Translational cancer research最新文献

Background: Timely diagnosis of borderline ovarian tumors (BOTs) is crucial for preserving fertility and ovarian function. However, current markers for detecting BOTs lack effectiveness. This research aims to identify and validate the role of small molecular markers in diagnosing BOTs. Six small molecule markers-human epididymis protein 4 (HE4), carbohydrate antigen 125 (CA125), fibrinogen (FIB), D-dimer (DD), platelet (PLT), and homocysteine (HCY)-were identified as candidate markers.

Methods: Candidate markers were evaluated using the receiver operating characteristic (ROC) curve to assess their diagnostic efficacy for BOTs. Suitable markers were chosen through statistical methods to develop a risk prediction model. The model's diagnostic performance was assessed using parameters such as the area under the ROC curve (AUC), Youden index, sensitivity, and specificity.

Results: There were significant differences in the levels of HE4, CA125, FIB, and DD between the group of BOTs and benign ovarian tumors. while PLT and HCY levels did not show significant variation. Notably, DD, with an AUC of 0.818, demonstrated utility in diagnosing BOTs. Building on this, a risk prediction model was created based on the diagnostic value of DD and HE4, resulting in an AUC of 0.852, particularly effective in diagnosing serous BOTs (AUC: 0.941). Significant diagnostic value was also observed in ovarian tumors with a diameter less than 4 cm (AUC: 0.772).

Conclusions: Changes in DD levels in BOTs patients can be utilized for disease diagnosis, especially when combined with HE4, resulting in improved diagnostic efficiency.

Background: Given the role of inflammation in cancer progression, the systemic immune-inflammation index (SII, defined as platelet × neutrophil/lymphocyte) has been suggested as an emerging prognostic marker in several solid malignant neoplasms. However, there are few studies on the prognostic value of SII in patients with limited-stage small cell lung cancer (LS-SCLC), and the optimal threshold of SII remains unclear in this population. This study calculated the optimal threshold of SII by a reasonable method and explored its association with survival outcomes.

Methods: This retrospective study reviewed clinical data of 572 patients with LS-SCLC. The threshold for SII was determined using an outcome-based method by maximizing the log-rank test statistic and the survival differences. Continuous time-dependent receiver operating characteristic curves (time-dependent ROC curves) were used to clarify the predictive ability of SII.

Results: The thresholds of SII for overall survival (OS) and progression-free survival (PFS) were both 760.6, based on which patients were divided into low [292 cases (51.0%)] and high [280 cases (49.0%)] SII groups. The area under the time-dependent ROC curves of SII in 12-, 24-, and 36-months were 0.727, 0.708, and 0.680, respectively. The overall median OS and PFS were 26.0 months [95% confidence interval (CI): 23.8-28.2] and 13.0 months (95% CI: 11.3-14.7), respectively. Significantly improved OS [35.0 (95% CI: 30.0-40.0) vs. 19.0 months (95% CI: 17.1-20.9), P<0.001] and PFS [20.0 (95% CI: 17.3-22.7) vs. 11.0 months (95% CI: 9.9-12.1), P<0.001] was seen in the low SII group than that in the high SII group. In the multivariable survival analysis, SII remained an independent prognostic factor for OS [hazard ratio (HR): 1.699; 95% CI: 1.374-2.100; P=0.001] and PFS (HR: 1.482; 95% CI: 1.214-1.809; P<0.001).

Conclusions: Our study demonstrates that elevated SII is an independent adverse prognostic factor for LS-SCLC.

Background: Lung cancer is the most common cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) is the main type of lung cancer. Long non-coding RNA ZEB1 antisense 1 (lncRNA ZEB1-AS1) is derived from the promoter region of the transcriptional repressor ZEB1. In bladder cancer and glioblastoma, lncRNA ZEB1-AS1 promotes the expression of ZEB1 and cancer progression, and is associated with a poor prognosis. However, its role in NSCLC tumor progression remains unclear. This study aims to investigate its possible role in NSCLC tumor progression.

Methods: In this study, overexpressed and silenced lncRNA NSCLC cell lines of ZEB1-AS1 were constructed, epithelial-mesenchymal transition (EMT)-related proteins were detected, and the invasion and migration abilities of the cells were examined. Moreover, the radioimmunoprecipitation (RIP) assay was used to examine whether the increase in the STAT3 protein level caused by ZEB1-AS1 overexpression was based on the promotion of STAT3 messenger RNA (mRNA) translation by AUF1, and the dual-luciferase assay was used to verify the results.

Results: The overexpression of ZEB1-AS1 increased the protein levels of ZEB1 and STAT3, promoted the occurrence of EMT, and enhanced the invasion and migration abilities of lung cancer cells. The RIP results showed that both lncRNA ZEB1-AS1 and ZEB1 mRNA bind to AUF1, but no binding between AUF1 and STAT3 mRNA was detected. The bioinformatics analysis and the results of the dual-luciferase experiments showed that STAT3 was the target gene of microRNA 519d (miRNA519d), and that lncRNA ZEB1-AS1 also binds to miRNA519d.

Conclusions: LncRNA ZEB1-AS1 formed the competing endogenous RNA (ceRNA) regulatory network of lncRNA ZEB1-AS1~miRNA519d~STAT3 as the molecular sponge, and promoted the expression of STAT3, thus promoting the occurrence of EMT in lung cancer cells.

Background: Adenanthin, a diterpenoid isolated from the leaves of Rabdosia adenantha, has anti-tumor activities. However, its role and mechanism in pancreatic cancer are unclear. This study aims to elucidate the mechanism of adenanthin induced death of pancreatic cancer cells by regulating hydrogen peroxide (H₂O₂) and reactive oxygen species (ROS) levels.

Methods: Adenanthin was used to detect its cell activity on pancreatic cancer cells (Aspc-1) using the Cell Counting Kit-8 (CCK-8) and colony forming assays. Hoechst 33258 fluorescence staining and flow cytometry related experiments were used to detect its impact on apoptosis and cell cycle of Aspc-1 cells. Western blot was used to detect the expression of cycle and apoptosis related proteins, and the concentration of H₂O₂ and ROS in Aspc-1 cells were measured by content determination kit. A mouse tumor transplantation model was established and the expression of related proteins after administration of adenanthin was detected.

Results: Adenanthin can inhibit the proliferation and induce apoptosis of pancreatic cancer cells. The results of propidium iodide (PI) single staining flow cytometry showed that adenanthin significantly blocked Aspc-1 cells in the S phase and G2/M phase. Further exploration of its mechanism found that adenanthin significantly increased the content of H₂O₂ and ROS in cells, and realized the inhibitory effect on pancreatic cancer cells by regulating apoptosis and cyclin. The transplanted tumor model in mice was consistent with the results of cell experiments.

Conclusions: In pancreatic cancer, adenanthin can significantly increase the content of H₂O₂ and ROS, induce apoptosis and cycle arrest of pancreatic cancer cells, and ultimately play a role in treating pancreatic cancer. Therefore, adenanthin is expected to become a new drug against pancreatic cancer.

Background: The increasing occurrence of thyroid cancer (TC), particularly papillary thyroid cancer (PTC), highlights our need for better diagnostic indicators and new therapeutic targets. Aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) plays a crucial function in multiple tumor types. Accordingly, we investigated the oncogenic function and molecular pathways associated with ARNTL2 in PTC.

Methods: Our study utilized the The Cancer Genome Atlas (TCGA) database to examine ARNTL2 expression, which was subsequently confirmed in PTC tissues and cell lines employing quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB) analysis. Herein, we evaluated PTC cell proliferation, cell cycle progression, apoptosis, migration, and invasion through Cell Counting Kit-8 (CCK-8), flow cytometry, wound-healing assay, and Transwell assay. Eventually, we determined the mechanism behind ARNTL2 in PTC via WB.

Results: In PTC, a significant ARNTL2 upregulation was observed, which exhibited a positive correlation with enhanced tumor aggressiveness. Additionally, knocking down ARNTL2 facilitated apoptosis, besides impeding cell cycle progression, cell proliferation, migration, and invasion, alongside epithelial-mesenchymal transition (EMT) in PTC. However, the outcomes were reversed when ARNTL2 was overexpressed. Enhanced expression of ARNTL2 led to an elevation in phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) phosphorylation within PTC cells, while the administration of alpelisib effectively mitigated the effects induced by upregulated ARNTL2 on EMT, PTC cell proliferation, apoptosis, and invasion.

Conclusions: Elevated ARNTL2 levels enhance PTC proliferation, migration, invasion, and EMT while inhibiting apoptosis through the cell cycle signaling, elucidating its potential as a diagnostic PTC biomarker.

Background: For unresectable or metastatic gastric/gastroesophageal junction cancer (G/GEJC), immune checkpoint inhibitors (ICIs) plus platinum-based doublet chemotherapy [FOLFOX (leucovorin, fluorouracil, and oxaliplatin) and XELOX (capecitabine and oxaliplatin)] are currently recommended as the standard first-line treatment. Research indicates that ICIs combined with paclitaxel have a synergistic effect, but the evidence is insufficient. This multicenter, retrospective study aimed to compare the efficacy and tolerability of ICIs [mainly anti-programmed cell death-1 (anti-PD-1) antibodies] plus a paclitaxel-based chemotherapy regimen (ICIs plus PTX) vs. an oxaliplatin-based regimen (ICIs plus OXA) as the first-line therapy for advanced G/GEJC.

Methods: This research involved 123 patients with advanced G/GEJC at three institutions in China from August 2019 to June 2022. The ICIs plus PTX group included 58 patients, whereas the ICIs plus OXA group included 65 patients. We compared the efficacy and safety of two treatment regimens.

Results: Fifty-eight patients (47.2%) received ICIs plus PTX, and 65 patients (52.8%) received ICIs plus OXA. The median progression-free survival (PFS) [8.07 vs. 7.23 months; hazard ratio (HR) =0.845; 95% confidence interval (CI): 0.568-1.257; P=0.40] and overall survival (OS) (14.83 vs. 15.10 months; HR =0.852; 95% CI: 0.536-1.355; P=0.50) were not significantly different between the ICIs plus PTX group and the ICIs plus OXA group. The objective response rate (ORR) (50.0% vs. 53.8%, P=0.67) and disease control rate (DCR) (98.3% vs. 93.8%, P=0.21) were also similar between the PTX and OXA groups, and both treatments exhibited manageable side effects. Subgroup analysis based on patient characteristics suggested that PFS HRs favored the ICIs plus PTX subgroup in patients aged <65 years or without liver metastasis.

Conclusions: In summary, ICIs plus PTX are as effective as ICIs plus OXA for treating advanced G/GEJC with manageable toxicity. The advantages of ICIs plus PTX in terms of adverse events (AEs) may support it as an alternative to ICIs plus OXA.

Metastases to the lesser sac (also known as the omental bursa) and its contents are frequently seen in advanced ovarian cancer. This would require a thorough and meticulous intra-operative surgical exploration and mapping for patients requiring radical supracolic omentectomy requiring sacrifice of the gastro-epiploic arcade. We describe an educational surgical technique with maximum effort to preserve the right and left gastric arteries, when the right and left gastro-epiploic arteries and short gastric arteries are divided. These steps are demonstrated with attention to anatomical landmarks of the lesser sac to minimise intraoperative and postoperative morbidity. This surgical approach will not only spare the gastric branches of the vagus nerve (rami gastrici) but also prevent gastric ischaemic changes. We describe the case of a 77-year-old female patient diagnosed with stage 3C high grade serous ovarian/tubal cancer on the neoadjuvant chemotherapy pathway, undergoing delayed debulking surgery. The gynaecological oncology surgeon should confidently hold detailed knowledge of upper abdominal anatomy in their armamentarium, to maximise the safety and efficacy of ultra-radical surgery to achieve R0 (no residual disease); which is a single independent risk factor for survival. This video demonstrates a challenging case with an undesirable location of metastatic disease requiring advanced upper abdomen surgical skills and knowledge, with specific consideration of intraoperative multidisciplinary decision-making.

Background: The causes of death in extramammary Paget's disease (EMPD) patients are currently unclear. The authors aimed to examine mortality patterns among current survivors of EMPD.

Methods: We conducted a retrospective cohort analysis utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2000 to 2019, focusing on patients diagnosed with EMPD. Standardized mortality ratios (SMRs) were employed to assess mortality rates in EMPD patients compared to the general population.

Results: Our study comprised 1,002 patients diagnosed with EMPD, among whom 437 (43.6%) patients died during the follow-up period. In patients staged as localized, all malignant tumors accounted for 29.71% (n=101) of all deaths. Except for the 5-<10 years SMR being higher than the general population, no substantial difference was observed in SMR between EMPD and the general population for all causes of death. Among patients with regional/distant EMPD, 55 (56.70%) individuals died from all malignant tumors, while 42 (43.30%) individuals died from non-cancer causes. Throughout the follow-up period, the all-cause mortality rate was higher than that of the general population [SMR, 1.91; 95% confidence interval (CI): 1.55-2.33]. Cardiovascular and cerebrovascular diseases were the most common non-cancer causes of death in the whole cohort. Compared to patients aged 60-70 years and those aged 70 years and above, patients under 60 years had a lower SMR for all-cause mortality.

Conclusions: Non-cancer related fatalities represent over 70% of cases in localized stage and 40% in regional/distant stage. Although the risk of all malignant tumors death is higher than that of the standard population, the overall risk of death for patients with localized stage is not increased. These data provide most up-to-date and comprehensive analysis of mortality causes among EMPD patients.