Translational cancer research最新文献

Background: Sorafenib resistance poses a significant challenge in the management of advanced hepatocellular carcinoma (HCC). Therefore, understanding the mechanisms behind sorafenib resistance is crucial for reversing resistance and enhancing the therapeutic effect of this anti-cancer drug. In this study, the molecular mechanisms underlying the ability of emodin to reverse sorafenib resistance were examined in sorafenib-resistant Huh7 (Huh7SR) cells.

Methods: In this study, we successfully established a Huh7SR cell line that was subsequently divided into four treatment groups: control, sorafenib, emodin, and a combination of sorafenib and emodin. The cell viability, migration, invasion, colony formation capacity, and apoptosis of cells were assessed using the Cell Counting Kit-8 (CCK-8), transwell, colony formation, flow cytometry, and Hoechst staining assays, respectively. Using western blot analysis, we investigated proteins associated with apoptosis, epithelial-mesenchymal transition (EMT), and AKT signaling to explore the molecular mechanisms of emodin-dependent sorafenib resistance reversal.

Results: Notably, sorafenib and emodin combination treatment exhibited a synergistic effect, enhancing chemosensitivity and apoptosis while inhibiting proliferation, colony formation, migration, and invasion. Additionally, western blotting showed that emodin significantly enhanced sorafenib's ability to reverse EMT, induce apoptosis, and inhibit AKT signaling in Huh7SR cells.

Conclusions: Our study demonstrated that emodin effectively enhances sorafenib sensitivity, promotes apoptosis, and reverses EMT in Huh7SR cells through inhibition of the Akt signaling pathway. A limitation of this study is the exclusive use of a single cell line. Overall, emodin can enhance sorafenib's efficacy as an adjuvant therapy in the treatment of HCC.

[This corrects the article DOI: 10.21037/tcr-22-2177.].

Background: Vulvar cancer is a relatively rare malignant tumor that receives less attention than other gynecological malignancies. Short-video apps are playing an important role in promoting health. This study evaluated the quality of videos about vulvar cancer on YouTube with the aim of making facts-based recommendations and promoting public health engagement.

Methods: On May 15, 2024, the term "vulvar cancer" was searched on YouTube, and the top 100 videos identified in the search were chosen for our research. We evaluated the completeness of each video using six dimensions. The video quality was evaluated using the DISCERN instrument (Quality Criteria for Consumer Health Information), the Journal of the American Medical Association (JAMA) benchmark criteria, the Patient Education Materials Assessment Tool (PEMAT), and the Global Quality Scale (GQS). Correlations between video data, DISCERN, JAMA, PEMAT, and GQS scores were analyzed.

Results: Among the 65 videos that were included in this study, the majority (64.6%) were posted by educational and training institutes. The quality of the videos submitted by physicians was comparatively good, as indicated by the GQS scores (P=0.045). The relationships between the DISCERN categorization score and duration (P<0.001), views per day (P=0.02), likes per day (P<0.001), comments per day (P=0.03), PEMAT actionability (P<0.001), and GQS scores (P<0.001) were statistically significant. Additionally, there was a strong positive correlation between the GQS score and video length.

Conclusions: The quality of videos about vulvar cancer on YouTube is unsatisfactory. However, several measures can be adopted in the future to make YouTube a more practical tool for promoting the prevention and cure of vulvar cancer.

Background: Progression of chronic liver dysfunction influenced by long-term chemotherapy or repeated hepatectomy might be related to patient overall survival as well as tumor factors in colorectal liver metastasis (CLM) patients. Our aim of this study was to clarify the relationship between fibrotic liver damage and malignant behaviors of CLM malignancy or its long-term survivals by the retrospective cohort study.

Methods: We examined the relationship between tumor-related factors or six liver fibrosis-associated parameters, including platelet count, hyaluronic acid (HA), mac-2 binding protein glycosylation isomer (M2BPGi), type IV collagen 7S (T4C7), aspartate aminotransferase-to-platelet ratio index (APRI), The fibrosis-4 (Fib-4) index, and clinicopathological parameters, surgical records, and postoperative patient survival in the 45 consecutive patients with CLM who underwent radical hepatectomy.

Results: Fibrotic parameters were platelet count of 23.0±8.5 ×10⁴/µL, HA level of 68.9±82.3 ng/mL, M2BPGi of 0.87±0.48 ng/mL, and type IV collagen level of 5.74±3.76 ng/mL. Platelet count was significantly correlated with HA level (P<0.05) and tended to be correlated with M2BPGi levels (P=0.056). HA level was significantly associated with albumin level (P<0.05). Overall survival in this series showed five-year overall survivors after hepatectomy in 44 patients (98%), but cancer-related deaths were observed in only one patient. Patients with higher grades and increased bilirubin levels demonstrated significantly lower cancer-free survival (P<0.05), but fibrotic parameters were not associated with prognostic factors.

Conclusions: Fibrotic markers indicating chemotherapy or repeated surgical liver injury were not significant predictive factors reflecting cancer malignant behaviors or patient overall survival, contrary to our hypothesis. The current overall survival status using various modalities for cancer recurrence is satisfactory under our present perioperative management.

Background: There is currently no recognized assessment system to predict disease outcomes for stage I non-small cell lung cancer (NSCLC). This research aimed to develop a prognostic scoring system for predicting 5-year overall survival (OS) of individuals with stage I NSCLC following definitive therapeutic intervention. Additionally, the optimal number of examined lymph nodes (ELNs) count for tumors no larger than 30 mm was determined.

Methods: Patients (n=22,617) diagnosed with stage I NSCLC from 2007 to 2015 who underwent definitive treatment (pulmonary lobectomy, pulmonary sublobectomy, or radiotherapy) were identified from the Surveillance, Epidemiology, and End Results (SEER) database. There were 400 Chinese patients with stage I NSCLC diagnosed in 2017 enrolled for external validation. The nomogram was constructed based on gradient boosting machine. The optimal ELNs in patients with tumors ≤30 mm and node-negative undergoing pulmonary lobectomy or pulmonary sublobectomy were determined using log-rank test and validated by multivariable analysis.

Results: Age at diagnosis, histology, differentiated grade, tumor staging, number of ELNs, and definitive treatment pattern were recognized as important factors for 5-year OS. The prognostic scoring system exhibited superior discrimination accuracy, calibration ability, and net clinical benefit compared to the tumor, node, metastasis (TNM) staging system. For patients with tumors ≤30 mm, more than 10 and 20 ELNs demonstrated the maximum OS difference during lobectomy and sublobectomy, respectively.

Conclusions: This prognostic scoring system will anticipate the prognosis of stage I NSCLC patients after radical treatment, thereby offering individualized treatment recommendations for both clinicians and patients. A minimum of 10 ELNs during lobectomy and 20 ELNs during sublobectomy are necessary for small-sized NSCLC.

Background: Colorectal cancer (CRC) is the most common malignant tumor of the digestive tract worldwide, however, the potential targets for CRC and its subsites (colon cancer & rectum cancer) are less known. The aim of this study is to explore potential therapeutic targets for CRC.

Methods: A proteome-wide genome-wide association studies (GWAS) in 35,559 Icelanders with 4,907 plasma proteins was used as instrumental variables (P value <5×10^-8). The discovery stage consisted of the CRC GWAS with the largest sample size (CRC: 14,886 cases; colon: 3,793 cases; rectum: 2,091 cases). The significant proteins were further validated in the FinnGen study with 5,458 CRC cases (3,292 colon + 2,017 rectum). We identified relevant protein loci in CRC by two sample Mendelian randomization (MR) [false discovery rate (FDR) <0.05], colocalization analysis was used to further determine the relevance between CRC and plasma proteins, enrichment analysis and drug prediction were used to predict protein function.

Results: A total of 31 proteins were found to be in robust causal associations with CRC and the proteins' effects displayed anatomic site-specificity in MR analysis. The subsequent colocalization analysis pinpointed that CHDRL2 had a shared region with CRC and its two subsites, suggesting the importance of targeting it. Besides, IGF2R and ENPEP displayed anatomic site-specificity to colon cancer while ASRGL1 was strongly correlated only with the risk of rectal cancer. Enrichment analysis revealed functions of these proteins in CRC, and DrugBank showed their target drug.

Conclusions: In summary, our study has identified a common protein, CHDRL2, as the drug targets for CRC and its subsites. Besides, IGF2R and ENPEP displayed anatomic site-specificity to colon cancer while ASRGL1 was strongly correlated only with the risk of rectal cancer.

Background: Adult soft tissue sarcoma (SARC) is a highly aggressive malignancy. A growing number of long non-coding RNAs (lncRNAs) have been linked to malignancies, and many researchers consider lncRNAs potential biomarkers for prognosis. However, there is limited evidence available to determine the role of lncRNAs in the prognosis of SARC. In this study, we collected The Cancer Genome Atlas (TCGA) data to identify prognosis-related lncRNAs for SARC and explore the relationship between lncRNAs and gene expression.

Methods: TCGA datasets, which included 259 samples, served as data sources in this study. Univariable Cox regression analysis, robust analysis, and multivariable Cox regression analysis were used to construct a 5-lncRNA signature Cox regression model. Then, based on the median risk score, high- and low-risk groups were identified. The Kaplan-Meier method was applied to survival analysis in the training set, testing set, complete set, and different pathological type sets. To explore the relationship between lncRNAs and messenger RNAs (mRNAs), differentially expressed mRNAs (DEmRNAs) between the high- and low-risk groups were identified. The function of DEmRNAs was predicted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The relationships between the 5 lncRNAs and DEmRNAs were calculated using the Spearman correlation coefficient. A total of 18 DEmRNAs that showed a strong correlation with risk score (|Spearman's r|>0.6) in leiomyosarcoma (LMS) samples were identified, and a protein-protein interaction (PPI) network was built using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database.

Results: A Cox regression model was built in this study with the risk score= (-0.5698*AC018645.2) + 0.1732*LINC02454 + 0.387*ERICD + 0.6262*DSCR9 + 0.9781*AL031770.1. The study found that this 5-lncRNA signature could predict prognosis well, especially in LMS, a subtype of SARC, with P value =1.19e-06 [hazard ratio (HR) 6.134, 95% confidence interval (CI): 2.951-12.752]. Additionally, 44 DEmRNAs were observed between the high- and low-risk groups, and the expression levels of DEmRNAs in LMS samples differed from other pathology types. The PPI network analysis revealed that MYH11, MYLK, and CNN1 were the most important hub genes among the 18 DEmRNAs, all of which are essential for muscle function.

Conclusions: In this study, a predictive clinical model for SARC was successfully established, showing better prediction accuracy in patients with LMS. Importantly, we identified MYH11, MYLK, and CNN1 as potential therapeutic targets for SARC.