocation inactivates Wnt(Wingless and INT-1)/ß-catenin signaling, thereby suppressing CRC tumorigenesis and growth in ApcMin/+, azoxymethane/dextran sodium sulfate (AOM/DSS), and orthotopic CRC mouse models. As a direct target of Wnt/ß-catenin, cytochrome P450 hydroxylase A1 (CYP26A1)-an enzyme that degrades ATRA to a less bioactive retinoid-is upregulated by CLMP deficiency, resulting in ATRA-resistant CRC that can be reversed by administering CYP26A1 inhibitor. Collectively, our data identify the anti-CRC role of CLMP and suggest that CYP26A1 inhibitor enable to boost ATRA's therapeutic efficiency.

Efficacy and safety of robot-assisted laparoscopic myomectomy versus laparoscopic myomectomy: a systematic evaluation and meta-analysis.

OBJECTIVE: Systematic evaluation of the efficacy and safety of robotic-assisted laparoscopic myomectomy (RALM) versus laparoscopic myomectomy (LM). METHODS: PubMed, Embase, The Cochrane Library, and Web of Science database were searched by computer to seek relevant literature in order to compare the efficacy and safety of RALM with that of LM from the establishment of the databases to January 2023, and Review Manager 5.4 software was utilized to perform a meta-analysis on the literature. RESULTS: A total of 15 retrospective clinical controlled studies were included. There exists a total of 45,702 patients, among 11,618 patients in the RALM group and the remaining 34,084 patients in the LM group. Meta-analysis results revealed that RALM was associated with lesser intraoperative bleeding (MD = - 32.03, 95%CI - 57.24 to - 6.83, P = 0.01), lower incidence of blood transfusions (OR = 0.86, 95%CI 0.77 to 0.97, P = 0.01), shorter postoperative hospital stay (MD = - 0.11, 95%CI - 0.21 to - 0.01, P = 0.03), fewer transitions to open stomach (OR = 0.82, 95%CI 0.73 to 0.92, P = 0.0006), and lower incidence of postoperative complications (OR = 0.58, 95%CI 0.40 to 0.86, P = 0.006) than LM, whereas LM is more advantageous in terms of operative time (MD = 38.61, 95%CI 19.36 to 57.86, P < 0.0001). There was no statistical difference between the two surgical methods in terms of maximum myoma diameter (MD = 0.26, 95%CI - 0.17 to 0.70, P = 0.24). CONCLUSION: In the aspects of intraoperative bleeding, lower incidence of blood transfusions, postoperative hospital stay, transit open stomach rate, and postoperative complications, RALM has a unique advantage than that of LM, while LM has advantages over RALM in terms of operative time.

Targeting intratumor heterogeneity suppresses colorectal cancer chemoresistance and metastasis.

Intratumor heterogeneity (ITH) is a barrier to effective therapy. However, it is largely unknown how ITH is established at the onset of tumor progression, such as in colorectal cancer (CRC). Here, we integrate single-cell RNA-seq and functional validation to show that asymmetric division of CRC stem-like cells (CCSC) is critical for early ITH establishment. We find that CCSC-derived xenografts contain seven cell subtypes, including CCSCs, that dynamically change during CRC xenograft progression. Furthermore, three of the subtypes are generated by asymmetric division of CCSCs. They are functionally distinct and appear at the early stage of xenografts. In particular, we identify a chemoresistant and an invasive subtype, and investigate the regulators that control their generation. Finally, we show that targeting the regulators influences cell subtype composition and CRC progression. Our findings demonstrate that asymmetric division of CCSCs contributes to the early establishment of ITH. Targeting asymmetric division may alter ITH and benefit CRC therapy.

Chronic Epstein-Barr virus infection: A potential junction between primary Sjögren's syndrome and lymphoma.

Primary Sjögren's syndrome (pSS) is an autoimmune disease that targets exocrine glands, leading to exocrine dysfunction. Due to its propensity to infect epithelial and B cells, Epstein-Barr virus (EBV) is hypothesized to be related with pSS. Through molecular mimicry, the synthesis of specific antigens, and the release of inflammatory cytokines, EBV contributes to the development of pSS. Lymphoma is the most lethal outcome of EBV infection and the development of pSS. As a population-wide virus, EBV has had a significant role in the development of lymphoma in people with pSS. In the review, we will discuss the possible causes of the disease.

Osteoarthritis or arthritis? Toward understanding of primary Sjögren's syndrome patients with arthralgia.

OBJECTIVE: To identify primary Sjögren's syndrome (pSS) patients with arthralgia at risk for osteoarthritis (OA) or arthritis. METHODS: This study included 368 pSS patients admitted to a mono-centric from March 2010 to December 2020. Patients were divided into groups according to whether complicated with OA or arthritis. Data were analyzed to determine the differences in demographical characteristics, symptoms, and laboratory examination. RESULTS: The involvement of the OA joints was predominately knee and spine sites (including cervical and lumbar spine degeneration). When diagnosing arthritis, it was mainly peripheral symmetric polyarthritis, the most affected sites were the interphalangeal and metacarpophalangeal joints. There were significant differences in age, disease duration, uric acid (UA), and total cholesterol (TC) between pSS-OA and pSS-nOA patients (P < 0.050). Logistic regression analysis showed that age (OR = 1.965; P = 0.009) and joint pain (OR = 3.382; P < 0.001) were dangerous factors associated with OA. Interestingly, although the level of UA, TC, and triglycerides (TG) was shown to be positive with OA, there was no statistical significance after the OR was computed in the four-cell table. In pSS-arthritis, EULAR Sjögren's syndrome disease activity index (ESSDAI) (P = 0.011), the frequency of joint pain (P < 0.001), and muscular involvement (P = 0.037) were higher than non-arthritis group. In pSS patients only presenting with joint pain, arthritis patients had higher ESSDAI and system involvements, but lower UA and TG levels compared with OA group (P < 0.050). CONCLUSION: In pSS patients with arthralgia, OA accounted for the majority. pSS patients with advanced age and more pronounced metabolic characteristics, such as elevated blood lipids and uric acid, was a key factor in groups at risk for OA. However, arthritis patients had higher rates of dry mouth and eye, higher disease activity, antibodies positive, and more organs damage. In the future, it may be necessary to be more cautious in the diagnosis of joint manifestations in pSS patients in order to make the appropriate treatments.

Case report: identification of EGFR R776H and FANCE R381H germline mutations in a patient with multiple pulmonary nodules.

Pulmonary nodules evaluation is clinically crucial because they may be the early predictors of lung cancer. Except for CT screening and serum tumor biomarkers testing, genetic alteration analysis by next-generation sequencing (NGS) technology can also help to find cancer earlier. In this study, we report a case of multiple pulmonary nodules patient with EGFR R776H and FANCE R381H germline mutations. Her father, paternal aunt, and elder uncle harbored either one or both two mutations and were found with multiple pulmonary ground-glass or sub-solid nodules. Her 7-year-old daughter also inherited the same two mutations.

Predictors of poor prognosis in ANCA-associated vasculitis (AAV): a single-center prospective study of inpatients in China.

To identify potential predictors by assessing adverse outcomes in ANCA-associated vasculitis (AAV) patients. Eighty-nine untreated AAV patients were followed up to January 31, 2022, death, or loss of follow-up. Clinical characteristics, laboratory tests, treatment, and progress were collected, and disease activity was evaluated via Birmingham Vasculitis Activity Score (BVAS). We determined risk factors of high-risk events, defined as developing tumors, renal replacement therapy (RRT), and death. Patients and renal survivals were computed by the Kaplan-Meier curve analysis. Cox regression analysis was performed for assessing variables for predicting death. During 267 person-years follow-up, 46 patients occurred high-risk events, including 20 patients receiving RRT, 12 patients developing tumors, and 29 patients who died mostly from organ failure and infection. Decreased estimated glomerular filtration rate (eGFR) (P < 0.001) and complement 3 levels (P = 0.019) were associated with high-risk events. Patients with lower serum potassium tended to develop tumors (P = 0.033); with higher BVAS (HR = 1.290, 95%CI 1.075-1.549, P = 0.006) and lower eGFR (HR = 0.782, 95%CI 0.680-0.901, P = 0.001) were more likely to undergo RRT. Patients with cardio and renal involvement exhibited a lower frequency of renal survival and all-cause mortality. Through multivariate COX analysis, age (HR = 1.016, 95%CI 1.016-1.105, P = 0.006) and eGFR (HR = 0.982, 95%CI 0.968-0.997, P = 0.018) predicted death in AAV, separately. The BVAS and eGFR could be a great prognosticator for RRT, while age and eGFR can independently predict the death. Serum potassium level and immunoglobulins should be focused on their predictor value in development of cancer and renal outcomes in AAV patients.

Predictors of long-term abstinence in a randomized controlled trial of smoking cessation by mobile phone text messaging ('Happy Quit') in China.

INTRODUCTION: The mobile phone-based text messaging intervention ('Happy Quit') is a minimal and effective intervention with very wide reach; thus, it has the possibility of a population impact on quitting rates. Obtaining information on predictors of long-term quit rates is crucial for developing and implementing more effective mobile-based interventions. The study aimed to explore the predictors of long-term abstinence following the 'Happy Quit' intervention. METHODS: This study is a secondary analysis of a randomized controlled trial (RCT) that compared 12-week text messaging intervention ('Happy Quit') versus control intervention with follow-up at 24 weeks, in China. Only participants who had biochemically verified continuous smoking abstinence at 24 weeks were followed up at 52 weeks after the quit date. This predictor regression analysis is for those who were biochemically verified continuous 52-week quitters (n=67) compared with the other participants (n=1302) in the RCT. RESULTS: Of the 69 smokers who were continuously abstinent at 24 weeks, 97.1% (n=67) remained continuously abstinent at 52 weeks. The biochemically verified long-term (52 weeks or 1year) quit rate was 6.3% in the intervention group (60/958), 1.7% in the control group (7/411) (OR=3.677; 95% CI: 1.67-8.11, p<0.001). Multivariable regression analysis revealed that only smoked ≤10 cigarettes per day (compared with >10 cigarettes per day) was the only predictor for long-term abstinence. CONCLUSIONS: This study suggests that individuals who are light smokers might get the most benefit from the text messaging intervention ('Happy Quit') in China.

MCM10 is a Prognostic Biomarker and Correlated With Immune Checkpoints in Ovarian Cancer.

Background: Microchromosome maintenance protein 10 (MCM10) is required for DNA replication in all eukaryotes, and it plays a key role in the development of many types of malignancies. However, we currently still do not know the relationship between MCM10 and ovarian cancer (OV) prognosis and immune checkpoints. Methods: The Gene Expression Profiling Interactive Analysis and Tumor Immunology Estimation Resource (TIMER) databases were used to investigate MCM10 expression in Fan cancer. The Kaplan-Meier Plotter and PrognoScan were used to assess the relationship between MCM10 and OV prognosis. The LinkedOmics database was used to analyze the MCM10 co-expression network and explore GO term annotation and the KEGG pathway. The relationship between MCM10 expression and immune infiltration in OV was investigated using the Tumor Immunology Estimation Resource database. cBioPortal database was used to explore the relationship between MCM10 expression and 25 immune checkpoints. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect MCM10 expression. The prognosis was also analyzed by distinguishing between high and low expression groups based on median expression values. Results: The results of the three data sets (220,651_s_at, 222,962_s_at and 223,570_at) in KM Plotter all indicated that the overall survivalof the high MCM10 expression group was lower than that of the low expression group OV, and the results of GSE9891 also reached the same conclusion. The expression level of MCM10 was negatively correlated with B cells and CD8+T cells, and positively correlated with CD4+T Cells and Macrophages. GO term annotation and KEGG pathway analysis showed that the co-expressed genes of MCM10 were mainly enriched in cell cycle and DNA replication. The alterations in MCM10 coexisted statistically with the immune checkpoints CTLA4, TNFSF4, TNFSF18, CD80, ICOSLG, LILRB1 and CD200. PCR results displayed that MCM10 was highly expressed in OV tissues, and the increased expression of MCM10 was significantly associated with poor overall survival. Conclusion: These results demonstrated that high expression of MCM10 was associated with poor prognosis in OV and correlated with immune checkpoints.

Corrigendum: PET/Ct Imaging of Activated Cancer-Associated Fibroblasts Predict Response to PD-1 Blockade in Gastric Cancer Patients.

[This corrects the article DOI: 10.3389/fonc.2021.802257.].

Relapsing Polychondritis Associated with Miscellaneous Ocular Symptoms and Increased IgA: a Case Report.

A male patient had suffered miscellaneous ocular symptoms for 20 years with auricular dysmorphosis and was diagnosed with Relapsing Polychondritis (RP) in the ear, nose, joints, and costal cartilage. The patient lost his vision owing to recurrent ocular symptoms for decades. He presented an increased IgA and was diagnosed with monoclonal gammopathy of undetermined significance (MGUS) and treated by prednisone and cyclophosphamide. His ocular symptoms relieved and serum IgA decreased after six months. In conclusion, RP is a systemic disease with a wide range of clinical symptoms and may lead to serious complications.

Disrupting Circadian Rhythm via the PER1-HK2 Axis Reverses Trastuzumab Resistance in Gastric Cancer.

Trastuzumab is the only approved targeted drug for first-line treatment of HER2-positive advanced gastric cancer, but the high rate of primary resistance and rapid emergence of secondary resistance limit its clinical benefits. We found that trastuzumab-resistant (TR) gastric cancer cells exhibited high glycolytic activity, which was controlled by hexokinase 2 (HK2)-dependent glycolysis with a circadian pattern [higher at zeitgeber time (ZT) 6, lower at ZT18]. Mechanistically, HK2 circadian oscillation was regulated by a transcriptional complex composed of PPARγ and the core clock gene PER1. In vivo and in vitro experiments demonstrated that silencing PER1 disrupted the circadian rhythm of PER1-HK2 and reversed trastuzumab resistance. Moreover, metformin, which inhibits glycolysis and PER1, combined with trastuzumab at ZT6, significantly improved trastuzumab efficacy in gastric cancer. Collectively, these data introduce the circadian clock into trastuzumab therapy and propose a potentially effective chronotherapy strategy to reverse trastuzumab resistance in gastric cancer. SIGNIFICANCE: In trastuzumab-resistant HER2-positive gastric cancer, glycolysis fluctuates with a circadian oscillation regulated by the BMAL1-CLOCK-PER1-HK2 axis, which can be disrupted with a metformin-based chronotherapy to overcome trastuzumab resistance.

CD146 Associates with Gp130 to Control a Macrophage Pro-inflammatory Program That Regulates the Metabolic Response to Obesity.

The mechanism of obesity-related metabolic dysfunction involves the development of systemic inflammation, largely mediated by macrophages. Switching of M1-like adipose tissue macrophages (ATMs) to M2-like ATMs, a population of macrophages associated with weight loss and insulin sensitivity, is considered a viable therapeutic strategy for obesity-related metabolic syndrome. However, mechanisms for reestablishing the polarization of ATMs remain elusive. This study demonstrates that CD146+ ATMs accumulate in adipose tissue during diet-induced obesity and are associated with increased body weight, systemic inflammation, and obesity-induced insulin resistance. Inactivating the macrophage CD146 gene or antibody targeting of CD146 alleviates obesity-related chronic inflammation and metabolic dysfunction. Macrophage CD146 interacts with Glycoprotein 130 (Gp130), the common subunit of the receptor signaling complex for the interleukin-6 family of cytokines. CD146/Gp130 interaction promotes pro-inflammatory polarization of ATMs by activating JNK signaling and inhibiting the activation of STAT3, a transcription factor for M2-like polarization. Disruption of their interaction by anti-CD146 antibody or interleukin-6 steers ATMs toward anti-inflammatory polarization, thus attenuating obesity-induced chronic inflammation and metabolic dysfunction in mice. The results suggest that macrophage CD146 is an important determinant of pro-inflammatory polarization and plays a pivotal role in obesity-induced metabolic dysfunction. CD146 could constitute a novel therapeutic target for obesity complications.

Risk factors affect accurate prognosis in ASXL1-mutated acute myeloid leukemia.

BACKGROUND: The epigenetic regulator additional sex combs-like 1 (ASXL1) is an adverse prognostic factor in acute myeloid leukemia (AML). However, the mutational spectrum and prognostic factors of ASXL1-mutated (ASXL1+) AML are largely unknown. We aim to evaluate the risk factors influencing the prognosis of ASXL1+ AML. METHODS: We performed next-generation sequencing (NGS) in 1047 cases of de novo AML and discovered 91 ASXL1+ AML (8.7%). The Log-Rank test and Kaplan-Meier were used to evaluate survival rate, and the Cox regression model was used to analyze multivariate analysis. RESULTS: In a total of 91 ASXL1+ AML, 86% had one or more co-mutations. The factors that had adverse impact on overall survival (OS) and event-free survival (EFS) are defined as high risk factors, including age ≥ 60 years, WBC count ≥ 50 × 109/L, FLT3-ITD mutations, RUNX1 mutations, and absence of AML1-ETO fusion gene. ASXL1 mutations without any risk factor were classified as single-hit ASXL1+ AML; ASXL1 mutations accompanied with one of the risk factors was referred to as double-hit ASXL1+ AML; ASXL1 mutations with two or more of the risk factors were designated as triple-hit ASXL1+ AML. The combination of these risk factors had a negative influence on the prognosis of ASXL1+ AML. The median OS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 6.67 months in triple-hit ASXL1+ AML (P = 0.003). The median EFS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 5.47 months in triple-hit ASXL1+ AML (P = 0.002). Allogenic hematopoietic stem cell transplantation (allo-HSCT) improved the prognosis of double/triple-hit ASXL1+ AML patients. CONCLUSIONS: Our study provided new insights into the mutational spectrum and prognostic factors of ASXL1+ AML patients. Our primary data suggest that the risk factors in ASXL1+ AML contribute to the poor outcome of these patients. The management of ASXL1+ AML patients should be based on the risk factors and allo-HSCT is highly recommended for consolidation.

Single-cell analysis of a tumor-derived exosome signature correlates with prognosis and immunotherapy response.

BACKGROUND: Tumor-derived exosomes (TEXs) are involved in tumor progression and the immune modulation process and mediate intercellular communication in the tumor microenvironment. Although exosomes are considered promising liquid biomarkers for disease diagnosis, it is difficult to discriminate TEXs and to develop TEX-based predictive biomarkers. METHODS: In this study, the gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) database, IMvigor210 cohorts, and six independent Gene Expression Omnibus datasets. A TEXs-associated signature named TEXscore was established to predict overall survival in multiple cancer types and in patients undergoing immune checkpoint blockade therapies. RESULTS: Based on exosome-associated genes, we first constructed a tumor-derived exosome signature named TEXscore using a principal component analysis algorithm. In single-cell RNA-sequencing data analysis, ascending TEXscore was associated with disease progression and poor clinical outcomes. In the TCGA Pan-Cancer cohort, TEXscore was elevated in tumor samples rather than in normal tissues, thereby serving as a reliable biomarker to distinguish cancer from non-cancer sources. Moreover, high TEXscore was associated with shorter overall survival across 12 cancer types. TEXscore showed great potential in predicting immunotherapy response in melanoma, urothelial cancer, and renal cancer. The immunosuppressive microenvironment characterized by macrophages, cancer-associated fibroblasts, and myeloid-derived suppressor cells was associated with high TEXscore in the TCGA and immunotherapy cohorts. Besides, TEXscore-associated miRNAs and gene mutations were also identified. Further experimental research will facilitate the extending of TEXscore in tumor-associated exosomes. CONCLUSIONS: TEXscore capturing tumor-derived exosome features might be a robust biomarker for prognosis and treatment responses in independent cohorts.