Journal of Cancer Research and Clinical Oncology最新文献

Purpose: The HUNT Lung Cancer Model (HUNT LCM) predicts individualized 6-year lung cancer (LC) risk among individuals who ever smoked cigarettes with high precision based on eight clinical variables. Can the performance be improved by adding genetic information?

Methods: A polygenic model was developed in the prospective Norwegian HUNT2 study with clinical and genotype data of individuals who ever smoked cigarettes (n = 30749, median follow up 15.26 years) where 160 LC were diagnosed within six years. It included the variables of the original HUNT LCM plus 22 single nucleotide polymorphisms (SNPs) highly associated with LC. External validation was performed in the prospective Norwegian Tromsø Study (n = 2663).

Results: The novel HUNT Lung-SNP model significantly improved risk ranking of individuals over the HUNT LCM in both HUNT2 (p < 0.001) and Tromsø (p < 0.05) cohorts. Furthermore, detection rate (number of participants selected to detect one LC case) was significantly better for the HUNT Lung-SNP vs. HUNT LCM in both cohorts (42 vs. 48, p = 0.003 and 11 vs. 14, p = 0.025, respectively) as well as versus the NLST, NELSON and 2021 USPSTF criteria. The area under the receiver operating characteristic curve (AUC) was higher for the HUNT Lung-SNP in both cohorts, but significant only in HUNT2 (AUC 0.875 vs. 0.844, p < 0.001). However, the integrated discrimination improvement index (IDI) indicates a significant improvement of LC risk stratification by the HUNT Lung-SNP in both cohorts (IDI 0.019, p < 0.001 (HUNT2) and 0.013, p < 0.001 (Tromsø)).

Conclusion: The HUNT Lung-SNP model could have a clinical impact on LC screening and has the potential to replace the HUNT LCM as well as the NLST, NELSON and 2021 USPSTF criteria in a screening setting. However, the model should be further validated in other populations and evaluated in a prospective trial setting.

Background: Cancer-associated fibroblasts (CAFs) play a crucial role in the progression of colorectal cancer (CRC). However, the impact of CAF subpopulation trajectory differentiation on CRC remains unclear.

Methods: In this study, we first explored the trajectory differences of CAFs subpopulations using bulk and integrated single-cell sequencing data, and then performed consensus clustering of CRC samples based on the trajectory differential genes of CAFs subpopulations. Subsequently, we analyzed the heterogeneity of CRC subtypes using bioinformatics. Finally, we constructed relevant prognostic signature using machine learning and validated them using spatial transcriptomic data.

Results: Based on the differential genes of CAFs subpopulation trajectory differentiation, we identified two CRC subtypes (C1 and C2) in this study. Compared to C1, C2 exhibited worse prognosis, higher immune evasion microenvironment and high CAF characteristics. C1 was primarily associated with metabolism, while C2 was primarily associated with cell metastasis and immune regulation. By combining 101 combinations of 10 machine learning algorithms, we developed a High-CAF risk signatures (HCAFRS) based on the C2 characteristic gene. HCAFRS was an independent prognostic factor for CRC and, when combined with clinical parameters, significantly predicted the overall survival of CRC patients. HCAFRS was closely associated with epithelial-mesenchymal transition, angiogenesis, and hypoxia. Furthermore, the risk score of HCAFRS was mainly derived from CAFs and was validated in the spatial transcriptomic data.

Conclusion: In conclusion, HCAFRS has the potential to serve as a promising prognostic indicator for CRC, improving the quality of life for CRC patients.

Colorectal cancer (CRC) remains a highly prevalent gastrointestinal neoplasm, presenting significant prevalence and lethality rate. DEAD/H box RNA helicase 10 (DDX10) has been proposed as a potential oncogene in CRC, the specific action mechanism by which DDX10 modulates the aggressive biological cellular events in CRC remains implicitly elucidated, however. During this study, DDX10 expression was detected via RT-qPCR and Western blotting. Cell proliferation was estimated via EDU staining. TUNEL staining and Western blotting appraised cell apoptosis. Cell stemness was evaluated by sphere formation assay, RT-qPCR, Western blotting as well as immunofluorescence staining. Relevant assay kit examined aldehyde dehydrogenase (ALDH) activity. Western blotting and immunofluorescence staining also detected autophagy. DDX10 was hyper-expressed in CRC cells. Down-regulation of DDX10 hampered cell proliferation, aggravated the apoptosis while eliminated the ability to form spheroid cells in CRC. In addition, DDX10 deletion improved ATG10 expression and therefore activated autophagy in CRC cells. Consequently, ATG10 depletion or treatment with autophagy inhibitor 3-Methyladenine (3-MA) partially compensated the influences of DDX10 silencing on the proliferation, apoptosis and stemness of CRC cells. Accordingly, DDX10 deficiency may aggravate autophagy mediated by ATG10 to impede cell proliferation, stemness and facilitate cell apoptosis, hence blocking the progression of CRC.

Purpose: Cancer is a life threatening disease with negative impact on quality of life and psychological well-being. In international studies, one-to-one peer support and counseling have been shown to improve the psychological well-being of cancer patients. In the study presented, we developed and evaluated an innovative program of peer-coaching. In this program at the University Hospital of Freiburg, cancer survivors were trained to support peers by sharing experience.

Methods: In the project, N = 25 cancer survivors were trained to conduct supportive one-to-one conversations with acute patients or patients in aftercare. Based on a prospective observational study, patients were interviewed using questionnaires before and after the conversations. We assessed expectations and experiences with the peer-coaching as well as psychosocial parameters (PHQ9, GAD7, SSUK, NCCN-distress thermometer).

Results: A total of 52 patients had at least one contact with a peer-coach. Most of the patients attended 1-3 sessions. In total, 85 contacts pairing peer-coaches with patients were conducted. Patients showed on average a high level of distress but a low rate of psychiatric comorbidity. The supportive conversations met the patients` needs. Sharing experiences and empowerment were the most relevant benefits for the patients. Both patients and trained peers showed high satisfaction levels with the program.

Conclusion: Our findings support the feasibility and utility of a peer-coaching program in which trained cancer survivors, acting as peer-coaches, support other patients during or after their oncological treatment. In a further study, the efficacy of peer-coaching should be investigated based on a randomized-controlled trial.

Trial registration: The trial was registered in the German Clinical Trials Register (No. DRKS DRKS00017500) on 12.12.2019.

Purpose: This research aimed to clarify the metastatic patterns of subcarinal, right and left recurrent laryngeal nerve lymph nodes in thoracic esophageal squamous cell carcinoma and to investigate appropriate strategies for lymph node dissection.

Methods: Patients with thoracic esophageal squamous cell carcinoma receiving esophagectomy from December 2020 to April 2024 were retrospectively analyzed. Risk factors for subcarinal, right and left recurrent laryngeal nerve lymph nodes metastasis were determined by chi-square test and multivariate logistic regression analysis. We visualized the metastasis rates of these specific lymph nodes based on the different clinicopathological characteristics. Correlation between subcarinal, right and left recurrent laryngeal lymph nodes metastasis and postoperative complications were also analyzed.

Results: A total of 503 thoracic esophageal squamous carcinoma patients who underwent esophagectomy were enrolled. The metastasis rates of subcarinal, right and left recurrent laryngeal nerve lymph nodes were 10.3%, 10.3%, and 10.9%, respectively. The lymphovascular invasion status and tumor location were the significant predictors for subcarinal and right recurrent laryngeal nerve lymph nodes metastasis, respectively (P < 0.001 and P = 0.013). For left recurrent laryngeal nerve lymph node metastasis, younger age (P = 0.020) and presence of lymphovascular invasion (P = 0.009) were significant risk factors. Additionally, pulmonary infection is the most frequent postoperative complication in patients with dissection of subcarinal, right and left recurrent laryngeal lymph nodes. There was no significant difference in the incidence of anastomotic leakage (P = 0.872), pulmonary infection (P = 0.139), chylothorax (P = 0.702), and hoarseness (P = 0.179) between the subcarinal lymph node dissection cohort and the reservation cohort. The incidence of hoarseness significantly increased in both right (P = 0.042) and left (P = 0.010) recurrent laryngeal nerve lymph nodes dissection cohorts compared by the reservation cohorts, with incidence rates of 5.9% and 6.7%, respectively.

Conclusions: The metastasis rates of subcarinal, right and left recurrent laryngeal nerve lymph nodes in thoracic esophageal squamous cell carcinoma were all over 10%. The dissection of subcarinal lymph nodes does not increase postoperative complications risk, while recurrent laryngeal nerve lymph nodes dissection significantly increases the incidence of hoarseness. Thus, lymph node dissection of subcarinal lymph nodes should be conducted routinely, while recurrent laryngeal nerve lymph nodes dissection may be selectively performed in specific patients.

Purpose: Proper management of subcentimeter thyroid nodules remains challenging for both clinicians and patients. Conducting extensive sonographic research using a safe and inexpensive tool for identifying thyroid nodules is necessary. The aim of this study was to identify whether having the highest-risk ultrasound (US) characteristic suggests that US-guided fine-needle aspiration (FNA) biopsy of subcentimeter nodules is more appropriate for the identification of malignancy than active surveillance (AS) or surgery.

Methods: The data of patients with highly suspicious subcentimeter thyroid nodules and US characteristic data who underwent surgery were retrospectively examined.

Results: Among a total of 556 subcentimeter nodules, 223 (40.1%) were benign, and 333 (59.9%) were malignant, with a mean maximal nodule size of 8.1 mm. In addition to age younger than 45 years, several US features were significantly associated with malignancy: irregular margins, the presence of microcalcifications, and taller-than-wide shapes (P < 0.001). Multivariate analysis also revealed that a taller-than-wide shape (OR = 8.988, P = 0.0015) was an independent factor associated with malignancy in subcentimeter thyroid nodules. The diagnostic performance of preoperative FNA was classified as a malignancy, with a sensitivity of 98.4%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 76.9%.

Conclusions: This is one of the few reports based on actual data of the most suspicious US features in subcentimeter thyroid nodules. A taller-than-wide shape US feature is most significantly associated with malignancy. FNA is a simple, accurate, and reliable preoperative method for diagnosing malignant subcentimeter thyroid nodules with highly suspicious US characteristics. AS was less appropriate than FNA for subcentimeter nodules with a taller-than-wide shape, especially in patients ≤ 45 years of age.

Triple negative breast cancer (TNBC) is most aggressive type of breast cancer with multiple invasive sub-types and leading cause of women's death worldwide. Lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) causes it to spread rapidly making its treatment challenging due to unresponsiveness towards anti-HER and endocrine therapy. Hence, needing advanced therapeutic treatments and strategies in order to get better recovery from TNBC. Artificial intelligence (AI) has been emerged by giving its high inputs in the automated diagnosis as well as treatment of several diseases, particularly TNBC. AI based TNBC molecular sub-typing, diagnosis as well as therapeutic treatment has become successful now days. Therefore, present review has reviewed recent advancements in the role and assistance of AI particularly focusing on molecular sub-typing, diagnosis as well as treatment of TNBC. Meanwhile, advantages, certain limitations and future implications of AI assistance in the TNBC diagnosis and treatment are also discussed in order to fully understand readers regarding this issue.

Background: High-grade non-intestinal-type sinonasal adenocarcinoma (non-ITAC) is a rare and aggressive form of adenocarcinoma with poor prognosis. The current standard treatment approach involves surgery combined with radiation therapy. However, there is a need for exploring additional treatment modalities to improve patient outcomes.

Case presentation: We present a case of a 65-year-old male patient who presented with pain in the right maxillary sinus and was diagnosed with high-grade non-ITAC following surgery. Postoperative pathology revealed tumor invasion into bone tissue and vascular invasion, necessitating further treatment. The patient underwent radiation therapy, followed by immunotherapy with carilizumab combined with chemotherapy. During the maintenance immunotherapy period, tumor progression was observed, and genetic testing identified EGFR and TP53 mutations. Consequently, the patient was treated with gefitinib, a targeted therapy drug. Notably, the patient's lung metastases showed a gradual reduction in size, indicating a favorable treatment response. The patient is currently undergoing oral treatment with gefitinib.

Conclusions: This case report highlights the potential benefit of combining immunotherapy and targeted therapy in the treatment of high-grade non-ITAC. Despite the rarity of this cancer type, this approach may offer an alternative treatment strategy for patients with this aggressive disease. We hope that this case can contribute to a deeper understanding of high-grade non-ITAC and promote the application of immunotherapy and targeted therapy in improving survival rates for patients with this condition.

Purpose: This study aims to determine whether Pokemon regulates Bim activity in colorectal carcinoma (CRC) carcinogenesis.

Methods: Clinical tissue samples were analyzed to detect the expression and clinicopathological significance of Pokemon and Bim in CRC. Proliferation, apoptosis, and invasion assays were conducted to identify the regulatory effect of Pokemon on Bim. The combined treatment effects of Pokemon knockdown and diamminedichloroplatinum (DDP) were also examined.

Results: Immunohistochemical analysis of 80 samples of colorectal epithelia (CRE), 80 cases of colorectal adenoma (CRA), and 160 of CRC samples revealed protein expression rates of 23.8%, 38.8%, and 70.6% for Pokemon, and 88.8%, 73.8%, and 31.9% for Bim, respectively. A significant negative correlation was observed between Pokemon and Bim expression across the CRE, CRA, and CRC lesion stages. In CRC, higher Pokemon and lower Bim expression correlated with higher histological grades, advanced Dukes stages, and increased cancer invasion. In both LoVo and HCT116 cells, overexpression of Pokemon significantly reduced Bim expression, leading to increased proliferation, resistance to anoikis, and cell invasion. Additionally, Pokemon overexpression significantly decreased DDP-induced Bim expression, reduction of anti-apoptosis and invasion, whereas Pokemon knockdown resulted in the opposite effects.

Conclusion: These findings suggest that Pokemon inhibits Bim transcription, thereby promoting CRC proliferation, resistance to apoptosis, invasion, and advancing histological grade and Dukes staging. Pokemon knockdown enhances the therapeutic efficacy of DDP in the treatment of CRC.