Infratentorial brain metastases (BMs) are life-threatening because of the unique anatomical features and physiological functions of the posterior cranial fossa. However, the comparative prognosis of infratentorial BM and supratentorial BM remains poorly understood. We conducted a matching comparison of the prognosis between non-small cell lung cancer (NSCLC) patients with and without infratentorial BM and analyzed prognostic factors, including the radiotherapy (RT) method. 392 NSCLC patients who underwent brain RT from July 2010 until June 2023 were analyzed. After 1:1 propensity matching, we compared 115 patients with only supratentorial BMs (supraT-alone group) and 115 patients with infratentorial ± supratentorial BMs (infraT ± supraT group). We assessed intracranial control and overall survival (OS) using Kaplan-Meier and Cox regression. There was no statistical difference for extracranial progression-free survival (PFS), intracranial local PFS, or distant PFS. The supraT-alone group had significantly better OS (median: 35.3 vs. 24.2 months, p = 0.021). The supraT-alone group in the multivariate analysis had BM resection (p = 0.031), targeted therapy (p < 0.001), and immune therapy (p = 0.006) associated with improved OS. The infraT ± supraT group had RT method (p = 0.002), ≤ 60 years of age (p = 0.002), targeted therapy (p = 0.017), and number of extracranial metastases (p < 0.001) when reporting OS. We confirmed that WBRT+boost and SRT improved OS compared to WBRT alone. There was no statistical difference in OS for WBRT+boost and SRT. The overall grade 3-4 acute toxicities were similar for both groups. Our study suggests that infratentorial BMs in NSCLC lead to worse OS. However, local high-dose RT strategies (SRT or WBRT+boost) may confer survival benefits to patients who present with infratentorial involvement.

Hepatic arterial infusion chemotherapy using a combination of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) has shown promise for patients with advanced-stage hepatocellular carcinoma (HCC). In this study, we aim to evaluate the efficacy and safety of combining adebrelimab (anti-PD-L1 antibody) and bevacizumab with HAIC-FOLFOX for HCC patients in BCLC stage C. This retrospective study included 32 untreated advanced-stage HCC patients receiving HAIC-FOLFOX combined with adebrelimab and bevacizumab as first-line therapy. The primary endpoint is overall response rate (ORR) based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. From January 14th, 2024, to December 5th, 2024, a total of 32 patients received the triplet combination of HAIC-FOLFOX, adebrelimab, and bevacizumab. Median follow-up time was 6.1 months. According to RECIST v1.1 criteria, the confirmed ORR was 71.8% (95% CI: 55.4-88.3 %), with a disease control rate (DCR) of 93.7% (95% CI: 84.9-99.9%). Only one case (3.1%) had a grade 3 treatment-related adverse event (rash), which could be alleviated after symptomatic management. The combination of adebrelimab, bevacizumab, and HAIC-FOLFOX demonstrated encouraging results and manageable safety concerns for patients with HCC at BCLC stage C.

Small cell lung cancer (SCLC) has a dismal prognosis with a low 2-year survival rate. Chemotherapy for recurrent SCLC fails invariably, and novel tumor targets are needed. Here, the effects of agents targeting the peroxisome proliferator-activated receptors (PPARs) in SCLC are investigated. Initial screening of 96 PPAR-directed agents was performed in two SCLC CTC-derived lines (BHGc10, BHGc16). Compounds showing high cytotoxicity were subsequently tested in two pleural effusion-derived lines (S457, S1392) and the SCLC line NCI-H69. Several PPARs emerged as actionable targets: eight PPARγ ligands and nine ligands for PPARα, PPARα/δ, or PPARβ/δ. For the six most effective compounds, treatment-induced protein changes were further profiled in BHGc16 using protein arrays. Cytotoxicity varied by compound, while the PPARγ agonist pioglitazone and the PPARα agonist fenofibrate were preferentially active in CTC lines, DG172 hydrochloride was selective for pleural effusion-derived lines, while rosiglitazone maleate, cloxiquine, and agrimol B showed no selectivity. Mechanistically, in the CTC-derived cell line BHGc16, these six PPAR-directed agents increased pro-apoptotic proteins (Bax, Bad, caspase-3/9), decreased anti-apoptotic and invasion proteins (Bcl-2, Bcl-XL, c-FLIP-L, ICAM-1, CXCR4), and suppressed Akt/mTOR, MEK/ERK, p38 MAPK, and JAK2/STAT3 signaling. These findings support PPARs as clinically relevant targets in SCLC, with PPAR-directed agents showing cytotoxic effects comparable to those reported in other malignancies. Such agents may aid SCLC treatment and help delineate biological differences between CTCs and resident tumor cells.

The progression of cancer strongly depends on the tumor microenvironment and immune surveillance. Tumor necrosis factor alpha (TNFα), a key inflammatory cytokine, can drive both tumor elimination and promotion, depending on its dose and the type of cancer. Colorectal cancer cell lines HCT 116, HT-29, and melanoma cells A375 engineered to stably overexpress the human TNFα gene were used to induce experimental subcutaneous tumors in two immunodeficient mouse strains: athymic Balb/c-nu/nu and SCID/bg mice. In athymic mice, TNFα-overexpressing cells completely lost their tumorigenicity. In SCID/bg mice, with no mature T and B cells and defective NK cells, the TNFα-overexpressing cells formed rudimentary flat ulcerous xenografts with rapidly reduced size, with tumor penetrance of 50-85%. Histopathological analysis revealed necrotic lesions, a more differentiated phenotype of tumor cells forming pseudoglandular structures, and more abundant stromal cells. Intratumoral infiltration of immune cells increased in TNFα-secreting tumors. Positivity of cytokeratins 7 and 20 in colorectal cancer xenografts was decreased. Paradoxically, the expression of ALDH1A1 and ALDH1A3 isoforms, which are important for disease prognosis, was increased. Our study suggests that careful modulation of the tumor microenvironment to a tumor-suppressive one using cytokine TNFα and controlled stimulation of antitumor immunity can contribute to the improvement of cancer treatment.

Gastric cancer is one of the most common and deadliest malignancies worldwide. Better knowledge of the risk factors for gastric cancer is essential for risk classification and therapeutic strategy evolution in gastric cancer patients. Many kinds of miRNA clusters participate in tumorigenesis and tumor progression. Herein, we sought to screen and certify the crucial miRNA cluster for prognosis prediction and potential therapeutic targets in gastric cancer. The results showed that the mir-371a-373 cluster was the most highly expressed miRNA cluster in gastric cancer. The high expression of the mir-371a-373 cluster (mir-371a, mir-372, and mir-373) was positively associated with the poor overall survival of gastric cancer patients. The expression of mir-373 was correlated with early gastric cancer recurrence. mir-373 was an independent risk factor for gastric cancer recurrence and mortality. Then, gain- and loss-of-function experiments demonstrated that mir-373 could promote the malignancy of gastric cancer cells in vitro and in vivo. Through bioinformatics analysis and experimental validation, mir-373 was correlated with tumor regulation, and ZFP91 was the direct target of mir-373. Our findings suggest that the miR-371-373 cluster, especially mir-373, could be a robust marker for the prognosis prediction of gastric cancer and a potential therapeutic target for gastric cancer.

In this study, we investigated the development and application of patient-derived xenograft (PDX) models for metastatic breast carcinoma. Orthotopic PDX models were established from tumor tissue of invasive ductal breast carcinoma patients without prior neoadjuvant therapy. Following successful tumor engraftment in immunodeficient NOD SCID gamma (NSG) mice, primary tumors were surgically excised using a procedure simulating radical mastectomy, enabling extended post-operative survival for the development of eventual metastases. Tumor growth, the presence of lung metastases, along with their histopathological features and immunohistochemical profiles, were evaluated. Three stable and transplantable PDX models were successfully established. Spontaneous lung metastases developed in one model following surgical resection, and this metastatic capability was preserved across multiple in vivo passages. Despite the successful engraftment, significant discrepancies were observed between the immunohistochemical characteristics of the original patient tumors and their corresponding PDXs, particularly in hormone receptor status and Ki-67 proliferation marker expression. These findings highlight the challenges of maintaining molecular fidelity in traditional PDX models.

Radiotherapy (RT) plays a central role in the management of glioblastoma, often in combination with other treatment modalities. While RT can enhance both local and systemic tumor control, especially when used alongside immunotherapy, it is also associated with lymphopenia - a reduction in lymphocyte count - which has been linked to poorer treatment outcomes and reduced survival. This retrospective study aimed to examine the relationship between radiation dose delivered to brain vessels and the severity of lymphopenia in patients with newly diagnosed glioblastoma treated at a tertiary cancer center in 2021. Brain vessels were manually contoured using MRI data, and dose-volume analysis was conducted. Lymphopenia severity was graded according to CTCAE v5.0, and statistical analyses were performed to identify any correlations. Among the 28 patients analyzed, 32% developed grade 1-3 lymphopenia. No significant correlation was found between the radiation dose to brain vessels and the degree of lymphopenia. The median volume of irradiated vessels did not differ significantly between patients with and without lymphopenia. In glioblastoma patients, multiple factors contribute to decreased lymphocyte count - e.g., chemotherapy and corticosteroid use. Although no definitive link was identified, the study underscores the importance of preserving lymphocyte counts during glioblastoma treatment and supports the need for further prospective research to explore strategies like lymphocyte-sparing RT and to better understand the mechanisms behind treatment-related lymphopenia.

Accumulating evidence highlights the critical roles of autophagy-dependent ferroptosis mediators in colorectal cancer (CRC) pathogenesis. To elucidate SIRT6's tumor-suppressive role, HT29 cells stably overexpressing SIRT6 (Oe-SIRT6) were generated via plasmid transfection. Functional assays were performed to evaluate autophagy and ferroptosis. Rescue experiments using the autophagy inhibitor 3-MA or the mTOR agonist MHY1485 were conducted. Quantitative analyses revealed marked downregulation of SIRT6 expression in CRC cell lines (SW620, SW480, and HT29) compared to normal colon epithelial cells. SIRT6 overexpression induced autophagy and activated ferroptosis. The autophagy inhibitor 3-MA blocked SIRT6-driven ferroptosis, which confirmed its dependency on autophagy. Moreover, SIRT6 was found to inactivate mTOR/STAT3 signaling, whereas the mTOR agonist MHY1485 reversed SIRT6 overexpression on autophagy-dependent ferroptosis of CRC cells. Our findings establish SIRT6 as a dual-phase regulator of CRC cell death, suppressing mTOR/STAT3 signaling to orchestrate autophagy-dependent ferroptosis.

WD Repeat Domain 4 (WDR4) is integral to the development and progression of various cancers; however, its specific role and underlying molecular mechanisms in glioma remain inadequately elucidated. This study undertook an analysis of WDR4 expression levels in glioma and normal brain tissues utilizing publicly accessible datasets from TCGA and GTEx project, with further validation conducted through the GEPIA and the HPA databases. Prognostic significance was assessed using Kaplan-Meier survival analysis and multivariate Cox regression models. Cellular functions were investigated through CCK-8 viability assays, colony formation assays, and cell cycle analysis, while the tumorigenic potential in vivo was corroborated using a nude mouse xenograft model. The findings revealed a significant upregulation of WDR4 in both glioma tissues and cell lines. Elevated WDR4 expression correlated with reduced overall survival and emerged as an independent prognostic factor. Functional assays indicated that WDR4 silencing markedly inhibited glioma cell proliferation, induced G1 phase cell cycle arrest, and resulted in the downregulation of CDK1 and CDK2 protein expression. Further co-expression analysis, GSEA, KEGG pathway enrichment, and western blotting suggested that WDR4 may exert its oncogenic effects through activation of the PI3K/Akt signaling pathway. In conclusion, WDR4 is highly expressed in glioma and promotes tumor progression via the PI3K/Akt-CDK1/2 signaling axis. These findings indicate that WDR4 may serve as a potential prognostic biomarker and therapeutic target in glioma.

This corrects the article DOI:10.4149/neo_2025_250411N162.

Salinomycin (Sal), an ionophore antibiotic, has shown promising anti-cancer activity in multiple cancers. In this study, we aimed to investigate the effect of Sal on the ROS/NF-κB/NLRP3 pathway in cholangiocarcinoma (CCA) in vitro and in vivo. We observed that Sal inhibited cell proliferation, migration, and invasion. Sal promoted an increase of Annexin-V positive cells in Huh-28 and RBE cells in a dose-dependent manner, which was efficiently inhibited by VX-765 (Caspase-1 inhibitor), while Sal-induced increase of ROS levels was partially inhibited by exposure to N-acetyl-L-cysteine (ROS scavenger). Moreover, Sal inhibited tumor growth in RBE tumor-bearing mice. The activation of Sal on the ROS/NF-κB/NLRP3 pathway was also identified in CCA cells and tumor tissues. Collectively, these results suggested that Sal activated the ROS/NF-κB/NLRP3 pathway to promote pyroptosis-induced cell death in CCA and suggest it may be a promising treatment strategy for anti-CCA.

Gastric cancer (GC) is a prevalent gastrointestinal malignancy, with metabolic reprogramming, particularly glycolysis, playing a critical role in cancer cell stemness. However, the interaction between glycolysis and GC prognosis, along with its underlying mechanisms, remains poorly understood. This study aimed to systematically analyze the prognostic significance of glycolysis in GC and explore its functional impact. A glycolysis-related gene score was constructed using bioinformatics to assess glycolysis levels based on differentially expressed genes between GC and normal tissues. A nomogram model was developed to predict clinical prognosis, and the functional phenotypes of GC cell lines cultured under high and low glucose conditions were evaluated using metabolite detection and extracellular acidification rate (ECAR) measurements. Enrichment analyses identified key signaling pathways, which were further validated by western blot. Results showed that elevated glycolysis was associated with larger tumor size and poorer prognosis in GC patients. The nomogram demonstrated strong predictive accuracy. High glucose culture promoted glucose consumption, lactate production, ATP generation, and ECAR, enhancing epithelial-mesenchymal transition and malignant progression via the PI3K/AKT pathway. In conclusion, high glycolysis is linked to poor prognosis in GC and drives metastasis and stemness through the PI3K/AKT signaling pathway, highlighting its potential as a prognostic marker and therapeutic target.

Anillin (ANLN), an actin-binding protein, has been implicated in tumorigenesis across various cancers; however, its role in nasopharyngeal carcinoma (NPC) remains largely undefined. In this study, we analyzed ANLN expression using TCGA, CPTAC, and GEO datasets, and confirmed its overexpression in NPC tissues and cell lines through qRT-PCR, western blotting, and immunohistochemistry. High ANLN expression correlated with advanced clinical stage and poor overall survival. Functional assays, including CCK-8 and colony formation, demonstrated that ANLN knockdown suppressed NPC cell proliferation in vitro, while xenograft models confirmed reduced tumor growth in vivo. RNA sequencing and gene set enrichment analysis revealed that ANLN knockdown was associated with downregulation of ribosome biogenesis pathways. Puromycin incorporation assays and transmission electron microscopy further supported impaired protein synthesis and nucleolar disruption following ANLN depletion. These findings suggest that ANLN promotes NPC progression by maintaining ribosome biogenesis and protein synthesis and may serve as a novel prognostic biomarker and therapeutic target.

Brain metastases (BM) are a common and challenging complication of advanced non-small cell lung cancer (NSCLC). This study aimed to evaluate the efficacy and safety of the combination of temozolomide (TMZ) and anlotinib as a second-line treatment in advanced NSCLC patients with BM. Clinical data of advanced NSCLC patients with BM between January 2020 and December 2023 were retrospectively reviewed and analyzed. All patients received TMZ combined with anlotinib as a second-line treatment. The primary endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). A total of 52 patients were enrolled, with 20 females and 32 males. The median PFS and OS were 5.0 months and 10.0 months. The ORR and DCR were 25% and 65%, respectively. Subgroup analysis demonstrated that patients who developed AEs such as hypertension, proteinuria, and hand-foot syndrome, as well as those with a favorable diagnosis-specified graded prognosis assessment score, had better efficacy outcomes, indicating these features may help to identify the priority population for this regimen. Common AEs, including hematological toxicity, fatigue, and hypertension, were generally manageable with dose adjustments and supportive care. TMZ combined with anlotinib could be a safe and effective second-line treatment option for advanced NSCLC patients with BM. Prospective trials are warranted to confirm these findings and optimize the treatment strategy.

This study aimed to evaluate synergistic effects and molecular mechanisms of the histone deacetylase inhibitor chidamide combined with the BCL-2 inhibitor venetoclax in diffuse large B-cell lymphoma (DLBCL) cell lines. Human DLBCL cell lines (U2932, SUDHL-4) were cultured in vitro and treated with chidamide and venetoclax. Cell proliferation inhibition rates were measured using the CCK-8 assay, and IC50 values were calculated. Cells were also treated with a 5:1 combination of chidamide and venetoclax, along with p53 or p21 siRNA. Cell viability, HDAC activity, apoptosis, cell cycle, the amount of p53 and p21 proteins, and BCL-2-BIM binding were analyzed via CCK-8, enzyme activity assays, the Caspase 3/7 Activity Apoptosis Assay Kit, flow cytometry, RT-qPCR, western blot, and co-IP. The binding of p53 and p21 was verified by dual-luciferase reporter assay and chromatin immunoprecipitation. Chidamide and venetoclax exhibited dose- and time-dependent anti-proliferative effects in U2932 and SUDHL-4 cells, with IC50 values of 3.54 μM (chidamide) and 0.67 μM (venetoclax) in the SUDHL-4 cell line and 5.6 μM (chidamide) and 0.91 μM (venetoclax) in the U2932 cell line. Combination treatment significantly enhanced HDAC inhibition, histone H3/H4 acetylation, and p53 expression, leading to increased cell apoptosis. p53 knockdown partially reversed these effects and increased BCL-2/BIM complex formation. The combination also upregulated p53 expression to increase p21 expression, inducing G1/S phase arrest, which was partially reversed by p21 knockdown. To conclude, the chidamide-venetoclax combination synergistically activates the p53-p21 signaling pathway, leading to cell cycle arrest and apoptosis, representing a potential therapeutic strategy for DLBCL.

Gastric cancer (GC) ranks as the fifth most common malignancy globally. Aberrant alternative splicing is implicated in tumorigenesis and progression. SF3B3, a key subunit of the spliceosome complex, is closely linked to alternative splicing dysfunction when its expression is dysregulated. This study delved into SF3B3's role and mechanisms in GC, aiming to uncover novel precision treatment targets. Through TCGA database analysis, SF3B3 was found to be upregulated in GC tissues, associated with poor prognosis and immune infiltration. In vitro experiments included cell culture, transduction, CCK-8, colony formation, scratch, migration, apoptosis assays, cell cycle analysis, and western blot, demonstrating that SF3B3 knockdown curbed GC cell proliferation, migration, and invasion, induced apoptosis and cell cycle arrest, while its overexpression had opposite effects. In vivo xenograft experiments showed that SF3B3 suppression markedly inhibits tumor growth. Transcriptome analysis and western blot suggested that SF3B3 promotes GC cell proliferation and impedes apoptosis by activating the MAPK pathway. Moreover, transcription factor ELK1 was shown to regulate SF3B3 expression, with a significant positive correlation between them. Overall, SF3B3 likely drives GC progression via the ELK1-SF3B3-MAPK axis, representing a potential precision treatment target for GC.

Growing evidence indicates that ferroptosis is pivotal in the development and progression of ovarian cancer (OC). However, the function of EGLN2 in OC remains unclear. In this study, we observed that EGLN2 is expressed at low levels in OC tissues and is associated with a favorable prognosis in early-stage patients based on data from TCGA and GTEx public databases. Compared with those in normal ovarian epithelial cell lines, EGLN2 mRNA and protein levels were significantly lower in OC cell lines. In vitro functional experiments revealed that EGLN2 overexpression reduced proliferation, increased the intracellular levels of iron ions, reactive oxygen species, lipid peroxidation, and mitochondrial oxidative phosphorylation, and inhibited the Warburg effect. Mechanistically, EGLN2 inhibited the expression of HIF-1α, which binds to the promoter of ceruloplasmin (CP), reducing the proliferation of and inducing ferroptosis in OC cells. A subcutaneous xenograft model in nude mice demonstrated that EGLN2 overexpression inhibited HIF-1α, promoted ferroptosis, and inhibited OC cell growth. In summary, EGLN2 suppressed CP transcription and increased ferroptosis in OC cells. These findings provide new insights into OC development and open avenues for innovative therapies.

Lung cancer is the leading cause of death and the most diagnosed cancer worldwide. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer; 85% of lung cancer patients are diagnosed with NSCLC. Though numerous treatments for lung cancer have been developed, the 5-year survival rate of patients with NSCLC remains low. Therefore, it is urgent to explore novel targets for NSCLC treatment. Growing evidence has revealed that circular RNAs (circRNAs) contribute to NSCLC progression. Besides, the data of circRNA microarray (GSE158695) has found that hsa_circ_0011536 is downregulated in NSCLC tissues. Nevertheless, the role of hsa_circ_0011536 in NSCLC remains unknown. In this study, RNA 6-methyladenosine (m6A) modification was detected by methylated RNA immunoprecipitation, the interaction of RNAs was determined using miRNA pulldown and luciferase reporter assay, while ferroptosis was identified by Cell Counting Kit-8 assay, intracellular iron content, and malondialdehyde level. Our findings demonstrated that hsa_circ_0011536 was downregulated in NSCLC cell lines. Mechanism investigation revealed that m6A modification enhanced the back-splicing of pre-ZMYM4 to increase hsa_circ_0011536 expression in A549 and NCI-H1299 cells. Moreover, hsa-miR-576-5p was the target of hsa_circ_0011536, while transferrin receptor (TFRC) was the downstream target of hsa-miR-576-5p in A549 and NCI-H1299 cells. Furthermore, hsa_circ_0011536 elevated TFRC expression by sponging hsa-miR-576-5p in A549 and NCI-H1299 cells, identified by luciferase reporter assay. In addition, hsa_circ_0011536 induced ferroptosis through hsa-miR-576-5p in A549 and NCI-H1299 cells. Therefore, this study revealed that m6A-induced hsa_circ_0011536 elevated TFRC expression to induce ferroptosis by sponging hsa-miR-576-5p in NSCLC. These results might provide novel therapeutic targets for NSCLC treatment.

Previous studies have shown that Ras-Related Nuclear Protein (RAN), a member of the RAS superfamily, is a small GTPase and an important oncogene in several cancers. However, its role in multiple myeloma (MM) and its potential contribution to drug resistance remain undetermined. Bioinformatics was employed to analyze differentially expressed genes in MM samples. RT-qPCR and western blotting were utilized for protein transcription and expression analysis. The CCK-8 assay was adopted to evaluate cell proliferation, and in vivo animal experiments were conducted to validate the results. The findings reveal that RAN represents one of the most significantly aberrant genes in MM, with its expression significantly elevated in both MM tissues and cells. Genetic manipulation experiments demonstrated that RAN promotes MM cell proliferation by activating the Wnt/PCP pathway. Concurrently, RAN governs the response of MM cells to the anti-cancer drug bortezomib (BTZ). Knockdown of RAN leads to increased sensitivity to BTZ. Mechanistic studies indicate that RAN influences drug response by regulating the activation of the JNK/c-Jun axis, thereby affecting the therapeutic response of MM cells. In summary, the upregulated expression of RAN in MM leads to BTZ resistance via activation of the Wnt/PCP pathway, potentially serving as a novel therapeutic target for MM.

The aim of our research was to evaluate the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for the liver in all patients diagnosed with either primary liver tumor or metastases from other primary malignancies since its initial application at a single institution. A retrospective analysis of the prospective designed registry included 105 patients with 133 liver metastases or primary tumors treated with SBRT from the introduction of the technique in March 2018 until November 2023. The main objectives of the study were to evaluate treatment toxicity, disease control, and survival rates. At a median follow-up of 24 months, a complete response to treatment was achieved in 86.7% of patients. During irradiation, only one patient experienced grade 3 abdominal discomfort, while the other 34.3% of patients experienced only mild acute adverse events (AEs), the majority of which were nausea. After completion of SBRT, 36.2% of patients reported AEs, but only grade 1 and 2 toxicity was observed. The one-, two-, and five-year LC rates were 89.2%, 84.9%, and 84.9%, respectively. DFS rates were 54.7%, 42.9%, and 25.8%; DSS rates were 94.9%, 81.1%, and 46.8%; and OS rates at one, two, and five years were 93.1%, 79.6%, and 43.2%, respectively. In the multivariate analysis, only the number of lesions presented independent prognostic value. In conclusion, SBRT offers effective disease control and survival rates with minimal toxicity, side by side with surgical options as a curative treatment for liver tumors.

Colorectal cancer (CRC) is a malignant tumor originating in the mucosal epithelium of the colon or rectum and is among the most common cancers of the digestive system. Now it is the fourth deadliest cancer in the world. Stimulator of Interferon Genes (STING) is a dimeric transmembrane protein on the endoplasmic reticulum membrane that induces the secretion of type I interferons and pro-inflammatory cytokines and is triggered by the cell membrane DNA of pathogens and hosts. It is widely expressed in immune cells (such as dendritic cells, macrophages) and some tumor cells, and has been shown to play a crucial role in the development of several tumors. However, issues such as the expression of STING in CRC and patient prognosis remain to be further elucidated. We investigated the expression of STING (in CRC tumor cells) and immune markers (CD3, CD4, CD8, CD56, CD163) in 86 CRC patients by tissue microarray using multicolor immunohistochemistry. Subsequently, the effect of STING on the tumor immune microenvironment was further explored. Finally, we analyzed the clinical significance of STING in CRC patients. We found elevated STING expression in tumor cells from CRC patients, which correlated with overall patient survival. High STING levels were associated with suppression of lymph node metastasis and reduction of CD163 tumor-associated macrophages. In contrast, upregulation of STING promoted infiltration of CD3+ T lymphocytes and CD8 lymphocyte subtype in the tumor microenvironment. Our study demonstrated that changes in STING expression in cancer cells in the tumor immune microenvironment have clinical significance and regulatory roles. STING-related functional mechanisms can be considered as therapeutic targets for CRC, which provides a theoretical basis for the subsequent clinical application of STING agonists.