Clinical & Translational Oncology最新文献

Background: The prevalence of lung cancer among individuals afflicted with interstitial pneumonia (IP) stands at approximately 20%. The early detection of lung cancer via chest computed tomography (CT) surveillance proves challenging in IP patients. Our investigation sought to identify a potential biomarker capable of providing early indications of the presence of lung tumors in such patients.

Materials and methods: We examined the attributes of serum tumor markers, imaging characteristics, and histological findings in individuals diagnosed with IP, both with and without concurrent lung cancer.

Results: 106 patients diagnosed with IP were included in the study, comprising 36 individuals with concurrent lung cancer and 70 patients solely diagnosed with IP. Serum concentrations of CEA and CA12-5 were notably elevated in IP patients with lung cancer, compared to those with IP alone. Logistic regression analyses revealed that, in comparison to IP patients within the first quartile of CEA levels, the relative risk of developing lung cancer associated with IP escalated by 4.0-fold, 3.1-fold, 11.0-fold, and 13.3-fold in the second, third, fourth, and fifth quartiles, respectively. Upon controlling for gender and age, statistical significance in risk was observed solely for the fourth and fifth quartiles. Receiver operating characteristic (ROC) curve analysis conducted in patients diagnosed with ILD-CA identified a CEA cutoff point of 6.9 ng/mL, demonstrating sensitivities of 61.1% and specificities of 78.5%. The area under the curve was calculated as 0.7(95% CI: 0.63-0.81).

Conclusion: The serum levels of CEA were notably elevated in IP patients with concurrent lung cancer in contrast to those who were just suffering from IP. The heightened serum CEA levels correlate with an escalated risk of cancer occurrence among IP patients, suggesting that serum CEA levels could potentially serve as an indicative marker for the presence of cancer in IP patients.

Background: Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an emerging pharmacological target in cancer immunotherapy. This study was set out to examine the expression profiles and implications for prognosis and immunotherapy of ERAP1 in CRC.

Methods: Based on bioinformatics and immunohistochemical analysis, we analyzed ERAP1 for potential diagnostic and prognostic significance in CRC. Functional enrichment analysis was conducted to detect the pathways associated with ERAP1, thus determining possible mechanisms. ESTIMATE, TIMER, and CIBESORT probed the links between ERAP1 and tumor-infiltrating immune cells. Lastly, we examined how ERAP1 expression correlated with the sensitivity to immunotherapy.

Results: Tumor tissues had decreased levels of ERAP1 expression relative to normal tissues. Patients whose ERAP1 expression was low suffered a worse chance of survival. Besides, it was shown that ERAP1 expression was associated with the advanced M stage and pathologic stage. Survival analysis revealed that low ERAP1 expression, age, pathologic stage, T stage, and M stage were independent indicators for unfavorable CRC patients' prognoses. The 1-, 3-, and 5-year OS calibration curves all fit well with the ideal model, suggesting that the age-ERAP1-T-stage-M-stage nomogram is a reliable predictor of OS. Additionally, we discovered that ERAP1 expression was associated with immune response and infiltration of various immune cells, such as down-regulated inhibitory immune cells and up-regulated stimulating immune cells. Sensitivity to PD-1 and CTLA4 inhibitors was associated with high ERAP1 levels.

Conclusions: In summary, ERAP1 has potential as a diagnostic and prognostic biological marker, highlighting new insights into the study of CRC and the design of effective therapies.

Purpose: The present consensus statement was developed by the GINECOR working group on behalf of the Spanish Society of Radiation Oncology (SEOR). This document addresses sexual health management in patients with gynaecological cancer after pelvic radiotherapy.

Methods: A modified two-round online Delphi study was conducted, where GINECOR members were surveyed on the diagnosis, treatment, and follow-up of sexual health problems. An expert panel of radiation oncologists, nurses and a gynaecologist participated in the Delphi study to reach a consensus, applying GRADE criteria to establish the level of agreement.

Results: The consensus recommendations cover both diagnosis and treatment, with an emphasis on patient-reported outcome measures (PROMs). They highlight recommendations such as the systematic assessment of genitourinary, gastrointestinal, and sexual symptoms, and the use of several treatments after radiotherapy. Recommendations include pharmacological options like vaginal lubricants and hormone therapy, and mechanical interventions such as vaginal dilators and vibrators. These suggestions stem from both scientific evidence and clinical expertise.

Conclusion: This consensus statement describes a comprehensive, multidisciplinary approach developed to address the sexual needs and enhance the quality of life of patients with gynaecological tumours after pelvic radiotherapy. It offers specific recommendations for managing sexual issues, emphasizing the importance of specialized care and regular assessment. The document underscores the significance of proactive, patient-centered sexual health management in gynaecological cancer patients.

Prognostic assessment is of great significance for individualized treatment and care of cancer patients. Although the TNM staging system is widely used as the primary prognostic classifier for solid tumors in clinical practice, the complexity of tumor occurrence and development requires more personalized probability prediction models than an ordered staging system. By integrating clinical, pathological, and molecular factors into digital models through LASSO and Cox regression, a nomogram could provide more accurate personalized survival estimates, helping clinicians and patients develop more appropriate treatment and care plans. Esophageal adenocarcinoma (EAC) is a common pathological subtype of esophageal cancer with poor prognosis. Here, we screened and comprehensively reviewed the studies on EAC nomograms for prognostic prediction, focusing on performance evaluation and potential prognostic factors affecting survival. By analyzing the strengths and limitations of the existing nomograms, this study aims to provide assistance in constructing high-quality prognostic models for EAC patients.

Background: Primary carcinoma of the ovary (OCs) are responsible for a significant number of deaths related to cancer, and have the highest rate of death related to cancers of the female reproductive organs. Programmed cell death 1 (PD1) protein, acts as an immune checkpoint, and has an important role in the down-regulation of the immune system by preventing the activation of T-cells, which will weaken the autoimmunity and increases self-tolerance. This study aimed at the evaluation of the immunohistochemical (IHC) expression of PD-L1 in various primary surface ovarian epithelial tumours and to test its correlation with different clinicopathological parameters together with the expression of a panel of P53, ER and PR.

Methods: A set of 102 cases of primary ovarian surface epithelial neoplasms (benign, borderline and malignant) were collected to construct Tissue Microarray (TMA) using 3 tissue cores from each case. IHC for PD-L1, p53, PR and ER was performed. The expression of PD-L1 was evaluated in relation to some clinicopathological parameters and to the expression patterns of other markers.

Results: Expression of PD-L1 was detected in about 51% (n = 36) of malignant tumours. The malignant group significantly showed PD-L1 positivity compared to borderline and benign groups. The malignant tumours significantly showed PD-L1 and total p53 positivity in comparison to borderline group. Also, malignant tumours significantly showed higher combined positivity of PD-L1 and either PR or ER compared to borderline and benign lesions. No significant correlation was appreciated between PD-L1 expression and with any of the studied clinicopathological parameters.

Conclusions: This study showed a significant PD-L1 expression in malignant primary surface epithelial tumours. Construction of a panel of IHC markers, including PD-L1, could have a potential value to define patients those would benefit from the addition of immunotherapy to the treatment plan.

Introduction: Recently, genes involved in homologous recombination repair (HRR) pathway have been extensively studied. However, the landscapes of HRR gene mutations remain poorly defined in Chinese high-risk breast cancer (BC) patients. Our study aims to identify the status of germline and somatic HRR gene mutations and their association with clinicopathological features in these patients.

Materials and methods: A total of 100 high-risk BC patients from our institution who underwent paired peripheral blood germline and BC tissues somatic 26 genes next-generation sequencing (NGS) from January 2018 to July 2023 were enrolled for retrospective analysis.

Results: Out of 100 high-risk BC patients, 55 (55%) had at least one germline or somatic mutation in HRR genes. Among them, 22% carried germline pathogenic variants (19 BRCA1/2 and 3 non-BRCA genes), 9% harbored somatic pathogenic mutations (3 BRCA1/2 and 6 non-BRCA genes). Among high-risk factors, family history and early onset BC showed a correlation with HRR gene mutations (p < 0.05). BRCA1 germline and HRR gene somatic mutations showed a correlation with TNBC, but BRCA2 germline mutations were associated with Luminal B/HER2-negative BC (p < 0.05). Patients with HRR gene somatic pathogenic variant more likely had a lympho-vascular invasion and distant metastasis (p < 0.05).

Conclusion: The prevalence of HRR gene germline and somatic mutations were higher in Chinese BC patients with high risk factors. We strongly recommend that these high-risk BC patients receive comprehensive gene mutation testing, especially HRR genes, which are not only related to genetic consultation for BC patients and provide a theoretical basis for necessary prevention and individualized treatment.

Background: The significant expression of PD-L1 in thymic epithelial tumors (TETs) has been confirmed, and immunotherapy and its combination therapy have been effective in TETs. However, there is no present evidence that the expression levels of PD-L1 affects the efficacy of combination therapy. Our study aimed to shed light on this relationship.

Methods: Patients with thymic epithelial tumors (TETs) from multicenter hospitals were retrospectively identified. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) in 22 patients were included. We divided the patients the 22 patients with PD-L1 test into three levels (high expression, low expression and no expression) and analyzed the relationship between the levels of PD-L1 expression and the efficacy of combination therapy.

Results: Combination therapy showed an effective benefit in 22 patients with TETs, the median PFS (mPFS) was 16 months (95% CI: 8.5-23.5) and the median OS (mOS) was 38 months (95% CI: 21.5-54.5). Cox-regressive analysis found whether PD-L1 expression affected the PFS of patients (p = 0.017). Among the patients with PD-L1 expression, the levels of expression were correlated with curative effect (Kruskal-Wallis test, PFS: P = 0.012; OS: P = 0.01), and high expression group was along with better efficacy than low expression (Wilcoxon test, P = 0.01). Moreover, in 17 patients treated with immunotherapy combined with chemotherapy, the expression of PD-L1 was also associated with efficacy (Kruskal-Wallis test, p = 0.021).

Conclusions: PD-L1 expression affects the PFS of patients. High expression of PD-L1 patients with TETs responded better to combination therapy, which could provide a therapeutic option in clinic. Besides, other targeted treatments should be considered.

Purpose: This study aimed to investigate the relationship between the interferon-gamma (IFN-γ) pathway in different tumor microenvironments (TME) and patients' prognosis, as well as the regulatory mechanisms of this pathway in tumor cells.

Methods: Using RNA-seq data from the TCGA database, we analyzed the predictive value of the IFN-γ pathway across various tumors. We employed a univariate Cox regression model to assess the prognostic significance of IFN-γ signaling in different tumor types. Additionally, we analyzed single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database to examine the distribution characteristics of the IFN-γ pathway and explore its regulatory mechanisms, highlighting how IFN-γ influenced cellular interactions within the TME.

Results: Our analysis revealed a significant association between the IFN-γ pathway and adverse prognosis in pan-cancer tissues (P < 0.001). Interestingly, this correlation varied regarding positive and negative regulation across different tumor types. Through a detailed examination of scRNA-seq data, we found that the IFN-γ pathway exerted substantial regulatory effects on stromal and immune cells. In contrast, its expression and regulatory patterns in tumor cells exhibited diversity and heterogeneity. Further analysis indicated that the IFN-γ pathway not only enhanced the immunogenicity of tumor cells but also inhibited their proliferation. Cell-cell interaction analysis confirmed the pivotal role of the IFN-γ pathway within the overall regulatory network. Moreover, we identified HMGB2 (high mobility group box 2) in T cells as a potential key regulator of tumor cell proliferation.

Conclusions: The IFN-γ pathway exhibited a dual function by both suppressing tumor cell proliferation and enhancing their immunogenicity, positioning it as a pivotal target for refined cancer diagnosis and cancer strategies.

Purpose: Currently, there is no consensus regarding whether super-elderly (aged > 80 years) patients are suitable candidates for laparoscopic surgery. This study aimed to analyse the short-term outcomes and oncological prognosis of laparoscopic gastrectomy in super-elderly patients with gastric cancer (GC).

Methods: Following PRISMA and AMSTAR-2 guidelines, we searched the Web of Science, Embase, Cochrane Library, and Pubmed databases from inception until May 2024 and performed a meta-analysis. All published studies exploring the surgical outcomes and oncological prognosis of laparoscopic versus open gastrectomy in super-elderly patients with GC were reviewed. Statistical analyses were performed using RevMan 5.3.

Results: A total of 1,085 studies were retrieved, eight of which were included in the meta-analysis, comprising 807 patients > 80 years of age with GC. The meta-analysis showed that compared with open gastrectomy, patients with GC > 80 years old who underwent laparoscopic gastrectomy had a longer operative time (weighted mean difference [WMD] = 30.48, p < 0.001), less intraoperative blood loss (WMD = -166.96, P < 0.001), shorter postoperative exhaust time (WMD =-0.83, p < 0.001), shorter length of stay (WMD = -0.78, p < 0.001), fewer overall complications (Odds ratio [OR] = 0.54, p = 0.003), higher 5-year overall survival rate (OR = 1.66, p = 0.03) and disease-specific survival rate (OR = 3.23, p < 0.001). Furthermore, laparoscopic gastrectomy did not significantly affect the number of lymph node dissections, the rate of D2 radical gastrectomy, major postoperative complications, or postoperative pneumonia.

Conclusions: Compared to open gastrectomy, patients with GC aged > 80 years who underwent laparoscopic gastrectomy may have better short-term outcomes. Age should not be a contraindication for minimally invasive surgery.