Cancer Management and Research最新文献

Introduction: The evolution of genetic sequencing technologies in Hereditary Breast and Ovarian Cancer (HBOC) from BRCA1/2 analysis to multigene panel sequencing was paralleled with a significant increase in the number of detected variants of uncertain significance (VUS). This trend was found to particularly affect minority populations, such as the underrepresented Middle Eastern population. This study aims at assessing the prevalence and reclassification potential of VUS in a cohort of Levantine patients at risk of HBOC.

Methods: A retrospective chart review of patients at risk of HBOC tested at the American University of Beirut Medical Center between years 2010 and 2019 was conducted. Genetic testing results, as well as epidemiological, clinical and pathology data were extracted for 347 patients. Review and reclassification of VUS were performed according to the latest ACMG/AMP criteria and the ClinGen ENIGMA methodology. Data were analyzed in SPSS v29 using Chi-square and one way ANOVA tests, with p ≤ 0.05 as significant. Significant results were reviewed for confounders using multivariate regression.

Results: 160 genomic alterations classified as VUS were detected. Of those, 32.5% were reclassified, including 4 variants upgraded to pathogenic/likely pathogenic. Non-informative results were present in 40% of participants, with a median of 4 total VUS per patient (mean ACMG pathogenicity score: 3.77). VUS carriers were more likely to have a personal history of breast cancer (72%), specifically triple negative breast cancer (19%).

Conclusion: These findings reveal a high burden of non-informative variants in our population, yet lack of external and functional validation limit the generalizability of our study. Improved genetic diversity in reference datasets and regionally adapted classification strategies are required.

Background: Transfer RNA-derived small RNAs (tsRNAs) are a recently discovered class of non-coding RNAs with aberrant expression in various cancers. Substantial evidence implicates tsRNAs in the initiation and progression of colorectal cancer (CRC). This study aimed to investigate the diagnostic and prognostic potential of a specific tsRNA, tRF5-23-GlyTCC-2, in CRC.

Methods: We identified tRF5-23-GlyTCC-2 via high-throughput RNA sequencing and validated its expression using qRT-PCR. Associations between tRF5-23-GlyTCC-2 expression, clinicopathological features, and patient survival were assessed with Chi-square and Kaplan-Meier analyses. Its diagnostic performance was evaluated by ROC curve analysis. Functional roles in CRC were examined using colony formation assays and xenograft mouse models.

Results: Expression of tRF5-23-GlyTCC-2 was significantly downregulated in CRC tissues (P = 0.0009) and serum (P < 0.0001) compared to controls. It effectively discriminated CRC patients from healthy individuals and those with colorectal polyps, and served as a strong predictor of poor prognosis. Low tRF5-23-GlyTCC-2 levels were correlated with advanced invasion, metastasis (P = 0.0153), and poor prognosis (P = 0.004). ROC analysis demonstrated its superior diagnostic accuracy over traditional biomarkers (AUC = 0.8628), and its combination with CEA further improved the diagnostic performance (AUC = 0.9077). Both in vitro colony formation assays and in vivo xenograft models confirmed its tumor-suppressive function by inhibiting tumor growth and progression.

Conclusion: Serum tRF5-23-GlyTCC-2 exhibits high diagnostic accuracy, and its combination with CEA achieves superior sensitivity (84%), highlighting its potential as a powerful non-invasive biomarker to improve CRC detection and prognosis prediction.

Clear cell ovarian carcinoma is a rare but clinically aggressive subtype of epithelial ovarian cancer characterized by a striking tendency toward hypercoagulability. This narrative review highlights the molecular and clinical underpinnings of CCOC-associated coagulopathy, emphasizing its distinction from other ovarian cancer subtypes. Key drivers include tissue factor overexpression, pro-inflammatory cytokines such as interleukin-6, endothelial dysfunction, and tumor-derived microparticles, all of which converge to activate the coagulation cascade and increase the risk of venous thromboembolism. Comparative data reveal a higher incidence of VTE in CCOC than in serous carcinoma, underscoring the need for histology-specific risk assessment. Current prophylactic strategies rely on standard anticoagulation, but emerging trials targeting coagulation pathways and cytokine signaling show promise for more tailored approaches. Understanding this unique tumor-coagulation interplay is critical for improving early detection, guiding thromboprophylaxis, and informing future therapeutic strategies.

Purpose: Our study aimed to identify the profiles of psychological capital (PsyCap), explore its influencing factors, and examine the association between PsyCap and quality of life (QoL) among breast cancer (BC) patients.

Methods: A total of 229 BC patients completed our survey questionnaire. The questionnaire package included general sociodemographic and clinical information, the Psychological Capital Questionnaire for patients with Cancer (PCQ-C), and the Functional Assessment of Cancer Therapy-Breast (FACT-B). Latent profile analysis was adopted to identify PsyCap profiles. Multivariate logistic regression was used to analyze each profile's sociodemographic and clinical characteristics, and ANOVA was used to explore the relationships between PsyCap profiles and QoL.

Results: Three profiles of PsyCap were identified, including the low PsyCap, moderate PsyCap, and high PsyCap groups, which comprised 23.1, 48.1, and 28.8% of the sample, respectively. K-means clustering further supported the categorization of PsyCap into three distinct profiles. Regression results showed that the low PsyCap group was more likely to be unemployed, a risk factor affecting BC patients' PsyCap. Compared with the low PsyCap group, the moderate PsyCap (Beta=0.209, P=0.002) and high PsyCap (Beta=0.664, P<0.001) groups possessed better QoL.

Conclusion: PsyCap is classifiably heterogeneous among patients with BC, which suggests that healthcare professionals should give full consideration to the impact of unemployment on the PsyCap groups. The PsyCap profiles affected BC patients' QoL, so healthcare professionals can identify BC patients with poor QoL based on their PsyCap and provide them with psychological counseling services and psychological healing groups to help them improve their mental and physical health.

Background: The incidence of early-onset colorectal cancer (EOCRC), defined as diagnosis at age ≤50 years, is rising globally. Despite younger age and presumed clinical fitness, EOCRC often presents at advanced stages and displays distinct biologic and treatment profiles.

Methods: We conducted a retrospective cohort study of patients aged ≤50 years with histologically confirmed colorectal adenocarcinoma treated at a tertiary cancer center in Saudi Arabia from 2015 to 2021. Clinical, pathologic, molecular, and treatment data were extracted. Survival outcomes were analyzed using Kaplan-Meier methods, and prognostic factors were assessed via Cox regression models.

Results: Among 97 patients (mean age 43 ± 5 years; 56% male), 34% presented with metastatic disease and 75% had left-sided or rectal tumors. Obesity was prevalent in 24% of cases. Surgical resection was performed in 79% of patients, of whom 47% received adjuvant chemotherapy. First-line systemic therapy was administered in 39%, but attrition limited progression to subsequent lines. Median overall survival (OS) was 20 months (interquartile range [IQR], 11-30). Progression-free survival (PFS) declined from 8 months in first-line to 4 months in third-line therapy. On multivariable analysis, obesity was independently associated with worse OS (hazard ratio [HR] 6.63, p = 0.035).

Conclusion: Despite favorable performance status, EOCRC frequently presents with advanced disease and limited systemic therapy durability. Obesity emerged as an independent adverse prognostic factor. These findings reinforce EOCRC as a biologically distinct entity, underscoring the need for tailored screening strategies, early intensification of therapy, and molecularly guided care.

Purpose: Cancer and immunosuppressive medications used for its treatment increase the risk for herpes zoster (HZ) among adults. This study described the incidence of HZ and its complications among United States (US) adults with specific solid tumors and hematological malignancies following initiation of immunosuppressive therapy.

Patients and methods: This retrospective cohort study used administrative claims data from October 2015 to December 2022 and included US adults with ≥1 immunosuppressive medication claim, ≥12 months continuous enrollment (baseline) prior to the first immunosuppressive medication claim, a cancer diagnosis, and no HZ diagnosis or vaccination in the baseline period. HZ incidence rates (IRs) were calculated as the number of new HZ cases per 1000 person-years at risk, stratified by cancer type and medication class. The proportions of patients with HZ-related complications such as postherpetic neuralgia, herpes zoster ophthalmicus, disseminated HZ, and HZ-related meningoencephalitis were described. A time-dependent Cox proportional hazards regression estimated adjusted hazard ratios, controlling for patient age, sex, race and ethnicity, comorbidities, prior healthcare utilization, insurance type, region, and baseline immunosuppressive medication use.

Results: The overall IRs of new HZ cases in patients with a solid tumor or a hematological malignancy were 20.9 (95% confidence interval [CI]: 20.33‒21.52) and 31.1 (95% CI: 29.64‒32.52) per 1,000 person-years, respectively. HZ IR was highest in patients with non-Hodgkin lymphoma (35.4, 95% CI: 33.05‒37.77) or chronic lymphocytic leukemia (35.1, 95% CI: 31.24‒39.24). By medication class, the highest HZ IRs were associated with mycophenolic acid, azathioprine, and oral glucocorticoids. In adjusted analyses, patients were more likely to develop HZ during periods of immunosuppressive medication use versus periods without (adjusted hazards ratio [95% CI]: 3.2 [3.01‒3.39] for solid tumor, 3.2 [2.89‒3.57] for hematological malignancy).

Conclusion: HZ incidence among US adults with solid tumors and hematological malignancies following immunosuppressive therapy initiation was high, reinforcing the need to prioritize HZ vaccination in these populations.

SLC7A11 (xCT) is a key subunit of the cysteine/glutamate transporter (system xc ^-), which is crucial for maintaining cellular redox homeostasis (especially glutathione synthesis) and regulating Ferroptosis. It is highly expressed in various malignant tumors and is a key factor leading to treatment resistance, making it an important anti-cancer target. This review systematically summarizes the complex multi-level regulatory network of SLC7A11: at the transcriptional level, key factors form precise regulatory hubs: the KEAP1/NRF2 pathway directly activates SLC7A11 transcription, endowing cancer cells with antioxidant and anti ferroptotic abilities; P53 acts as a core inhibitory factor, and its activity state (activated by STEAP3 iron overload or regulated by Gankyrin/DM2 degradation) directly determines the intensity of inhibition of SLC7A11; ATF4 integrates endoplasmic reticulum stress, oxidative damage, and epigenetic signals (such as SIRT3/KDM3B/KDM4A), and bidirectionally regulates SLC7A11 transcription. Epigenetic regulation involves RNA m6A modification (ALKBH5/FTO reduces stability, METTL3/IGF2BP3 enhances stability) and histone modification (BAP1/PRC1 inhibits through H2Aub). After translation, the stability of SLC7A11 protein is strictly regulated by ubiquitination (SOCS2/HECTD3 promotes degradation, OTUB1/TCF12 inhibits degradation) and palmitoylation (ZDHHC8/DUXAP8 antagonizes degradation). Of particular importance is that non coding RNAs indirectly release their inhibition of SLC7A11 mRNA by acting as "molecular sponges" to adsorb specific miRNAs, profoundly affecting tumor progression and resistance to ferroptosis. This study reveals how cancer cells abnormally upregulate SLC7A11 by hijacking multi-level mechanisms, gaining strong antioxidant/anti ferroptotic abilities, which are the core basis for their survival, proliferation, and resistance to treatment. This study also identified SLC7A11 as a convergence point for multiple key pathways, making it an ideal hub target for intervening in cancer and overcoming drug resistance.

Background: Rising cancer incidence in reproductive-aged individuals, coupled with improved long-term survival, indicates an increasing need for fertility preservation (FP) in this population. However, limited evidence exists on the decision-making of FP from the perspectives of cancer patients in a Chinese context. This qualitative study aimed to examine the patient perceptions of the FP decision and to identify barriers and unmet needs, addressing a significant gap within evolving precision oncology and fertility care contexts.

Methods: Face-to-face, semi-structured interviews were conducted with 12 cancer patients from a tertiary hospital in Hunan Province, China, from March 2024 to June 2024. The interviews were audio-recorded, transcribed verbatim, and analyzed thematically using Colaizzi's seven-step analysis.

Results: Three themes and nine subthemes were identified: insufficient information support (lack of information sources, inappropriate timing of information disclosure, and poor doctor-patient communication); personal and family concerns (impact on cancer treatment, impact on offspring health, marital and reproductive status, financial constraints); ethical dilemmas (conflicts with survival needs, and emotional challenges).

Conclusion: Young cancer patients predominantly aspire to preserve fertility but face multiple decision-making challenges. To address these challenges, healthcare professionals should fully understand the patients' needs, provide accurate and timely information tailored to their needs, and enhance communication skills to facilitate informed decision-making regarding FP, with important implications for clinical practice and public health.

Introduction: The majority of head and neck squamous cell carcinomas (HNSCC) are diagnosed at an advanced stage, often necessitating standard treatments such as surgery or concurrent chemoradiotherapy.

Methods: This was a real-world study conducted between January 2021 and October 2024. The study enrolled 42 previously untreated patients diagnosed with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Patients received induction chemotherapy (IC) with or without immunotherapy followed by radiotherapy at our hospital.

Results: The group receiving immunotherapy with IC (I+IC, N=26) demonstrated an 82.6% objective response rate (ORR) and a 92.3% disease control rate (DCR). In contrast, patients treated with IC (N=16) alone exhibited an ORR of 37.5% and a DCR of 93.8%. With a median follow-up of 28.9 months, the I+IC group showed a 100% 6-month progression-free survival (PFS) and an 88.5% 12-month PFS, with a 92.3% overall survival (OS) rate at 12 months.

Discussion: This real-world study suggests that the addition of immunotherapy to IC holds promise for improving treatment outcomes in locally advanced HNSCC. The findings underscore the need for further research involving a larger patient population to validate these preliminary results.