Technology in Cancer Research & Treatment最新文献

IntroductionRenal cancer, particularly Kidney Renal Clear Cell Carcinoma (KIRC), remains a major clinical challenge due to its aggressive nature and poor prognosis. Identifying reliable biomarkers for tumor progression and survival is critical for improving patient outcomes. This study aimed to investigate the role of Centromere Protein F (CENPF) as a potential prognostic biomarker for renal cancer.MethodData from the TCGA database, including Kidney Chromophobe (KICH), Kidney Renal Papillary Cell Carcinoma (KIRP), and KIRC, were analyzed to identify differentially expressed genes. Molecular Complex Detection (MCODE) was used to identify significant gene modules among upregulated genes, and univariate Cox regression analyses assessed the prognostic value of hub genes. Retrospective qPCR was conducted on tissue and plasma samples from KIRC patients to validate findings. Single-cell sequencing data from the GSE159115 dataset were analyzed, and the CIBERSORT algorithm was applied to evaluate the composition of tumor immune infiltrating cells (TIICs).ResultsCENPF was identified as a hub gene significantly upregulated in renal cancer subtypes, with overexpression linked to worse survival outcomes in KIRC patients. Retrospective qPCR confirmed high CENPF expression was associated with poorer prognosis. Single-cell sequencing revealed that CENPF is predominantly expressed in T-cell clusters. TIIC analysis showed a negative correlation between CENPF and resting mast cells, but positive correlations with follicular helper T-cells and memory-activated CD4T-cells. Prognostic analysis indicated that high follicular helper T-cell expression predicted poorer survival, while high plasma cell expression correlated with better outcomes.ConclusionCENPF plays a critical role in tumor progression and the modulation of the tumor immune microenvironment in KIRC. These findings suggest that CENPF could serve as a valuable prognostic biomarker and potential target for therapeutic intervention in renal cancer.

Background: The prognostic value of the Geriatric 8 (G8) screening score in metastatic renal cell carcinoma (mRCC) patients receiving first-line immunotherapy remains unclear. This study aimed to evaluate the prognostic role of G8 within the context of the Meet-URO classification in mRCC patients treated with first-line ipilimumab-nivolumab.

Methods: This retrospective multicentre study analysed 106 mRCC patients treated with first-line ipilimumab-nivolumab. G8 and Meet-URO scores were calculated before treatment initiation. Primary endpoint was overall survival (OS), defined as duration from first administration of Nivolumab to death. OS was analysed in relation to age groups, G8 scores, and Meet-URO score categories, with data censored for patients still alive at the last follow-up. The secondary endpoint, progression-free survival (PFS), was measured from initiating Nivolumab to the earliest instance of disease progression or death. OS and PFS were assessed using Kaplan-Meier methods and Cox regression analyses. The reporting of this study conforms to the REMARK guidelines.

Results: Patients with G8 > 14 had more favorable IMDC and Meet-URO risk classifications and lower neutrophil-to-lymphocyte ratios. While PFS did not differ significantly between G8 ≤ 14 and >14 groups (1-year 29.3% vs 46.2%, p = 0.2), OS was significantly longer in G8 > 14 group (1-year 76.1% vs 58.6%, p = 0.006). In multivariable analysis, G8 ≤ 14 was independently associated with worse OS (HR 2.36, 95% CI 1.06-5.08, p = 0.03) but not PFS. The Meet-URO score was prognostic for both PFS and OS. In patients ≥70 years, G8 lost its prognostic value, while Meet-URO remained prognostic for OS.

Conclusions: The G8 score is an independent prognostic factor for OS but not PFS in mRCC patients receiving first-line ipilimumab-nivolumab. The Meet-URO score shows consistent prognostic ability for PFS and OS across age groups. These findings suggest that while G8 may be useful for individual patient-level OS prediction, the Meet-URO score may be superior for guiding treatment decisions in clinical practice.

IntroductionUterine sarcoma (US) is an extremely rare and aggressive gynecologic malignancy with a poor overall survival (OS). The efficient prognostic biomarker is currently lacking.MethodsUtilizing a Sweden microarray dataset from the Gene Expression Omnibus (GEO) (GSE119043, n = 50) and a clinical cohort (n = 31) retrospectively collected from Suining Central Hospital, we analyzed β-catenin expression profiles and corresponding clinicopathological characteristics. Immunohistochemistry (IHC) was used to assess β-catenin expression level. Survival analysis was used to assess the relationship between β-catenin expression and prognosis. Gene set enrichment analysis (GSEA) was performed to characterize the specific pathways involved in β-catenin expression.ResultsImmunohistochemistry indicated that β-catenin expression was significantly upregulated in US group compared to both the normal uterine smooth muscle (UNSM) and uterine leiomyoma (ULM) groups (P < .01). IHC also exhibited a significant difference in β-catenin expression levels in four pathological subtypes. Leiomyosarcoma (LMS) and high-grade endometrial stromal sarcoma (HG-ESS) suggested higher levels of β-catenin expression compared with adenosarcoma (AS) or low-grade endometrial stromal sarcoma (LG-ESS), but no statistically significant difference was found in box plot (P > .05). GSEA indicated that transcriptional dysregulation in cancer, Wnt, AMPK, MAPK, PI3K, p53, Ras, and TNF signaling pathway were positively enriched in β-catenin high-expression group. Though survival analysis showed that β-catenin expression level was not associated with survival, low-β-catenin expression group showed a longer median OS compared to high expression group (56.17 months VS 9.60 months) in Sweden microarray dataset. Similar results were also observed for progression-free survival (PFS) in clinical cohort (not reached VS 45.97 months in high-expression group). Tumor type, lymphadenectomy, family history of malignancy and tumor recurrence remained significant predictors of OS, while only tumor type, stage and tumor recurrence had prognostic significance for PFS. Age, tumor size, menopausal status, CA125, adjuvant chemotherapy, and adjuvant radiotherapy, were not associated with survival (P > .05).Conclusionβ-catenin was highly expressed in uterine sarcoma and may be promising as a novel potential biomarker for diagnosis and prognosis.

Stereotactic radiotherapy (SRT) has become integral to modern oncology, offering the ability to deliver ablative doses while minimizing damage to surrounding normal tissues. Recent advancements in imaging integration, treatment planning, and dose delivery have expanded their clinical applications across various tumor types. However, challenges such as toxicity in anatomically critical regions, optimal margin determination, and the lack of standardized protocols persist. This review explores key issues in contemporary practice and highlights emerging clinical evidence across lung, liver, prostate, brain, and oligometastatic diseases. Further refinement in patient selection and treatment strategies is essential to maximize therapeutic efficacy and ensure safe implementation in broader clinical settings.

Osteosarcoma (OS) is the most common primary bone malignancy, with lung metastasis being the leading cause of mortality. The metastatic process is driven by complex biological mechanisms, including tumor cell-specific adaptations of growth pathways, immune modulation within the tumor microenvironment, and reactivation of metastatic cells from dormancy. This scoping review captures overlooked and under researched pathways, supporting mainstream therapeutic targets while shedding light on novel ones, reinforcing and revising conclusions drawn in previous literature, and guiding future research. MEDLINE, Embase, and Cochrane CENTRAL were searched with a publication date limit from 2019 onwards using relevant MeSH terms combined with Boolean operators, truncations, and keyword searches. The search culminated in 43 reports, including 30 in vivo, 8 in vitro, and 5 observational studies. This study conforms to the PRISMA-ScR guidelines. Tumor cell adaptations, including epithelial-mesenchymal transition (EMT) and enhanced migratory and proliferative signaling via JAK/STAT and TGF-β pathways, are critical drivers of OS lung metastasis. Manipulated upstream ligand-driven signaling promotes transcriptional changes that increase cell cycle proteins and mesenchymal markers, conferring chemoresistance and advancing OS cells toward a metastatic state. The tumor microenvironment also plays a key role; interactions between OS cell-derived cytokines and tumor-infiltrating immune cells lead to tumor associated macrophages and neutrophils (TAMs/TANs), which help establish a pre-metastatic niche and provoke immune remodeling. However, the impact of TAMs on OS survival remains ambiguous due to their dual pro- and anti-tumor roles. Lung-induced dormancy links tumor intrinsic and immune-driven mechanisms, allowing tumor cells to evade immunity or pause progression. Inflammatory pathways and immune activation can reverse dormancy, promoting further OS dissemination. The reviewed evidence supports targeting intracellular signaling and immune pathways to mitigate OS metastasis. The paucity of longitudinal data on lung dormancy warrants caution, emphasizing integrated approaches and better controlled studies with focus on combinatorial therapies for more conclusive outcomes.

IntroductionTo investigate the efficacy of a knowledge-based planning (KBP) model in optimizing dose distribution, and identify the inter-institutional variation in radiotherapy of recurrent nasopharyngeal carcinoma (rNPC).MethodsA total of 70 rNPC patients treated with intensity-modulated radiotherapy (IMRT) were recruited to build a KBP model. Following model refinement, 36 patients were retrospectively enrolled for dosimetric comparison between manually optimized and KBP-generated plans. Ten experienced physicists from six different institutions were engaged to independently design manual plan for a representative case, to assess inter-institutional variations, and differences between KBP and manual plans.ResultsThe refined KBP model provided significant reduced dose in brainstem D_1cc (the dose received by the "hottest"1 cm³ volume, 41.14 ± 8.51 Gy vs 38.48 ± 8.60 Gy, P < 0.001) and spinal cord D_1cc (17.48 ± 9.38Gy vs 12.23 ± 6.56Gy, P < 0.001). In addition, The mean dose (D_mean) of brainstem, spinal cord, mandible, parotid, temporomandibular joint and inner ear were statistically decreased (P < 0.05). In validation cohort, KBP model eliminated the hotspot (0.57 ± 0.01% vs 0.00 ± 0.00%, P < 0.001), improved target homogeneity (HI: 0.06 ± 0.00 vs 0.08 ± 0.00, P < 0.001), and performed superior to the manual plans in sparing organs. While all institutions achieved comparable target coverage, manual plans exhibited substantial variability in sparing brainstem. KBP implementation reduced inter-institutional dose disparities for brainstem (46.30 ± 10.08 Gy vs 41.80 ± 5.80 Gy, P = 0.041) and spinal cord (26.08 ± 7.06 Gy vs 18.19 ± 1.98 Gy, P = 0.002). Additionally, planning efficiency increased by 48.7% (39 vs 76 min).ConclusionsThis KBP framework optimized rNPC reirradiation from three dimensions: 1) Enhanced OARs' protection; 2) Improved target homogeneity; 3) Improved the multi-institutional consistency and efficiency of planning. These advancements established a clinically actionable paradigm for precision reirradiation.

BackgroundEndometrial carcinoma (EC) represents a unique clinical challenge. Fertility-sparing treatments rely on achieving complete response (CR) through progesterone-based therapy. We sought to investigate the prognostic value of molecular subtyping and immunohistochemical (IHC) markers in predicting three-month treatment outcomes and recurrence in EC patients undergoing fertility-sparing therapy.MethodsA retrospective cohort of 68 patients diagnosed with early-stage EC received hysteroscopic surgery and conservative treatment whose paraffin-embedded tissue blocks preserved in our hospital between Jan. 2010 and Oct. 2022 was evaluated. Molecular subtyping based on TCGA classification identified low copy-number (CNL), microsatellite instability-high (MSI-H), and copy-number high (CNH) subtypes. IHC markers, including PTEN, PIK3CA, β-catenin, ARID1A, estrogen receptor (ER), and progesterone receptor (PR) were analyzed for their association with CR and recurrence. Transcriptome sequencing gene chips were used to study patients who achieved or did not achieve CR after three months, those who experienced recurrence within one year, and those who did not recur within two years. Differential genes were then mapped to KEGG pathways to explore the underlying mechanisms of progesterone therapy efficacy.ResultsAmong the 68 patients classified through TCGA molecular typing, 65 cases (95.6%) were CNL subtype, two (2.9%) were MSI-H subtype, and one (1.5%) was CNH subtype. Following a three-month treatment, the CR rate for the CNL subtype was 75.4% (49/65), the MSI-H subtype was 50.0% (1/2), and the CNH subtype was 0% (0/1). In CNL subtype endometrial carcinoma, individuals with high PTEN and PR expression were more likely to achieve CR after three months (P < .05). Conversely, those with elevated CA199 levels and increased PIK3CA expression were more prone to recurrence after CR.ConclusionMSI-H and p53-mutant subtypes of endometrial carcinoma are not suitable for fertility preservation therapy. PTEN/PI3K-AKT-mTOR pathway activation contributes to reduced progesterone sensitivity, underscoring the need for targeted therapeutic strategies to improve patient outcomes.

IntroductionThe utility and application of endocervical curettage (ECC) during colposcopy remain controversial. This study optimized ECC application for primary human papillomavirus (HPV) screening in patients with high-risk (HR)-HPV.MethodsThis retrospective study included patients with HR-HPV, who underwent subsequent cervical biopsy and ECC from January 1, 2014, to December 31, 2020. Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). The prediction model was presented as a nomogram and evaluated for discrimination and calibration.ResultsThe additional detection rate of cervical intraepithelial neoplasia 2 + lesions with ECC was 2.0% (77/3887) in patients with HR-HPV. In multivariate risk factor analysis, HPV 16 infection presented a high risk of positive ECC, followed by HPV 33, HPV 58, and HPV 31. Irrespective of the abnormal cytopathological results, positive ECC was significantly increased (all P < .001). Females with acetowhite changes on colposcopy, transformation zone (TZ) type II, TZ type III, colposcopic impression of high-grade squamous intraepithelial lesion, or cancer were at a high risk of positive ECC. The final prediction model included significant variables from risk factor analysis, and had excellent calibration and classification capabilities, with an area under the receiver operating curve of 0.902 (95% CI, 0.881-0.922). Additionally, calibration analysis suggested consistency.ConclusionAs the additional detection value of ECC is limited. A satisfactory prediction model was designed to optimize ECC application in patients with HR-HPV infection.

Low temperature plasma (LTP), as an emerging cancer treatment technology, has shown significant therapeutic potential due to its unique physical and chemical properties and biological effects. This article reviews the basic characteristics of LTP and its multiple mechanisms of application in tumor treatment. LTP can induce various cell death modes, including apoptosis, pyroptosis, and autophagy, through its unique chemical and physical properties. Additionally, studies have demonstrated that the combination of LTP with traditional chemotherapy drugs (such as cisplatin and paclitaxel) can enhance the anti-tumor efficacy of the drugs while reducing drug resistance. The combined application of LTP and nanomaterials also shows promising prospects. However, LTP still faces some challenges and limitations in medical applications. Future research needs to further explore the specific applications of LTP in different tumor types, optimize treatment plans, and develop more portable and efficient LTP devices to promote its application in clinical treatment.