Cancer Investigation最新文献

Recently some serologic parameters emerged as potential prognostic factors of triple-negative breast cancer (TNBC). We aimed to establish the most relevant factors and select optimal cutoff points for prospective investigations. Data from 137 TNBC patients treated with neoadjuvant chemotherapy were analyzed. Beyond pathological factors, white blood cell, neutrophil (NE), lymphocyte (LY) and platelet counts, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII) were investigated at baseline and before the third cycle. In univariate analysis, most parameters at baseline (NE1, LY1, NLR1, PLR1, SII1), in multivariate analysis NLR1 and pathological stage showed significant association with survival.

The BK polyomavirus (BKPyV), a ubiquitous human pathogen, has garnered significant attention for its potential oncogenic role, particularly in immunocompromised populations such as transplant recipients. This review synthesizes current evidence on the molecular mechanisms underlying BKPyV-associated carcinogenesis, with a focus on the viral Large T antigen (LT-Ag). LT-Ag drives oncogenic transformation primarily by inactivating tumor suppressor proteins p53 and pRb, disrupting cell cycle regulation, and inhibiting apoptosis. Additionally, it dysregulates critical signaling pathways, including Wnt/β-catenin, PI3K/Akt/mTOR, Ras/Raf/MAPK, and STAT-3, which collectively promote uncontrolled proliferation, survival, and genomic instability. A hallmark of BKPyV's oncogenicity is its capacity to integrate into the host genome, often near tumor suppressor loci, further amplifying chromosomal damage. Clinically, BKPyV has been implicated in urothelial carcinoma, renal cell carcinoma, and prostate cancer, with viral DNA and LT-Ag detected in 20-50% of tumor specimens from kidney transplant recipients (KTRs). However, epidemiological data remain contentious, as studies in immunocompetent cohorts report inconsistent associations, and viral presence in non-neoplastic tissues complicates causal interpretations. This duality BKPyV as both a latent commensal and a potential oncogenic driver underscores the need for nuanced investigation into host-virus interactions, particularly in the context of immunosuppression. Emerging diagnostic approaches, such as next-generation sequencing to map viral integration sites, and therapeutic strategies targeting LT-Ag-mediated pathways hold promise for early detection and intervention. By bridging molecular insights with clinical observations, this review advocates for longitudinal studies to clarify BKPyV's role in carcinogenesis and to refine management protocols for high-risk populations, ultimately mitigating the burden of virus-associated malignancies.

CHEK2 is a moderate-penetrance tumor suppressor gene primarily linked to hereditary breast cancer, yet growing evidence implicates it in a wider tumor spectrum. Data from underrepresented populations, such as Türkiye, remains limited. We retrospectively analyzed 895 individuals referred for hereditary cancer evaluation between 2019 and 2025 who underwent multigene panel testing. Germline CHEK2 variants were identified using the Hereditary Cancer Solution Kit (Sophia Genetics) and classified per ACMG guidelines. Clinical, tumor, and histopathological data were reviewed. Twenty-four carriers (83.3% female) were detected: 45.8% harbored pathogenic, 41.6% likely pathogenic, and 12.5% variant of uncertain significance. Breast cancer was the most frequent (66.6%), followed by bladder cancer (8.3%), with isolated cases of ovarian, cervical, lung, papillary thyroid cancers, parathyroid adenoma, and thymoma. Missense variants predominated (75%), clustering in the FHA (66.6%) and kinase (33.4%) domains. Recurrent c.470T > C and c.1427C > T variants comprised 41.6% of all cases. Our findings highlight variant- and sex-specific patterns and underscore the relevance of population-based data in refining cancer risk assessment and management of CHEK2 carriers.

Esophageal cancer remains a leading cause of cancer-related morbidity and mortality worldwide, with East and South Asia bearing a disproportionate burden. Despite global declines in age-standardized rates, these regions continue to face challenges due to sociodemographic and behavioral factors. Using Global Burden of Disease 2021 data, we analyzed trends in prevalence, incidence, mortality, and Disability-Adjusted Life Years (DALYs) from 1990 to 2021, emphasizing gender disparities and risk factor contributions. East Asia showed notable progress, with China reporting a 33.96% decrease in age-standardized incidence rate (ASIR) and a 45.78% decline in age-standardized mortality rate (ASMR). Korea also demonstrated improvements, whereas Taiwan recorded only a 4.69% reduction in ASIR but a striking 141.62% rise in ASMR. In South Asia, Bangladesh achieved a 32.74% fall in ASIR and Nepal a 19.01% decline, while Pakistan reported increases in both ASIR (+8.47%) and ASMR (+8.52%). Gender analyses revealed higher ASIR and ASMR among men, except in Pakistan where chewing tobacco drove higher female rates. Tobacco use accounted for 53.1% of the burden in South Asia and 55.2% in East Asia, dominated by smoking in East Asia and chewing tobacco in South Asia. These findings highlight the need for gender-sensitive interventions, stronger tobacco control, dietary improvement, and enhanced screening.

As use of real-world evidence (RWE) in oncology continues to increase, guidance is needed to ensure the patient voice is captured when generating RWE. This paper proposes a practical methodological framework for patient-centered RWE (PCRWE) throughout oncology product development. The need for a novel framework was first established by a review of existing literature and RWE guidelines. This review indicated an unmet need for a clear definition of PCRWE and a framework to guide PCRWE research in oncology. We define PCRWE as RWE that incorporates patient-centered objectives, provides insights into patient-relevant questions, and may lead to assessments of the usage, benefits, or risks of a medical treatment reflecting the patient perspective. The review's findings were used to create a preliminary PCRWE framework, which was finalized following interviews with RWE stakeholders and oncologists. The final PCRWE framework, which is grounded in the existing regulatory and scientific landscape, is an interactive visual tool for generating, implementing, and disseminating PCRWE in oncology. It accommodates various levels of expertise among users and supports the alignment of terminology to describe PCRWE. The framework will enable stakeholders to identify unmet needs from the patient perspective and to more effectively demonstrate the value of new oncology products.

Introduction: Metastatic melanoma carries a poor prognosis. Immune checkpoint inhibitors (ICIs) have improved outcomes, but responses remain variable, highlighting the need for simple prognostic biomarkers. Inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lactate dehydrogenase (LDH) reflect tumour burden and inflammation, though their clinical utility is unstandardised.

Methods: We retrospectively analysed 103 metastatic melanoma patients treated with anti-PD-1 monotherapy at two centres in Western Australia (2014-2020). Baseline NLR, PLR, and LDH were assessed within 30 days pre-treatment. Outcomes included clinical benefit, progression-free survival (PFS), and overall survival (OS).

Results: Poor ECOG performance status (PS ≥2) (RR 2.39, 95% CI 1.48-3.86) and elevated LDH (≥250 U/L) (RR 1.68, 95% CI 1.21-2.31) were associated with no clinical benefit (p < 0.001). NLR ≥5 predicted significantly worse OS (9.1 vs 28.2 months; HR 8.54, 95% CI 2.58-28.32; p < 0.001). Elevated LDH predicted shorter OS (6.0 vs 50.3 months; HR 3.68, 95% CI 1.65-8.21; p = 0.002) and PFS (19.0 months vs not reached; HR 2.51, 95% CI 1.37-4.72; p = 0.004).

Conclusion: ECOG PS ≥2 and elevated NLR were associated with no clinical benefit, while elevated NLR and LDH independently predicted poorer survival. These markers may serve as practical prognostic tools in metastatic melanoma treated with ICIs.

Background: Parathyroid carcinoma, a rare endocrine malignancy, is a significant diagnostic and therapeutic challenge due to its overlapping features with benign parathyroid diseases and high recurrence rates.

Objectives: The study assessed the demographic, biochemical, surgical, and histopathological characteristics of parathyroid carcinoma patients at a high-volume endocrine surgery center and identified clinical predictors of postoperative outcomes.

Methods: A retrospective cohort study was conducted on 8 patients who underwent surgery for histopathologically confirmed PC between January 2018 and December 2023. Data on demographics, biochemical markers, imaging, operative approach, and postoperative outcomes were analyzed. Spearman's rank correlation and multivariate linear regression were applied to identify key predictors of postoperative parathyroid hormone levels.

Results: The cohort comprised 4 females and 4 males with a mean age of 57.8 ± 7.1 years (range: 50-71 years). The mean preoperative serum PTH and calcium levels were: 688.96 ± 196.17 pg/mL and 12.90 ± 1.38 mg/dL, respectively. Distant metastasis was observed in 25% of cases, and lymph node involvement in 12.5%. Multivariate analysis revealed that male sex, preoperative calcium, intraoperative PTH, presence of comorbidities, and adjuvant therapies significantly influenced postoperative PTH levels (p < 0.05). Imaging was universally performed but lacked specificity for malignancy.

Conclusion: Parathyroid carcinoma presents a diagnostic challenge due to its similarity to benign disease. Preoperative evaluation, comprehensive histopathology, and en bloc surgical resection are crucial for curative treatment.

The primary objective of this review is to provide a comprehensive analysis of salivary biomarkers in the context of oral cancer, with a particular focus on oral squamous cell carcinoma. Oral cancer is a serious global health concern, ranking as the sixth most common cancer worldwide with over 300,000 new cases annually, and as the third most prevalent cancer in India. Its high morbidity and mortality are largely attributed to late-stage diagnosis and limited access to timely care. The current diagnostic gold standard, tissue biopsy, is invasive, costly, and unsuitable for population-level screening, creating a need for alternative approaches. This review critically evaluates recent advancements in diagnostic methodologies, emphasizing saliva as a noninvasive diagnostic medium. It examines relevant clinical case studies to demonstrate the diagnostic efficacy of salivary biomarkers and explores key etiological factors associated with oral cancer. Public health strategies initiated by governmental agencies to improve early detection, screening, and awareness are also discussed. The findings highlight that salivary biomarkers hold significant promise for early detection and cancer diagnostics. Conclusions emphasize the translational gaps that persist in this area, underscoring the need for further research to enable their integration into diagnostic protocols, screening programs, and public health initiatives.

Cervical cancer is the fourth most frequent cancer in females, with a high mortality rate globally. Persistent infection with high-risk, oncogenic human papillomavirus (HPV) types is a critical etiologic factor in the progression of the disease. Unfortunately, cervical cancer often remains undiagnosed until advanced stages, hence limiting treatment effectiveness. Therefore, identifying precise and significant biomarkers is crucial. High-throughput sequencing technologies have revolutionized targeted cancer therapy research by generating extensive data for analysis. This study employed bioinformatics and machine learning (ML) approaches to identify dysregulated genes with significant diagnostic value in cervical cancer, utilizing transcriptomics datasets. Seven potential diagnostic biomarker genes (APOD, SPARCL1, AR, MCM2, NUSAP1, PLK1, and STIL) were validated by a real-time polymerase chain reaction (RT-PCR) experiment. The ML models were developed using significantly differentially expressed genes (DEGs) involved in important pathways for cervical cancer. ML prediction models are available at https://github.com/PGlab-NIPER/CC_Pred.

Mammary Paget's disease (MPD) is a rare breast malignancy often associated with ductal carcinoma in situ or invasive carcinoma. However, its diagnosis remains challenging owing to the subtlety or absence of findings on conventional imaging. In this study, we retrospectively analyzed 12 Japanese patients with MPD. All patients showed uniform overexpression of the human epidermal growth factor receptor 2 (HER2; immunohistochemistry score = 3+), with 92% exhibiting associated ductal carcinoma in situ. Magnetic resonance imaging (MRI) revealed skin and nipple enhancement in 78% of patients, along with non-mass enhancement and nipple thickening that correlated with the pathological findings. Moreover, Ki-67 proliferation index was high in most cases (median, 67%), indicating the presence of biologically active tumors. No recurrence or death was observed during the median follow-up period of 96 months. Overall, our findings suggest that HER2-positive MPD exhibits aggressive biological behaviors despite a subtle clinical presentation and highlight the importance of MRI in its detection. Furthermore, integration of imaging with pathological and molecular marker assessment is essential for accurate MPD diagnosis and treatment. This study on a Japanese cohort provides valuable insights and highlights the diagnostic utility of MRI for MPD, especially HER2-driven MPD.