Frontiers in Oncology最新文献

Background: There is little evidence on breast cancer (BC) diagnosed in women with a high genetic risk, before and after their inclusion in a long-term risk management program based on genetic risk assessment. We analyzed clinical outcomes in women enrolled in the Phare Grand Ouest (PGO) program.

Methods: The PGO includes carriers of the BRCA1 and BRCA2 pathogenic variants (PV) and women at high risk without BRCA PV, enrolled in eight cancer genetics units. The study population included all women with incident or prevalent BC, and 1:1 matching by age at first diagnosis was conducted. Multivariable generalized linear and logistic regression models were used to examine the associations between tumor size and cancer stage and the following covariates: age, tumor subtype, pathogenic variant status, prevalent/incident BC status, and healthcare accessibility indicators.

Results: Within the matched cohort, those with incident BC were significantly younger at inclusion, but were of comparable age at the time of first diagnosis. They had smaller tumors, and the odds of advanced-stage disease were approximately 30% lower than those observed in women with prevalent BC (OR = 0.29, p < 0.01). Younger age and a triple-negative phenotype were independently associated with larger tumor size. No significant effect was shown from healthcare accessibility indicators.

Conclusion: The PGO's coordinated, person-centered approach to high genetic risk management was likely associated with earlier-stage BC detection in women with the BRCA PV and women at high risk without BRCA PV. These findings both underscore the enhanced value of person-centered surveillance programs that integrate genetic risk assessment and long-term clinical follow-up, and pave the way for further research in this area.

Background: The third leading cause of death worldwide is colorectal cancer due to a lack of early detection biomarkers and therapeutic small molecules. Advances in systems biology offer a combination of multi-omics and Artificial intelligence to discover the potential biomarkers and targets.

Methods: We used a combination of in silico and in vitro methodologies to identify potential biomarkers and a putative mediator of Embelin in colon cancer treatment. The human colorectal cancer (gene expression profiling by array) datasets were analyzed by using Weighted Gene Co-expression Analysis (WGCNA), and predictive AI models were trained by three algorithms (LASSO, SVM-RFE, RF). All three algorithms predicted COL6A3 as a common hub gene. qRT-PCR was used to analyze the expression level of COL6A3 along with apoptosis markers in HCT116 cell lines (human colorectal cancer) by treating Embelin in a dose-dependent manner.

Results: Trained model predicted COL6A3 as a prominent hub gene across all three ML algorithms with high cross validation accuracy (AUC values: > ~0.90), showing the accuracy of predictions and feature selections of the trained model. Embelin treatment results in the upregulation of pro-apoptotic markers (BAX, CASPASE3) and the downregulation of anti-apoptotic genes (BCL2, PI3KCA). These findings suggest that COL6A3 is a candidate biomarker and a potential mediator of embelin activity.

Conclusion: This study underscores the integration of AI, multi-omics, and in vitro studies for the discovery of candidate biomarkers and mechanistic insights into pathway modulation by Embelin in colorectal cancer. The research successfully identified and validated the role of COL6A3 as a potential biomarker and putative target modulated by Embelin in colon cancer.

Background: Breast cancer is the most common cancer among women. Chinese herbal medicine, which is based on accurate Chinese medicine (CM) syndrome diagnosis, plays a vital role during cancer treatment. This study aimed to validate the established CM syndrome diagnostic criteria for early breast cancer, enhancing their application in clinical settings.

Methods: A multicenter prospective clinical study was conducted to collect epidemiological data on CM syndromes. Two attending doctors from the CM breast department performed syndrome differentiation using established diagnostic criteria and compared it to two clinical experts with associate senior professional titles. Metrics such as sensitivity, specificity, and accuracy were utilized to assess the validity of the diagnostic test.

Results: A total of 641 eligible cases were enrolled from June 2022 to October 2023 from seven hospitals in China. The sensitivity rates for all syndromes ranged from 70.37% to 92.00%, with the highest rate for Spleen and Stomach disharmony in the postoperative stage. Specificity varied from 86.84% to 98.89%, with most criteria exceeding 90%. Overall accuracy of the diagnostic criteria was between 84.25% and 94.45%. Positive predictive values ranged from 72.22% to 98.21%, while negative predictive values spanned from 79.25% to 98.82%, with most syndromes above 80%. The concordance rate for diagnostic criteria ranged from 90.91% to 96.45%, with Kappa values between 0.747 and 0.926.

Conclusions: This study demonstrated that the diagnostic criteria exhibit high reliability, confirming the validity of CM syndrome diagnostic criteria among different treatment stages for early breast cancer and contributing to standardizing clinical practice.

Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. It is characterized by the accumulation of mature monoclonal B lymphocytes. While native kidney infiltration in CLL is relatively common and typically subclinical, involvement of a transplanted kidney is exceedingly rare and may have profound clinical implications.

Case summary: We present the case of a 65-year-old woman with end-stage renal disease secondary to hypertension and diabetes mellitus who underwent kidney transplantation in 2016. Several years later, she was diagnosed with Rai stage I CLL following imaging and histopathologic analysis of axillary lymphadenopathy. Despite an initially indolent course, she developed worsening renal function in 2025. A biopsy of the allograft revealed CLL infiltration consistent with her prior nodal disease. The patient was started on Zanubrutinib, a Bruton tyrosine kinase inhibitor (BTKi), with stabilization of renal function.

Conclusion: This case highlights a rare and clinically significant presentation of CLL involving a renal allograft. As the therapeutic landscape evolves with the advent of BTK inhibitors, prompt recognition and treatment of extranodal CLL involvement may improve outcomes. This case represents only the second reported instance of successful BTKi use for CLL infiltration in a kidney transplant recipient.

Ultra-low rectal cancer (defined as a tumor located within 5 cm from the anal verge) poses unique challenges owing to its distinctive anatomical location, necessitating an optimal balance between oncologic safety and functional preservation. This review focuses on the clinical progress and technological innovations in sphincter-preserving management for ultra-low rectal cancer and is organized within a hierarchical framework encompassing oncologic/anatomical principles, surgical procedures, operative approaches/platforms, specimen-extraction strategies, and multimodal therapy. We first outline plane-based resection principles centered on total mesorectal excision (TME) and key aspects of margin quality control. We then systematically summarize the spectrum of sphincter-preserving procedures, including low/ultra-low anterior resection (LAR/uLAR) and reconstructive options such as coloanal anastomosis (CAA), the transabdominal-transanal approach (TATA), pull-through procedures (Bacon and its modifications), and intersphincteric resection (ISR), with comparisons of indications, oncologic safety, and functional outcomes. Furthermore, we discuss the impact of laparoscopic, robotic, and transanal approaches (e.g., TaTME) on deep pelvic exposure, anatomical precision, and the learning curve, as well as the trade-offs between minimally invasive benefits and safety control associated with specimen-extraction strategies such as NOSE. Finally, we summarize the role of neoadjuvant and total neoadjuvant therapy in facilitating sphincter or organ preservation. Overall, sphincter-preserving treatment for ultra-low rectal cancer should be guided by standardized oncologic principles and tailored combinations of procedures and approaches, with the overarching goal of balancing functional benefit against oncologic safety.

Hepatoid adenocarcinoma (HAC) is an extremely rare and highly malignant tumor with histological features resembling hepatocellular carcinoma but originating from extrahepatic organs, most commonly in the stomach, known as gastric hepatoid adenocarcinoma (GHA). Spontaneous rupture of hepatic metastasis as the initial presentation of GHA is even rarer, posing significant challenges for clinical diagnosis and management. We present a case of a 74-year-old male admitted to the hospital for right upper abdomen pain. Through a combination of imaging, laboratory tests, interventional therapy, and pathological biopsy, the ultimate diagnosis was confirmed as GHA with spontaneous rupture of hepatic metastasis. The patient was transferred for chemotherapy and immunotherapy following transcatheter arterial embolization (TAE). We systematically reviewed relevant literature and summarized the clinical characteristics, diagnostic methods, treatment strategies, and prognosis of GHA with ruptured hepatic metastases. For patients with ruptured liver tumors, a comprehensive assessment of the potential primary site is essential to avoid misdiagnosis. TAE may create opportunities for subsequent curative surgery, chemotherapy, immunotherapy, and targeted therapy, potentially leading to an overall survival benefit. This case report aims to help clinicians gain a deeper understanding of this rare disease, thereby enabling early diagnosis and optimizing treatment strategies.

Objective: To evaluate the predictive value of peripheral blood immune markers for progression to castration-resistant prostate cancer (CRPC) in prostate cancer (PCa) patients undergoing endocrine therapy.

Methods: This retrospective study included 106 PCa patients treated with endocrine therapy between 2021 and 2024. Peripheral blood immune parameters were compared between patients who did and did not experience progression to CRPC (progression and stable groups, respectively). The identified independent predictors of CRPC were then used to construct a nomogram for the identification of high-risk patients for early intervention. Internal validation was performed using the bootstrap method with 1000 resamples. Nomogram performance was evaluated by receiver operating characteristic curve, calibration curve, and decision curve analyses.

Results: Univariate analysis showed significant differences (P < 0.05) in prostate-specific antigen level, Gleason score, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio, systemic immune inflammation index (SII), and pan-immune inflammation value (PIV), CD4+/CD8+ T cell ratio, and T4 stage between the progression and stable groups. Multivariate analysis further identified the PLR, SII, CD4+/CD8+ T cell ratio, and T4 stage as independent risk factors for CRPC development. The developed predictive model demonstrated strong predictive performance (area under the curve =0.934, Hosmer-Lemeshow P>0.05). The c-index for internal validation was 0.914, further confirming the predictive performance of the model. Employing clinically optimized thresholds, survival analysis confirmed that a PLR ≥140, SII ≥520, and CD4+/CD8+ T cell ratio <1.6 could significantly predict the 2-year CRPC risk.

Conclusion: The PLR, SII, CD4+/CD8+ T cell ratio, and T4 tumor stage are independent risk factors for CRPC progression within 2 years of endocrine therapy. The survival prediction model based on these factors offers good predictive efficacy.

Introduction: Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Despite advances in therapy, survival remains poor due to late diagnosis and treatment resistance. Identification of reliable prognostic biomarkers is essential to improve risk stratification and clinical outcomes.

Methods: MRPL23 expression was evaluated as a potential prognostic biomarker in NSCLC using immunohistochemical analysis of tumor specimens from 110 patients and mRNA expression data from The Cancer Genome Atlas (TCGA) cohort. Associations between MRPL23 expression and clinicopathological features, as well as overall survival, were analyzed using survival statistics.

Results: MRPL23 expression was significantly higher in NSCLC tissues than in normal lung tissues (p < 0.0001), with particularly elevated levels observed in squamous cell carcinoma. High MRPL23 protein expression was detected in 57 of 110 cases (51.8%) and was associated with shorter overall survival (median OS 34 vs. 48 months; HR 1.62, 95% CI 1.01-2.58, p = 0.04). These findings were validated in the TCGA cohort, where high MRPL23 mRNA expression correlated with worse overall survival (HR 1.46, 95% CI 1.17-1.83, p < 0.01).

Discussion: MRPL23 overexpression, particularly in lung squamous cell carcinoma, is associated with poor prognosis and may serve as an independent prognostic factor in NSCLC. These results suggest that MRPL23 represents a promising biomarker for improving risk stratification and guiding personalized therapeutic strategies in patients with NSCLC.

The Wnt signaling pathway, a highly conserved molecular cascade, orchestrates critical biological processes including embryonic development, cell differentiation, and proliferation across diverse organisms. Despite the pivotal role that Wnt signaling plays in many diseases, most notably cancer, there are still no FDA-approved, efficacious drugs available that inhibit this pathway. Most Wnt inhibitors target upstream components (e.g., Wnt ligand production and receptors) rather than the most commonly mutated downstream proteins in the pathway. Consequently, there is considerable interest in developing drugs that target the downstream effector, β-catenin. This review examines the challenges in targeting β-catenin, current approaches, and insights into overcoming on-target toxicity associated with cadherin-bound β-catenin.

ROS1 rearrangements define a distinct, targetable subset of non-small cell lung cancer (NSCLC), representing ~2% of non-squamous cases and frequently presenting with metastatic disease and CNS involvement. Multiple ROS1 tyrosine kinase inhibitors (TKIs)-from crizotinib to newer agents such as entrectinib, lorlatinib, repotrectinib, taletrectinib, and the highly selective zidesamtinib-have improved systemic and intracranial outcomes, although resistance remains inevitable and biologically diverse, involving both on-target kinase mutations and off-target mechanisms. This review synthesizes current knowledge on ROS1 biology, diagnostic strategies, therapeutic options, and resistance mechanisms. We outline ROS1 fusion architecture and signaling, highlight partner-specific features, and summarize available diagnostic modalities. In clinical practice, RNA-based next-generation sequencing (NGS), often preceded by immunohistochemistry screening, provides the most sensitive approach for fusion detection and resistance profiling. Given the expanding therapeutic landscape and increasing complexity of treatment sequencing, we adopt a pragmatic, practice-oriented framework. CNS-penetrant next-generation TKIs with activity against common resistance mutations now constitute preferred first-line therapy. Repotrectinib and taletrectinib show strong systemic and intracranial efficacy, including activity against ROS1 G2032R, whereas zidesamtinib offers high selectivity with encouraging early data. Pemetrexed-based chemotherapy remains an effective option, whereas immune checkpoint inhibitors provide limited benefit. At progression, molecular reassessment is essential to guide tailored therapy. Looking ahead, priorities include optimizing sequencing strategies, evaluating perioperative targeted approaches, and incorporating genomic monitoring to anticipate resistance. These advances are reshaping the natural history of ROS1-rearranged NSCLC and supporting a more durable, precision-driven treatment paradigm.