BMC Cancer最新文献

Background: Patients with BRAF 600E mutated mCRC are associated with specific clinicopathological features and poor prognosis. The relative efficacy of first-line FOLFOXIRI triplet chemotherapy or doublet chemotherapy combined with bevacizumab in patients with BRAF 600E mutated mCRC remains controversial.

Methods: BRAF V600E-mutated mCRC patients from 3 institutions were included. The clinicopathological characteristics of the enrolled patients were analyzed. Overall survival (OS) of patients was divided into 4 fractions, including 0-25%, 25-50%, 50-75%,75-100% by quartile method. Patients with OS ranging from 0 to 25% were defined as the poor prognosis group, and patients with OS ranging from 75 to 100% were defined as the good prognosis group. A propensity score matching (PSM) analysis was performed to balance the baseline characteristics of patients treated with doublet chemotherapy and triplet chemotherapy combined with bevacizumab. Survival and tumor response of the two regimens were evaluated.

Results: A total of 125 patients with BRAF V600E-mutated mCRC were enrolled. The median OS of BRAF V600E-mutated mCRC was 14.9 months and the median PFS of first-line therapy was 6.1 months. According to the multivariate analysis and the difference in baseline characteristics between the poor prognosis group and the good prognosis group, poor differentiation and liver metastasis were negative independent prognostic factors for OS in patientsx with BRAF V600E-mutated mCRC. Patients treated with first-line triplets had a longer OS than those treated with doublets both before PSM (17.4 months vs. 13.4 months, p = 0.022) and after PSM (17.4 months vs. 10.4 months, p = 0.004). There was no significant benefit between triplet-drug group and doublet-drug group for PFS, ORR and DCR. Subgroup analysis showed that patients in the triplet-drug group had a better prognosis with the following favorable factors: age ≤ 60 years old, PS score of 0-1, liver metastases and multiple organ metastases.

Conclusion: The overall prognosis of BRAF V600E mutant mCRC patients is poor. Poor differentiation and liver metastases were negative independent prognostic factors for OS. First-line triplet-drug therapy was associated with better OS, especially in patients with good physical condition and high tumor burden.

Background: Telomere shortening and RNA pseudo-uridylation are common features of tumors. NOP10 is a member of the H/ACA snoRNP family, essential for maintaining telomerase activity and RNA pseudouridylation. NOP10 has been indicated to be substantially expressed in tumors such as breast and lung cancers and is associated with poor prognosis. Currently, no investigation exists on NOP10 in pancreatic cancer (PC). This is the first investigation to elucidate the impact on tumorigenesis and prognostic value of NOP10 in pancreatic adenocarcinoma (PAAD).

Method: NOP10 expression and its survival prognostic significance were analyzed via clinical PAAD data from the TCGA database and NOP10 expression in other tumors from the GEPIA database. Furthermore, the NOP10 expression and survival prognosis in clinical samples were validated by qRT-PCR. In-vitro experiments were carried out to elucidate the impact of NOP10 on the biological function of PC cells.

Results: It was revealed that NOP10 expression was increased in PC tissues than in the normal pancreatic tissues. High NOP10 expression was markedly linked with poorer prognosis. NOP10 may be involved in focal adhesion, channel activity, cAMP signaling pathway, the interaction of neuroactive ligand-receptor, and cell adhesion molecules cams. NOP10 was associated with the tumour immune microenvironment and drug sensitivity. Down-regulation of NOP10 expression suppressed PC cells' ability to proliferate, migrate, and invade.

Conclusions: This investigation elucidated the prognostic and predictive importance of NOP10 in PAAD and revealed that NOP10 is associated with poor prognostic features, survival prognosis and TIME. Knockdown of NOP10 inhibits the progression of PAAD.

Background: The Androgen Receptor (AR) has emerged as an endocrine therapy target in Breast Cancer, exhibiting up to 80% expression in clinical cases. AR-V7, a constitutively activated splice variant of AR with a truncated ligand-binding domain (LBD), demonstrates ligand-independent transcriptional activity and resistance to nonsteroidal antiandrogens like Bicalutamide or Enzalutamide, targeting the LBD. In metastatic prostate cancer, elevated AR-V7 levels lead to therapeutic resistance and increased metastasis.

Methods: In this study, we evaluated the expression of AR and AR-V7 in cell lines and a cohort of 89 patients undergoing surgical intervention for treatment-naïve breast cancer. Further clinicopathological correlations and survival analysis were performed to evaluate the relationship between the AR and AR-V7 expression and clinical outcomes.

Results: AR-V7/AR-FL ratio was elevated in the TNBC cell line and downregulation of AR-FL upon AR antagonists' treatment led to a compensatory increase in AR-V7. Clinical samples showed significantly elevated expression of AR and AR-V7 in tumors compared to control cases. Further clinicopathological correlation revealed aggressive clinical traits, higher pathological grades, and poor survival with AR-V7 expression.

Conclusions: Our study unravels AR-V7 as a marker for poor clinical outcomes, predicting breast cancer aggressiveness, and encourages consideration of AR-V7 as a probable target for therapeutic intervention.

Background: Chemotherapy and immunotherapy for non-small-cell lung cancer (NSCLC) are gaining momentum. However, its long-term efficacy remains limited to only a small fraction of patients. Hence, it is crucial to identify reliable immunohistochemical biomarkers to facilitate the formulation of optimal treatment strategies and to predict therapeutic outcomes.

Methods: We retrospectively analyzed a cohort of 140 patients diagnosed with NSCLC who received chemotherapy or immunotherapy. Using bioinformatics analysis and machine learning techniques, we assessed the role of immunohistochemical biomarkers and clinical characteristics in developing a predictive model for treatment options and outcomes in this population.

Results: Our research has found that immunohistochemical biomarkers can accurately predict treatment regimens and progression-free survival in NSCLC patients with an accuracy rate of 82.1%. We identified an exclusive detection panel for the six vital biomarkers. Of particular note is the role of programmed cell death protein 1 ligand 1 (PD-L1) expression in guiding treatment selection, with high expression predicting better outcomes in the immunotherapy group at a cut-off value of 50%. Non-squamous patients who tested positive for thyroid transcription factor 1 had a longer median progression-free survival, while squamous patients who tested positive for p63 protein or cytokeratin 5/6 expression had a longer median progression-free survival.

Conclusions: The results of our study are highly encouraging, as they revealed a significant correlation between immunohistochemical biomarkers, therapeutic regimens, and prognosis. These findings indicate that our immunohistochemical detection panel has great potential for facilitating customization of therapeutic regimens to improve patient care. The insights gained from this study could help clinicians optimize treatment protocols and ultimately enhance clinical outcomes.

Background: The number of older patients with cancer is increasing with the progression of aging societies. In the current study, we sought to clarify the prognostic values of the geriatric nutritional risk index (GNRI) as a nutritional index and the neutrophil-to-lymphocyte ratio (NLR) as an inflammatory index in older patients with gastric cancer.

Methods: Between January 2007 and December 2016, a total of 197 consecutive gastric cancer patients aged ≥ 75 years who underwent radical gastrectomy were enrolled in this study. The prognostic values of preoperative GNRI and NLR were assessed using time-dependent receiver operating characteristic curve analysis, log-rank tests, and Cox regression analysis.

Results: The areas under the curve (AUCs) predicting 5-year overall survival (OS) were 0.668 for GNRI and 0.637 for NLR. The 5-year OS rates in the groups with low GNRI and NLR were 40.1% and 74.1% (p < 0.001), and those with high GNRI and NLR were 70.7% and 41.5% (p < 0.001), respectively. Multivariate analysis showed that GNRI (hazard ratio (HR): 0.584; 95% confidence interval (CI): 0.356-0.960; p = 0.034) and NLR (HR: 2.470; 95% CI: 1.503-4.059; p < 0.001) were independent predictors for OS. The GNRI-NLR score constructed with GNRI and NLR had a higher AUC (0.698) than those of GNRI or NLR alone and was an independent prognostic factor (HR, 0.486; 95% CI: 0.363-0.651; p < 0.001).

Conclusions: GNRI and NLR are useful prognostic biomarkers in older patients with gastric cancer aged ≥ 75 years. The GNRI-NLR score could contribute to a more personalized and holistic approach to cancer treatment in this patient population.

Background: Breast cancer is the most prevalent cancer worldwide. Belgium shows high age-standardized incidence rates, but also high survival rates. Like many health outcomes, breast cancer has been associated with multiple factors of socioeconomic status. This paper aims to (a) map educational differences in breast cancer incidence, mortality and death rates within 5 years of diagnosis, (b) update earlier trends in breast cancer mortality rates in Belgium for the 2004-2013 period and (c) investigate the role of fertility indicators as mediating factors in the association between education and breast cancer outcomes.

Methods: Data consisted of a linkage between the 2001 Belgian Census, register data on mortality and cancer incidence data (2004-2013) from the Belgian Cancer Registry. We calculated age standardized rates, rate ratios (Poisson regression) and hazard ratios (Cox regression) and furthermore also applied the method of Excess Portion Eliminated (EPE) in a mediation analysis of the fertility indicators. We stratified our analysis by age: younger than 50 (premenopausal) and 50 or older (postmenopausal).

Results: We observed striking differences in breast cancer incidence, all-cause and cause-specific death rates 5-years after diagnosis by educational level. Higher educated women had higher breast cancer incidence, but also lower all-cause and lower cause-specific death rates; adding up to zero differences in breast cancer mortality in the postmenopausal group and lower breast cancer mortality in the premenopausal group.

Conclusion: A notable shift in the social gradient occurred since the 1990's, favouring higher-educated women in recent years. Especially, with regards to survival after diagnosis there is potential for policy intervention. Stage at diagnosis played a crucial role, but differences between socioeconomic groups remained significant after including this parameter. While fertility indicators played a role, the impact was less pronounced than expected.

Introduction: Prophylactic chemotherapy (PC) has been suggested to be effective in prevention of post molar gestational trophoblastic neoplasia (PGTN) in patients with high-risk molar pregnancies. The goal of this study is to assess the efficacy of single dose methotrexate as PC in terms of spontaneous remission, time to remission, and progression to PGTN.

Materials and methods: Patients with molar pregnancy were recruited to the study and underwent cervical dilation and suction curettage. Patients who had pathologically proven complete hydatidiform mole were evaluated with abdominal ultrasonography to confirm complete evacuation and absence of remnants. These patients were allocated to two groups: group one received Methotrexate 50 mg/m2 via intramuscular injection, while group two did not. PGTN was defined according to the 2018 FIGO criteria. For patients with confirmed PGTN, the following variables were recorded: occurrence of metastasis, resistance to first-line chemotherapy and time to βHCG level normalization.

Results: Eighty patients were enrolled to the study, of which 22 cases (27.5%) received PC. It was found that PC with MTX did not significantly influence spontaneous remission (18 (81.8%) Vs 37 (63.7%), p value: 0.12) or time to remission (57 ± 22.5 Vs 61.24 ± 21.78 days, p value: 0.46) in high-risk molar pregnancies. Moreover, among patients in PC group and control group, 4 cases (18.2%) and 21 patients (36.3%) progressed to PGNT, respectively (p value: 0.12). Although patients in PC group tended to be diagnosed in lower stages compared to patients in control group, this difference was insignificance (p value: 0.95). Among patients who developed to PGTN, PC did not reduce the frequency of metastatic disease, resistance to first-line chemotherapy, or the time interval to serum βHCG level normalization (all p values > 0.05).

Conclusion: This study suggests that a single-dose MTX as PC may not be an effective therapeutic option for preventing PGTN in patients with high-risk molar pregnancy.

Background: The aim of this study was to assess the prognostic significance of serum direct bilirubin (DBIL) for patients newly diagnosed with myelodysplastic syndromes (MDS).

Methods: The clinical, laboratory, and follow-up data of MDS patients were collected, and the associations of DBIL levels with overall survival (OS) and leukemia-free survival (LFS) were analyzed.

Result: In total, 262 MDS patients were assigned to the high DBIL level group or the normal DBIL level group in the retrospective study. High DBIL was associated with older age, reduced hemoglobin, higher levels of β2-microglobin, lactate dehydrogenase, and serum ferritin, along with the number of co-mutations (> 1) and a higher frequency of ASXL1, KIT, and KRAS mutations. Multivariate analyses found that high DBIL level was an independent adverse predictor for OS (p = 0.002, hazard ratio = 2.723, 95%CI = 1.442-5.143) but not for LFS (p = 0.057, hazard ratio = 1.678, 95%CI = 0.986-2.857). A novel nomogram based on DBIL, sex, age, β2-microglobulin, lactate dehydrogenase, the Revised International Prognostic Scoring System (IPSS-R) was constructed, which demonstrated superior accuracy compared with the IPSS-R (C-index, 0.790 vs. 0.731, respectively).

Conclusion: An elevated DBIL level was identified as an independent adverse prognostic factor for MDS patients. An individualized prediction model was established and validated to improve prediction of OS and LFS.

Background: Patients with gastrointestinal cancer have a higher risk of malnutrition and postoperative infection.

Objective: To investigate the nutritional status of patients with gastrointestinal cancers and factors for postoperative infections.

Method: Based on the nutritional risk status, 294 patients with gastrointestinal tumours were divided into a nutritional risk group and a non-nutritional risk group, and the differences between the two groups were compared.

Results: Among the included patients, 128 were at preoperative nutritional risk (43.54%); there were significant differences between the two groups in terms of age (66.25 ± 11.73 vs. 58.36 ± 10.41 years, P < 0.001), percentage of gastric cancers (39.84% vs. 28.92%, P = 0.049), percentage of stage IV tumours (60.16% vs. 45.18%, P = 0.011), total protein (64.90 ± 6.82 vs. 67.21 ± 7.41 g/L, P = 0.007), albumin (38.32 ± 4.74 vs. 41.61 ± 5.10 g/L, P < 0.001) and haemoglobin (112.72 ± 22.63 vs. 125.11 ± 22.79 g/L, P < 0.001). Multivariate logistic regression analysis showed that risk factors for postoperative infections in patients included age ≥ 60 years (odds ratio [OR] = 2.266 95%CI = 1.357-4.134), Nutrition Risk Screening (NRS)-2002 score ≥ 3 (OR = 2.183, 95%CI = 1.218-4.102), alcohol history (OR = 2.505, 95%CI = 1.370-4.683), comorbid diabetes mellitus (OR = 2.110, 95%CI = 1.381-4.023) and surgical time ≥ 6 h (OR = 2.446, 95%CI = 1.359-4.758).

Conclusion: Patients with gastrointestinal cancers are at high incidence of preoperative nutritional risk, and those with an NRS-2002 score of > 3, history of alcohol consumption and surgical time of > 6 h have a higher risk of postoperative infections.