Oncology Letters最新文献

Melanoma is a highly malignant tumor with a marked propensity for metastasis, and liver metastasis in particular is consistently associated with a poor prognosis. The current study reports the case of a 24-year-old man who presented with multiple systemic metastases 3 years after undergoing radical resection of a cutaneous melanoma. Genetic testing identified a BRAF mutation, which led to the initiation of targeted therapy using dabrafenib in combination with trametinib. After 2 months of treatment, imaging revealed a partial response in the liver metastases. However, by the fourth month, the disease progressed rapidly due to acquired resistance, causing the patient to succumb to liver failure and multiple organ dysfunction. The present case highlights the key need for vigilance, as even young patients with early-stage melanoma remain at risk of rapid disease progression. Therefore, implementing rigorous postoperative patient education and follow-up protocols is key to the early detection of recurrence and timely intervention. Simultaneously, the present case illustrates the challenge of acquired resistance to targeted therapy, underscoring the importance of developing strategies to overcome such resistance to potentially improve patient survival in the future.

DEAH (Asp-Glu-Ala-His) box helicase 15 (DHX15) is a member of the DEAD box RNA helicase family that carries out a key role in innate immunity against viral infections. It is involved in tumorigenesis as a tumor-promoting factor in various types of cancer, but it has also been suggested to act as a tumor suppressor. However, the role of DHX15 in colorectal cancer (CRC) remains largely unknown. In the present study, we examined the role of DHX15 in CRC. Immunostaining of clinical samples from patients with CRC identified DHX15 proteins in the cell nuclei of both tumor and adjacent normal tissues. DHX15 overexpression was revealed to reduce the cell number of various CRC cell lines, as well as the number of Ki67-positive proliferating cells. However, the number of AC3-positive apoptotic cells was comparable between the control and DHX15-overexpressing cells. The possible downstream mechanisms of DHX15 were further examined which revealed that activation of the Wnt/β-catenin and NF-κB signaling pathways were not affected by DHX15 expression. However, DHX15 overexpression resulted in fewer LC3 puncta in HCT116 and DLD1 cells. Taken together, DHX15 may negatively affect CRC cell proliferation, and autophagy may potentially be involved in the downstream mechanism of DHX15.

Breast invasive carcinoma (BRCA) is the most common type of cancer affecting women worldwide. Biomarkers such as estrogen receptor, progesterone receptor and HER2 are currently utilized in clinical practice for breast cancer diagnosis; yet their sensitivity and specificity remain limited. However, Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1), an RNA-binding protein, has been implicated in tumor progression in various cancers, yet its clinical relevance and mechanistic role in BRCA still remain unclear. The present study integrated multi-omics data analysis and experimental validation to address this. G3BP1 mRNA and protein expression levels in BRCA were analyzed using The Cancer Genome Atlas, Tumor Immune Estimation Resource (TIMER) and Clinical Proteomic Tumor Analysis Consortium databases. Kaplan-Meier survival analysis and Cox regression were employed to evaluate the prognostic value of G3BP1. Gene set enrichment analysis (GSEA) was performed to identify associated signaling pathways and immune cell infiltration correlations were assessed using CIBERSORT and TIMER. Additionally, 38 samples of BRCA and adjacent normal tissue were collected for immunohistochemical (IHC) validation and diagnostic efficacy was evaluated using receiver operating characteristic (ROC) curves. G3BP1 was significantly upregulated in BRCA tissues at both mRNA and protein levels (P<0.05). High G3BP1 expression was associated with the advanced cancer lymph node stage (P=0.005) and a poor prognosis [overall survival, disease-free survival (DFS), distant metastasis-free survival and post-progression survival; all P<0.05]. Differential gene analysis identified 67 upregulated and 9 downregulated genes. GSEA revealed G3BP1 enrichment in key pathways such as PI3K/AKT/mTOR signaling and ubiquitin-mediated proteolysis. Immune analysis showed a significant positive association between G3BP1 and M2 macrophage infiltration (P<0.05) and a significant negative association between G3BP1 and CD8⁺ T cells (P<0.05). IHC confirmed higher G3BP1 expression in BRCA compared with normal tissues (P<0.001), with an area under the ROC curve (AUC) of 0.777 and a 5-year DFS prediction AUC of 0.730. The present findings indicate that G3BP1 is a potential independent prognostic biomarker for BRCA. Its upregulation promotes tumor progression by activating the PI3K/AKT/mTOR signaling pathway and modulating the tumor immune microenvironment. These findings provide a theoretical foundation for targeting G3BP1 in BRCA diagnosis and immunotherapy.

Soft tissue sarcomas are therapeutically challenging. Among soft tissue sarcoma subtypes, undifferentiated pleomorphic sarcoma (UPS) exhibits one of the most pronounced disparities between its comparatively higher responsiveness to immunotherapy and its limited responsiveness to conventional cytotoxic chemotherapy. The interplay between immunotherapy and cytotoxic chemotherapy is still largely unknown. Interferon-γ (IFNγ) is a key player in antitumor immunity and contributes to the modulation of the tumor microenvironment, which impacts both immune and cancer cells. The mechanism by which this interplay can affect cancer cell chemosensitivity and immune sensitivity is difficult to predict. The present study aimed to investigate the interplay of IFNγ signaling in the UPS cell line JBT19. It was identified that IFNγ treatment significantly decreased the proliferation of JBT19 cells and increased the surface expression levels of cluster of differentiation (CD)44, CD47, CD95 (Fas), major histocompatibility complex (MHC)-I and programmed death-ligand 1 (PD-L1). In addition, IFNγ strongly upregulated surface expression levels of MHC-II and converted JBT19 cells into docetaxel-resistant cells. The IFNγ-induced changes were sustained but reversible after 3 weeks of cell culture without IFNγ. Regardless of IFNγ treatment, JBT19 cells could elicit and amplify the adaptive immune response in vitro. The in vitro JBT19-reactive lymphocytes effectively eliminated both IFNγ-treated and non-treated JBT19 cells, thus overcoming IFNγ-induced chemoresistance. To the best of our knowledge, the present study demonstrated a dual role of IFNγ towards cancer cell chemoresistance and immunostimulatory potential for the first time. The present study findings may have potential implications for combining immunotherapy with cytotoxic chemotherapy in cancer treatment in the future.

Circular (circ)RNA, a type of non-coding RNA, serves a critical role in several diseases, including cancer. The present study aimed to elucidate the involvement of hsa_circ_0006522 (circEFR3A) in the advancement of breast cancer (BC) and uncover the molecular mechanisms behind its function. Fluorescence in situ hybridization (FISH) was performed on a tissue microarray to assess the expression and intracellular localization of circEFR3A. Kaplan-Meier analysis and Cox proportional hazards model were utilized to evaluate the potential prognostic significance of circEFR3A in relation to the overall survival of patients with BC. The biological function was assessed through gain- and loss-of-function experiments. In addition, dual luciferase reporter assays, RNA immunoprecipitation, FISH and western blotting were performed to identify the interaction between circEFR3A, microRNA (miR)-590-3p and androgen receptors (ARs). Rescue experiments were performed to identify the hypothetical regulatory role of circEFR3A on BC progression in vivo and in vitro. The results of the present study demonstrated that circEFR3A was significantly upregulated in BC tissues and was associated with a poor prognosis in patients. Findings from the Cell Counting Kit-8, colony formation and Transwell assays revealed that increased circEFR3A expression notably promoted BC cell proliferation, invasion and migration, as well as tumor growth in vivo. Mechanistically, circEFR3A was demonstrated to act as a molecular sponge for miR-590-3p in vitro and in vivo, thereby regulating AR expression and functioning as an oncogene. In summary, the findings of the present study indicate that circEFR3A acts as a novel oncogene in BC by sponging miR-590-3p, leading to the upregulation of AR expression and consequently driving BC progression.

Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) presents a notable therapeutic challenge. The efficacy of transarterial chemoembolization (TACE) combined with hepatic arterial infusion chemotherapy (HAIC) and systemic therapy using tyrosine kinase inhibitor and programmed cell death protein 1 inhibitor has not been fully explored. In the present study, the clinical data from 251 patients with HCC and PVTT treated at Harbin Medical University Cancer Hospital (Harbin, China) between January 2021 and December 2022 were retrospectively analyzed. Patients were divided into four groups: TACE-HAIC + lenvatinib + camrelizumab (Group 1; n=16), TACE + lenvatinib + camrelizumab (Group 2; n=90), HAIC + lenvatinib + camrelizumab (Group 3; n=102) and TACE alone (Group 4; n=43). Clinical data included demographics, preoperative indices, tumor characteristics, medical history, performance status, liver function, pre-treatment α-fetoprotein levels and adverse events. Survival outcomes [overall survival (OS) and progression-free survival (PFS)] were analyzed using Kaplan-Meier survival curves. Group 1 exhibited significantly longer OS and PFS times compared with Group 4 (both P<0.05). Adverse events, including fatigue, diarrhea, nausea, vomiting and immune-related pneumonitis, were more frequent in Group 1 (all P<0.001). Group 2 also showed improved OS and PFS times compared with Group 4 (both P<0.05), with notable differences in adverse event profiles. Group 3 demonstrated superior survival outcomes compared with Group 4 (P<0.05), although with a higher incidence of adverse events. No significant differences in OS or PFS times were observed between Groups 1 and 3, or between Groups 2 and 3, indicating comparable efficacy between TACE-HAIC + lenvatinib + camrelizumab and HAIC + lenvatinib + camrelizumab. In conclusion, TACE-HAIC combined with lenvatinib and camrelizumab significantly improved both OS and PFS times in patients with HCC and PVTT compared with TACE alone, despite a higher incidence of adverse events. This combination therapy represents a promising treatment strategy for this patient population, offering enhanced survival benefits.

Urachal carcinoma is a rare and aggressive malignancy with an unknown aetiology and poor prognosis. The present case report described a 31-year-old male patient who initially presented with a 5-day history of haematuria. FDG-PET/CT demonstrated nodules in the anterior wall of the bladder with increased glucose metabolism, which were suggestive of malignancy. A cystoscopic biopsy confirmed the diagnosis of urachal carcinoma. The patient underwent en bloc robot-assisted laparoscopic modified partial cystectomy, along the umbilicus and urachus resection, and pelvic lymph node dissection. The patient recovered within 2 weeks postoperatively, with complete tumour resection confirmed by pathological analysis, which showed negative margins and no recurrence was detected during a 5-month follow-up. The current case highlighted the potential of robot-assisted laparoscopic surgery as an effective treatment option for urachal carcinoma, offering insights for further optimization and broader clinical application, and reviewed the currently available literature.

This study presents a novel case of gastric carcinoma (GC) with diverse histological features and unique molecular alterations. A 62-year-old man with hematemesis was diagnosed with advanced GC and hepatic metastasis. Despite palliative gastrectomy to control bleeding, the patient succumbed within 6 months. Histological examination revealed three distinct tumour components: Gastric adenosquamous carcinoma (GASC), GC with lymphoid stroma (GCLS) and poorly differentiated adenocarcinoma (PDAD). Immunohistochemical staining, next-generation sequencing and Epstein-Barr virus (EBV) in situ hybridisation were performed to characterise the tumour. The GASC component revealed diffuse p40 and p63 immunoreactivity, while the GCLS and PDAD components were negative for both markers. All components harboured a missense mutation in the phosphoinositide-3-kinase regulatory subunit 1 gene and deletions in the ATRX and RNA binding motif protein 10 genes. Additionally, the GCLS component was EBV positive and the PDAD component demonstrated concurrent EBV infection and TP53 inactivation. The present case highlights the importance of thorough molecular and histological evaluation, as distinct molecular alterations and heterogenous EBV status in histologically diverse components may significantly influence patient prognosis and treatment strategies.

Malignant tumors of the smooth muscle of the ureter are extremely rare, with ~13 cases of leiomyosarcoma of the ureter being reported to date. A 59-year-old Caucasian woman presented to 'Umberto I' Hospital (Nocera Inferiore, Italy) with acute abdominal pain, predominantly in the right lumbar fossa. The patient exhibited a functional single kidney, due to left renal atrophy for a long-standing stenosis of the pyelo-ureteric joint. With the exception of this condition and hypertension (under medical therapy), the patient was in excellent clinical condition. Furthermore, the patient was not a smoker. Computed tomography indicated a stricture with a peri-ureteral soft tissue mass of 45×52 mm at the middle third of the ureter at the level of common iliac vessels. Laparoscopic excision with safety margin and a right tension free end-to-end anastomosis between the two stumps of the ureter was performed. The diagnosis of leiomyosarcoma of the right ureter was made by pathological examination. Although leiomyosarcoma is rarely noted in the urinary tract, it should be considered in the differential diagnosis of ureteral stricture disease and retroperitoneal tumors.

Exosomes can be used to mediate the delivery of nucleic acids such as microRNA-125b-5p (miR-125b-5p), a tumor-suppressor in certain types of cancer, into tumor cells. The present study investigated the use of bone mesenchymal stem cells-derived exosome (BMSCs-Exo) delivery of miR-125b-5p in ovarian cancer (OC). BMSCs were transfected with miR-125b-5p mimic, from which exosomes termed Exo-miR-125b-5p mimic were extracted. The expression levels of miR-125b-5p in OC tissue samples, BMSCs, exosomes and SKOV3 cells were quantified using reverse transcription-quantitative PCR. The influence of Exo-miR-125b-5p mimic on the biological functions of OC was evaluated through cell proliferation, invasion, migration and apoptosis assays. The targeting relationship between miR-125b-5p and DEAD-box helicase 5 (DDX5) was verified, and the expression levels of DDX5 in OC samples and SKOV3 cells were quantified using western blotting. miR-125b-5p was downregulated in tumor tissue samples from patients with OC. BMSCs-Exo reduced the malignant properties of SKOV3 cells in vitro, and these effects were be advanced by miR-125b-5p upregulation. miR-125b-5p targeted and inhibited DDX5 expression. DDX5 overexpression inhibited Exo-miR-125b-5p-induced suppression of OC development. Overall, this study highlights that BMSCs-Exo-encapsulated miR-125b-5p inhibited OC progression via DDX5 downregulation, providing insight into the molecular mechanisms underlying OC.