Background: In cancer, the process of anoikis is intimately associated with the emergence and progression. N6-methyladenosine modification and m6A modification play an important role in regulating long non-coding RNAs. The liver hepatocellular carcinoma patients' data, including clinical and prognostic data, were obtained via The Cancer Genome Atlas database. The univariate, multivariate Cox and Least Absolute Selection Operator (LASSO) regression were performed to gain anoikis- and m6A-related lncRNAs. The Kaplan-Meier method was employed to assess the overall survival rate for groups of high- and low risks. Results: A signature comprising six anoikis- and m6A-related lncRNAs was constructed: AL117336.3, LINC01138, Z83851.1, NRAV, CASC19 and AC009283.1. The clinicopathological variables, the anoikisand m6A-related lncRNA signature demonstrated superior diagnostic efficacy, with an area under the receiver operating characteristic curve of 0.810. In the high-risk group, the overall survival was shown to be inferior to that of in group of low risk, while patients were classified by distinct clinicopathological variables. The ssGSEA and CIBERSORT immune analysis demonstrated that the predictive signature was significantly associated with liver cancer patients' immune status. The chemotherapy drugs ATRA, AUY922, bexarotene, gemcitabine, mitomycin-C, and PHA have been found to have greater sensitivity in treating high-risk patients. qRT-PCR showed that Z83851.1, NRAV and CASC19 lncRNAs were associated with poor prognosis and were high-risk factors. AC009283.1 lncRNA may have anti-cancer properties. Conclusions: The predictive signature is capable of independently predicting the prognosis of liver cancer patients for understanding the mechanisms of anoikis- and m6A-related lncRNAs in liver hepatocellular carcinoma and offering clinical guidance to patients with liver cancer. How to cite: Yu P, Jing S, Dhillon SK. Anoikis and m6A related lncRNAs analysis to identify prognostic indicators in liver hepatocellular carcinoma. Electron J Biotechnol 2026;79. https://doi.org/10.1016/j.ejbt. (c) 2025 The Author(s). Published by Elsevier Inc. on behalf of Pontificia Universidad Cat oe lica de Valpara & Uacute;so. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/

Background Tiao-Shen-Zhi-Ai Formula (TSZAF) is a compound prescription of traditional Chinese medicine used clinically for the treatment of ovarian cancer. In this study, we selected three main active ingredients from TSZAF and combined them into a new TSZAF monomer combination (TSZAF mc) to investigate its effects and mechanisms on inhibiting ovarian cancer proliferation and inducing apoptosis. Methods The effects of TSZAF mc on proliferative activity and apoptosis in ovarian cancer HEY and SKOV3.IP1 cells were assessed in vitro using CCK-8 assay, colony formation assay, and apoptosis assay. Micromethods, flow cytometry, and immunofluorescence were employed to evaluate the impact of TSZAF mc on aerobic glycolytic metabolites and mitochondrial membrane potential. The mRNA and protein expression of key glycolytic genes were detected by quantitative real-time PCR (RT-PCR) and Western blot (WB). An ovarian cancer subcutaneous tumor model was established in NOD-SCID mice using SKOV3.IP1 cells. TSZAF mc was administered via continuous intraperitoneal injection, and its antitumor efficacy in vivo was assessed through anatomical observation, hematoxylin and eosin (H&E) staining, and immunohistochemistry (IHC). Further RT-PCR, WB, and IHC were performed to validate the expression of key upstream glycolytic genes at mRNA and protein levels. Drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA) were used to confirm binding targets. Molecular docking was performed to predict the binding interactions between the monomers and AKT. Finally, the regulatory relationships within signaling pathways were elucidated based on functional assays. Results TSZAF mc effectively inhibited ovarian cancer proliferation and induced apoptosis. It reduced lactate and ATP production, downregulated mitochondrial membrane potential, and decreased the mRNA and protein expression of key glycolytic genes, including HK2, PKM2, PFKM, GLUT1, and LDHA. In vivo, TSZAF mc suppressed ovarian cancer growth. Moreover, TSZAF mc downregulated the expression of phosphorylated AKT (p-AKT) and phosphorylated FOXO3A (p-FOXO3A) at both protein and tissue levels. CETSA and DARTS demonstrated that TSZAF mc binds AKT. The AKT activator SC79 reversed the inhibitory effects of TSZAF mc on ovarian cancer proliferation and the downregulation of glycolytic proteins. Conclusion TSZAF mc inhibits ovarian cancer progression by regulating the AKT/ FOXO3A-mediated glycolysis pathway, which may represent one of the mechanisms underlying the clinical efficacy of TSZAF in ovarian cancer treatment.

ObjectiveTo develop an early postoperative rehabilitation nursing protocol for patients with peritoneal cancer following cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), and to evaluate its effectiveness.MethodsA total of 177 patients with peritoneal cancer who underwent CRS combined with HIPEC at Beijing Tsinghua Changgung Hospital, Tsinghua University from January to October 2024 were randomly assigned to control group and observation group by random number table method, with 94 and 83 cases in each group, respectively. The control group received conventional rehabilitation nursing, including basic daily care, position management, pulmonary function rehabilitation (once every two hours, twice daily, 10-15 minutes per session), bedside activities (30 minutes per session, twice daily, seven days per week), lasting for two weeks. The observation group additionally received early postoperative rehabilitation nursing protocol, targeting the improvement of postoperative dysfunction after CRS combined with HIPEC, including aerobic exercise, resistance exercise, and balance training, 60 minutes per session, twice daily, seven days per week, lasting for two weeks. Before intervention and one day prior to discharge, the Short Physical Performance Battery (SPPB) was used to evaluate physical performance by researchers blinded to group allocation; De Morton Mobility Index (DEMMI) was used to evaluate physical activity and mobility; Borg Rating of Perceived Exertion (RPE) was used to evaluate subjective fatigue; Barthel Index (BI) was used to evaluate activities of daily living; Six-Minute Walking Test (6MWT) was used to evaluate cardiopulmonary function; a pulse oximeter was used to measure blood oxygen saturation (SpO2); and a portable spirometer was used to measure forced vital capacity (FVC). The incidence of postoperative adverse events, including atelectasis, deep vein thrombosis, intestinal obstruction, arrhythmia, and falls, as well as postoperative hospital stay duration and gastric tube retention time were compared between two groups.Results(1) SPPB, DEMMI, RPE and BI scores: compared with that before intervention, SPPB, DEMMI, and BI scores in both groups increased significantly after intervention (P<0.05), while RPE score decreased significantly (P<0.05). Compared with the control group, SPPB, DEMMI, and BI scores in the observation group were significantly higher after intervention (P<0.05), while the RPE score was significantly lower (P<0.05). (2) SpO2, 6MWT and FVC: compared with that before intervention, SpO2 and 6MWT in both groups increased significantly after intervention (P<0.05), and FVC in the observation group increased significantly after intervention (P<0.05). Compared with the control group, SpO2, 6MWT and FVC scores in the observation group were significantly higher after intervention (P<0.05). (3) Postoperative hospital stay and gastric tube retention time: compared with the control group, postoperative hospital stay and gastric tube retention time in the observation group were significantly shorter (P<0.05). (4) Incidence of adverse events: there was no statistically significant difference in the incidence of adverse events between two groups (P>0.05).ConclusionThe early postoperative rehabilitation nursing protocol can effectively facilitate physical functional recovery and improve cardiopulmonary function in patients who underwent CRS combined with HIPEC, as well as reduce hospital stay duration and gastric tube retention time.

ObjectiveTo explore the prevalence of depressive symptoms in postoperative patients with ovarian cancer and to analyze its influencing factors from multiple dimensions, including clinical characteristics, psychological factors, and laboratory indicators. MethodsA cross-sectional study was conducted, which enrolled 235 postoperative patients with ovarian cancer. Depressive status was assessed using the patient health questionnaire, and the demographic, pathological, and medical record data of the patients were collected using the generalized anxiety disorder scale, Pittsburgh sleep quality index, European organization for research and treatment of cancer quality of life questionnaire core 30, and ECOG performance status score. Peripheral blood tumor marker (CA125), routine blood test, lymphocyte subsets, and serum cytokine levels were measured. Univariate and multivariate binary logistic regression analysis were used for statistical analysis. ResultsThe prevalence of depression in postoperative patients with ovarian cancer was 39.15% (92/235). Univariate analysis showed that ECOG score ≥ 2 points, pain, anxiety, poor sleep quality, low quality of life, low life satisfaction, tumor recurrence, six or more cycles of chemotherapy, as well as higher levels of CA125, NLR, and NAR, and lower hemoglobin levels were significantly associated with depression (all P<0.05). Multivariate binary Logistic regression analysis showed that anxiety (OR=1.975, 95%CI: 1.231-3.170), sleep efficiency (OR=4.181, 95%CI: 1.211-14.43), sleep latency (OR=34.806, 95%CI: 4.258-284.542), ECOG performance status score, cognitive function (OR=0.918, 95%CI: 0.868-0.97), and life satisfaction were independent risk factors for depression (all P<0.05). Laboratory indicators were not independent influencing factors in the multivariate Logistic regression model. ConclusionDepression in postoperative patients with ovarian cancer is influenced by physiological, psychological, and social factors. Clinical management should focus on patients with anxiety, sleep disorders, poor physical condition, and low life satisfaction, and a comprehensive prevention and treatment strategy centered on psychological intervention and taking into account symptom management and social support should be implemented.

To compare the effects of multikinase inhibitors (sorafenib/lenvatinib) and immune checkpoint inhibitors (PD-1/PD-L1) on anxiety, depression, and quality of life (QoL) in patients with advanced hepatocellular carcinoma (HCC) and to analyse their correlations with clinical indicators. This retrospective cohort study included 304 patients with advanced HCC (BCLC stage B/C) who received first-line monotherapy between 2018 and 2023. Propensity score matching (1:1) was used to categorize patients into two groups: those treated with multikinase inhibitors (n = 152) and those treated with PD-1/PD-L1 inhibitors (n = 152). Anxiety and depression (Hospital Anxiety and Depression Scale (HADS)), and QoL (EORTC QLQ-C30) were assessed at baseline and during follow-up (every 3 months). Correlations between the treatment duration, survival outcomes, and adverse events (AEs) were analysed. The PD-1/PD-L1 group presented significant reductions in anxiety (HADS-A: mean difference [MD] = − 2.4) and depression (HADS-D: MD = − 2.3) at 6 months (both *p < 0.001), with lower rates of clinically significant anxiety (28.3% vs. 42.1%) and depression (24.3% vs. 38.8%; p < 0.05). QoL improved markedly (6-month MD = + 10.3, p < 0.001), particularly when the treatment was administered as the first-line therapy (MD = + 14.2 vs. second-line MD = + 3.8; interaction p < 0.001). PD-1/PD-L1 inhibitors were associated with longer treatment durations (median 9.5 vs. 5.8 months, p < 0.001) and superior overall survival (median 18.2 vs. 12.5 months; HR = 0.62, p = 0.002). Fatigue (grade ≥ 2) independently predicted depression (OR = 1.82, p = 0.002), whereas immune-related AEs were correlated with a reduced QoL (ρ=−0.22, p = 0.004). Compared with multikinase inhibitors, PD-1/PD-L1 inhibitors significantly improve the psychological outcomes, QoL, and survival of patients with advanced HCC, especially when administered as first-line therapies. Fatigue is a critical modifiable risk factor for depression. These findings support prioritizing immunotherapy when treating atients with advanced hepatocellular carcinoma.

Background:While curative-intent resection for gallbladder cancer (GBC) is being increasingly performed in elderly patients, perioperative morbidity and long-term oncological outcomes in this population remain unclear. Methods:Consecutive patients with GBC who underwent curative-intent resection (2016-2020) were identified from a multicentre database and stratified as elderly (>70 years) or younger (≤70 years). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to minimise selection bias. The outcomes compared included overall survival (OS), cancer-specific survival (CSS) and short-term outcomes. Logistic regression was used to identify risk factors for major morbidity and Cox regression was used for CSS, with the Fine-Gray competing risk model further applied to account for non-cancer-related death in the analysis of CSS. Results:Among the 575 patients enrolled, 432 were younger and 143 were elderly. After 1:1 PSM and IPTW, elderly patients had significantly higher 90-day major morbidity rates than younger patients (p=0.029 and p=0.010, respectively), but also demonstrated better CSS in both cohorts (p=0.038 and p<0.001, respectively). OS was significantly longer in elderly patients only after PSM (p<0.001), with no significant difference after IPTW (p=0.684). Multi-adjusted analysis confirmed that advanced age was an independent risk factor for major morbidities (original cohort: OR 1.71 (95% CI 1.12 to 2.59); PSM: OR 1.88 (95% CI 1.08 to 3.30); IPTW: OR 1.83 (95% CI 1.17 to 2.82)) but was associated with longer CSS (original cohort: HR 0.65 (95% CI 0.44 to 0.97); PSM: HR 0.29 (95% CI 0.18 to 0.45); IPTW: HR 0.62 (95% CI 0.42 to 0.90); Fine-Gray model: HR 0.34 (95% CI 0.30 to 0.39)). Conclusion:Despite a higher risk of major postoperative morbidity, advanced age itself might not be considered a contraindication for curative-intent resection. Selected elderly patients with GBC may achieve superior CSS compared to their younger counterparts.

Lung cancer remains the leading cause of cancer-related death globally, with metastasis driven by circulating tumor cells (CTCs)-particularly clusters-being a major treatment challenge. Despite their critical role, the biological differences between single CTCs and CTC clusters remain unclear. Here, we comprehensively compared their behavioral, transcriptomic, and proteomic profiles in lung cancer models. Compared with single cells, CTC clusters present enhanced metastatic potential, greater survival in the bloodstream and increased resistance to microenvironment. Mechanistically, the Src/FN1 pathway is centrally activated in clusters, promoting intercellular cohesion and protecting against immune clearance and stress in circulation. Pharmacological inhibition of Src with the clinical inhibitor KX2-391 disrupted clustering, impaired CTC survival, and reduced metastasis in preclinical models. Our findings identify the Src/FN1 pathway as a key vulnerability in CTC cluster-driven metastasis, suggesting that Src inhibitors are promising therapeutic strategies to disrupt clustering and improve outcomes in patients with metastatic lung cancer.

Supplementary Fig. S5 In co-culture with macrophages, TRAF3IP2-AS1 deficiency-induced necroptosis promotes the enhancement of EMT via the secretion of TGFβ1.

Background:Hepatocellular carcinoma (HCC) is the second leading cause of death globally. Furthermore, HCC patients have poor long-term survival following curative resection because of a high rate of tumor recurrence. Little is known about the genomic trajectory from primary to early recurrent HCC. The HCC patient survival rate has improved because of improved diagnostic protocols. Increasing numbers of lncRNAs have been revealed to be involved in the carcinogenesis and progression of HCC. Among them, The aim of our study was to examine the prognostic value of Loxl1-As1 expression in patients with HCC. Methods:In this study, we analyzed Loxl1-As1 expression in HCC using tissue microarray and fluorescence in situ hybridization. The expression of lncRNA Downregulated in metastatic HCC (Loxl1-As1) in cell lines and tissues was detected by quantitative real-time polymerase chain reaction and in situ hybridization (ISH); cell counting kit-8, colony formation, and flow cytometry were performed to investigate the role of Loxl1-As1 in HCC cell proliferation, cell cycle progression, and apoptosis in vitro; migration was investigated in HCC cell lines in vitro; and Western blot was used to detect the downstream of Loxl1-As1. Results:Clinically, Loxl1-As1 correlated with poor prognosis of HCC. Loxl1-As1 was downregulated in HCC tissues and cell lines. The ISH assay revealed that Loxl1-As1 expression was significantly decreased in 177 paraffin-embedded samples from patients with HCC compared with non-tumor tissues and Loxl1-As1 expression directly correlated with patient prognosis. In vitro studies indicated that Loxl1-As1 promoted the proliferation and clonogenicity of HCC cells and the expression of Loxl1-As1 suppressed the growth, migration, and metastasis of HCC cells in vitro. Conclusions:Collectively, the findings demonstrate that Loxl1-As1 is over-expressed in HCC patients and associated with a poor prognosis. Additionally, Loxl1-As1 plays an important role in HCC progression. These findings support the notion that lncRNA Loxl1-As1 might be a new driver biomarker and future therapeutic target for HCC patients.

Gastrointestinal stromal tumors (GISTs) represent the most common mesenchymal neoplasms of the gastrointestinal tract and are typically associated with activating mutations in the kinase insert domain receptor (c-KIT) or platelet-derived growth factor receptor alpha. The advent of targeted therapies, such as imatinib, has substantially improved clinical outcomes; however, primary double-mutant GISTs present significant therapeutic challenges. We report the case of a 51-year-old man who presented with a 2-week history of left upper abdominal pain and melena. Contrast-enhanced abdominal computed tomography revealed a mass in the pelvic region of the small intestine. Histopathological analysis demonstrated a spindle cell morphology with a high mitotic index. Immunohistochemical staining was positive for CD117, CD34, and Dog-1, confirming the diagnosis of a high-risk small intestinal GIST. At the time of diagnosis, genetic testing was not performed, and the patient was initiated on imatinib therapy. After 5 years of treatment, the patient developed clinical resistance. First-generation sequencing identified concurrent mutations in c-KIT exons 11 (V560D) and exon 17 (N822K), implicating these double mutations in acquired imatinib resistance. This case underscores the clinical significance of double mutations in GIST, the limitations of first-line therapy in such contexts, and the importance of early genetic profiling to inform personalized treatment strategies.

Supplementary Fig. S3 TRAF3IP2-AS1 deficiency leads to necroptosis in PDAC.

Supplementary Fig. S8 TRAF3IP2-AS1 deficiency induces necroptosis in human PDAC through the synergistic action of IGF2BP2 and PPM1B

Supplementary Table S3 Characteristics of the organoids from the External Cohort

Metastasis is a key cause of death in tumor patients,and a number of tumor patients have comorbid psychosomatic abnormalities and are in a state of chronic stress.Chronic stress affects the release of many kinds of hormones and neurotransmitters,such as epinephrine,norepinephrine,dopamine,glucocorticoids,cortisol,sex hormones,etc.,through the hypothalamus-pituitary-adrenal axis and sympathetic nervous system.These substances can act on the β-adrenergic receptor,glucocorticoid receptor,etc.,on tumor cells,immune cells,and other cells in the tumor microenvironment and promote the tumor progression and metastasis by directly enhancing the invasive and metastatic ability of tumor cells,inducing the formation of the immunosuppressive microenvironment and promoting tumor angiogenesis and other pathways.Antip-sychotic drugs,β-blockers,and glucocorticoid receptor antagonists have inhibitory effects on chronic stress-mediated tumor metastasis and have achieved certain clinical efficacy.Relevant studies have been carried out on traditional Chinese medicine decoctions and monomers,which can inhibit tumor metastasis by modulating the immune microenvironment and reversing chronic stress-mediated hormonal changes.The psychological problems of tumor patients have gradually received attention,and the development of new anti-metastatic drugs based on the mechanism of action of chronic stress in promoting tumor progression and metastasis provides new ideas for the improvement of the overall efficiency of tumor prevention and treatment.

Combination chemotherapy and immunotherapy have failed to achieve breakthroughs in pancreatic ductal adenocarcinoma (PDAC). Chemotherapy-induced senescence is a potential solution for this problem. This study integrates clinical samples with single-cell transcriptomic sequencing, proteomics, and RNA sequencing and reveals that FOLFIRINOX (a combination regimen of 5-fluorouracil, oxaliplatin, irinotecan, and leucovorin) treatment induces a higher proportion of senescent tumor cells (senTCs). This phenomenon is principally attributed to the presence of cCCT2, which inhibits SLX4 condensate-mediated DNA damage repair pathways by regulating small ubiquitin-like modifier conjugation, thereby promoting tumor cell senescence. In the tumor immune microenvironment, cCCT2-overexpressing senTCs exhibit a senescence-associated secretory phenotype (SASP) with preferential secretion of CXCL10, which induces chemotaxis of CD8+ T-cells. Based on the pro-senescence and immune-microenvironment-remodeling effects of cCCT2, an engineered exosome-loaded circRNA system, SenExo-cCCT2 is developed. When combined with SenExo-cCCT2, the FOLFIRINOX regimen enhances the capacity of pancreatic cancer cells to induce senescence. Subsequently, anti-PD-L1 therapy facilitates the immune-mediated clearance of senTCs, markedly improving the therapeutic efficacy of combined chemotherapy and immunotherapy for pancreatic cancer.

Supplementary Fig. S7 TRAF3IP2-AS1 deficiency regulates PPM1B ubiquitination through TRAF3IP2

Locating tumors during laparoscopic surgery for early gastric cancers poses an important challenge because they lack involvement with the serosal layer and remain invisible within the peritoneal cavity. To address this issue, various techniques such as preoperative dye injection and magnetic clip detection systems have been introduced to aid in intraoperative tumor localization. However, these existing techniques are often intricate and lack intuition and endurance. In this study, we propose a novel approach utilizing fluorescent soft robots to accurately locate tumors within the stomach. The methodology involved placing a metal clip at the tumor site, followed by administering several soft robots labeled with Cy5. These soft robots were designed to autonomously converge around the metal clip. To validate their efficacy, we conducted animal experiments by implanting clips into the stomachs of rats and subsequently administering capsules containing the soft robots. By detecting the resulting fluorescence, we successfully identified the location of the clips within the stomach. Our findings indicate that these soft robots hold great promise as a viable alternative for localizing gastric lesions during laparoscopic surgery, which has better persistence and intuitiveness than other markup methods. Their implementation could significantly enhance the accuracy and efficiency of tumor identification in a technologically advanced and clinically accessible manner.

Metastasis remains the primary cause of cancer-related mortality worldwide. Circulating tumor cells (CTCs) represent critical targets for metastasis prevention and treatment. Traditional Chinese medicine may prevent lung cancer metastasis through long-term intervention in CTC activity. Tiao-Shen-Zhi-Ai Formular (TSZAF) represents a Chinese medicine compound prescription utilized clinically for lung cancer treatment. This study combined three principal active ingredients from TSZAF into a novel TSZAF monomer combination (TSZAF mc) to investigate its anti-metastatic effects and mechanisms. TSZAF mc demonstrated significant inhibition of proliferation, migration, and invasion in CTC-TJH-01 and LLC cells, while inducing cellular apoptosis in vitro. Moreover, TSZAF mc substantially inhibited LLC cell growth and metastasis in vivo. Mechanistically, TAZSF mc significantly suppressed the Wnt/β-catenin signaling pathway and CXCL5 expression in lung cancer cells and tissues. Additionally, TAZSF mc notably reduced neutrophil infiltration in metastatic lesions. These findings indicate that TSZAF mc inhibits lung cancer growth and metastasis by suppressing the Wnt/β-catenin signaling pathway and reducing CXCL5 secretion, thereby decreasing neutrophil recruitment and infiltration. TSZAF mc demonstrates potential as an effective therapeutic agent for lung cancer metastasis.

BACKGROUND Genetic screening for breast cancer gene 1 (BRCA )1 /2 mutations can inform breast/ovarian/pancreatic cancer patients of suitable therapeutic interventions. Four to seven percent of pancreatic cancer patients have germline BRCA mutations. BRCA genes aid in DNA repair, especially homologous recombination, which impacts genomic stability and cancer cell growth. BRCA1 regulates the cell cycle, ubiquitination, and chromatin remodeling, whereas BRCA2 stimulates the immune response. They predict the efficacy of platinum chemotherapy or polymerase (PARP) inhibitors such as olaparib. AIM To determine the trends and future directions in the use of olaparib for pancreatic cancer treatment. METHODS To evaluate the trends in how olaparib works in pancreatic cancer, we performed a bibliometric analysis. One hundred and ninety-six related publications were accessed from the Web of Science Core Collection and were published between 2009 and 2022. The analytic parameters included publications, related citations, productive countries and institutes, influential authors, and keyword development. RESULTS This study visualizes and discusses the current research, including the present global trends and future directions in olaparib and pancreatic cancer. Overall, this study sheds light on optimizing the use of olaparib in pancreatic cancer treatment, offering valuable guidance for researchers in this field. CONCLUSION Our findings identified trends in olaparib and pancreatic cancer, with China and the USA leading and with global cooperation tightening. O'Reilly EM's team and Memorial Sloan-Kettering had the highest output. The Journal of Clinical Oncology was the most cited journal. More PARP inhibitors are emerging, and combination therapy is suggested for future therapeutic trends.