Objective To investigate the prognostic value of ERBB2 Exon20ins (Exon20ins) in advanced non-small cell lung cancer (NSCLC) patients receiving first-line chemotherapy combined with immunotherapy. Methods A retrospective analysis was conducted on clinical data from ERBB2-mutant stage IV NSCLC patients who received first-line chemotherapy combined with immunotherapy at West China Hospital of Sichuan University between 2020 and 2024. ERBB2 wild-type patients were matched using propensity score matching. Clinical pathological characteristics, distant metastatic sites, and treatment outcomes were compared among patients with different mutation statuses. The primary endpoint was progression-free survival (PFS), and Kaplan-Meier method was used to plot survival curves. Cox regression analysis was performed to adjust for confounding factors. Results This study included 41 ERBB2-mutant stage IV NSCLC patients, of whom 22 had Exon20ins mutations, and 19 had other ERBB2 mutations. Forty-one ERBB2 wild-type patients were matched for comparison. The mean age of all patients was 60.0±9.3 years, with 61 males (74.4%). A total of 67 patients (81.7%) received chemotherapy combined with immunotherapy, and 15 patients (18.3%) received chemotherapy combined with immunotherapy and anti-angiogenesis therapy. The Exon20ins group showed a higher incidence of lymph node metastasis compared with the ERBB2 other mutation group and the wild-type group (36.4% vs. 15.8% vs. 9.8%, P=0.045). The median PFS in the Exon20ins group was significantly shorter than in the other mutation group (5.8 months vs. 10.3 months, P=0.025) and the wild-type group (5.8 months vs. 8.3 months, P=0.023). Univariate Cox regression analysis indicated that the ERBB2 Exon20ins mutation was an adverse prognostic factor (Exon20ins vs. other ERBB2 mutations, HR=2.9, 95%CI 1.18 - 7.1, P=0.014; Exon20ins vs. wild-type, HR=2.6, 95%CI 1.25 - 5.6, P=0.014). The combination with anti-angiogenesis therapy did not significantly affect the prognosis of PFS (HR=0.66, 95%CI 0.28 - 1.6, P=0.363). Multivariate Cox regression analysis revealed that the ERBB2 Exon20ins mutation was an independent adverse prognostic factor for PFS (Exon20ins vs. other ERBB2 mutations, HR=3.3, 95%CI 1.27 - 8.3, P=0.015; Exon20ins vs. wild-type, HR=2.7, 95%CI 1.2 - 5.88, P=0.014). For the 67 patients receiving chemotherapy combined with immunotherapy, Cox regression analysis showed that the ERBB2 Exon20ins mutation was still associated with poor prognosis in advanced NSCLC (Exon20ins vs. other ERBB2 mutations, HR=3.2, 95%CI 1.12 - 9.1, P=0.030; Exon20ins vs. wild-type, HR=2.5, 95%CI 1 - 5.88, P=0.040). Conclusions Advanced NSCLC patients with ERBB2 Exon20ins mutation have a worse prognosis compared with those with other ERBB2 mutation subtypes or ERBB2 wild-type when treated with first-line chemotherapy combined with immunotherapy. This suggests that ERBB2 Exon20ins mutation, as a particularly refractory mutation, requires the exploration of new combination strategies based on molecular subtyping to improve survival outcomes.
Objective To summarize the research progress of alternative splicing in pancreatic cancer, and to provide reference for further research. MethodThe experimental and clinical studies of alternative splicing in pancreatic cancer were reviewed.Results Alternative splicing dysregulation resulted in changed gene expression or novel isoform formation, thereby influencing the carcinogenesis, progression or chemoresistance of pancreatic cancer. The differentially expressed alternative splicing isoforms may serve as diagnostic markers, indicators of aggressiveness or prognostic markers of pancreatic cancer. Conclusion Further investigation of the molecular mechanisms of alternative splicing in carcinogenesis and progression of pancreatic cancer is a new way to improve the early diagnosis and treatment of pancreatic cancer.
ObjectiveTo detect level of circulating tumor cells (CTCs) in peripheral venous blood of fasting patients with gastric cancer (GC) and to analyze relationships between CTCs and clinicopathologic features and prognosis of patients with GC.MethodsOne hundred patients with GC were selected (GC group), who underwent the surgery and confirmed by the histopathology in the 940 Hospital of Joint Service of PLA, from August 2015 to December 2016. Thirty-eight patients with gastric benign lesions who were treated in this hospital at the same time were selected as the control group. The 7 mL peripheral venous blood of the elbow in the morning was taken from the fasting patients and the CTCs were detected by the immunomagnetic microparticle negative enrichment combined with immunofluorescence in situ hybridization within 24 h. The positive rate of CTCs was calculated and its relationships with the clinicopathologic features (tumor location, tumor invasion depth, degree of differentiation, TNM stage, lymph node metastasis, and vascular tumor thrombus) and the progression-free survival of the patients with GC were analyzed.ResultsThe positive rate of peripheral venous blood CTCs in the GC group was 89.0% (89/100), which was higher than that in the control group (10.5%, 4/38), and the difference was statistically significant (P<0.001). The levels of CTCs in the patients with GC were significantly correlated with the tumor invasion depth (P=0.017), lymph node metastasis (P=0.038), and TNM stage (P=0.016), which were not associated with the age, gender, tumor location, degree of differentiation, and vascular tumor thrombus (P>0.050). The predictive value of CTCs for the diagnosis of GC was significantly superior to that of the tumor markers CEA, CA19-9, or CA125. The progression-free survival of patients with low CTCs expression was significantly longer than that in the patients with high CTCs expression (χ2=5.172, P=0.023).ConclusionsDetecting CTCs of patients with GC by immunomagnetic particle negative enrichment combined with immunofluorescence in situ hybridization has a high sensitivity. And it can improve early diagnosis of patients with GC. Preoperative CTCs detection has a certain value in guiding staging of GC and predicting prognosis of patients with GC.
ObjectiveTo explore the significance of continuous surveillance of anti-endothelial cell antibody (AECA) in patients with chronic obstructive pulmonary disease (COPD) in one year.MethodsThirty-six patients with acute exacerbation of COPD and 93 patients with stable COPD were selected from Guizhou Provincial People's Hospital from October 2019 to February 2020, thirty healthy people in the same period were selected as normal control group. In the stable phase group, >386.17 pg/mL was included in the higher group, and <386.17 pg/mL was included in the lower group according to the AECA median (386.17 pg/mL). According to the grouping criteria, the patient with the AECA median was omitted, the sample size of AECA higher group and lower group accounted for 46 cases, respectively. AECA test, lung function examination, the number of acute exacerbations in the past 1 year and MMRC score were performed for each group; At the same time, all the above contents were followed up dynamically.Results1. Comparison of AECA levels among the three groups: the acute exacerbation COPD group was higher than the stable phase group and the normal control group, and the stable phase group was higher than the normal control group, with statistical significance (all P<0.05). 2. Overall comparison of related indicators before and after follow-up in COPD stable period group: AECA level was higher than baseline after follow-up, and the follow-up after 12 months was higher than that after 6 months; After 12 months, forced expiratory volume in one second (FEV1), the ratio of FEV1 to forced vital capacity (FVC), and FEV1%pred were all lower than baseline, and the first two indexes were lower than those after 6 months follow-up. The number of acute exacerbations and mMRC score after 12 months were higher than that after 6 months follow-up, with statistical significance (all P<0.05). 3. Comparison of related indicators after follow-up between the higher and lower AECA groups: Follow-up after 12 months showed that AECA, the number of acute exacerbations and mMRC score in the higher AECA group were all higher than those in the lower AECA group at the same period, and the number of acute exacerbations and MMRC score in the higher AECA group were higher than those in the lower AECA group at 6-month follow-up. The FEV1, FEV1%pred and FEV1/FVC of the higher AECA group followed up after 12 months were lower than those of the lower AECA group at the same period, and the FEV1 and FEV1%pred of the higher AECA group followed up after 6 months were lower than those of the lower AECA group at the same period, and all the differences were statistically significant (all P<0.05).ConclusionAbnormality of AECA expression in COPD may be associated with continued decline in lung function, number of acute exacerbations in the previous 1 year, and increased mMRC score, and therefore may be associated with continued progression.
Objective To analyze the aortic development in patients with mild coarctation of the aorta (CoA) and ventricular septal defect (VSD) after isolated VSD repair and to explore the risk factors affecting postoperative aortic development. Methods A retrospective analysis was conducted on the clinical data of 4231 patients who underwent VSD repair at Guangdong Provincial People’s Hospital from January 2018 to August 2023. Patients with mild CoA were selected as the study subjects. Based on whether CoA progressed postoperatively, patients were divided into a progression group and a non-progression group. Univariate and multivariate analyses were performed, and a logistic regression model was established to analyze the factors affecting postoperative aortic development. Results A total of 231 patients were included, with 142 males and 89 females, and a median age of 223 (105, 635) days. Among the 231 patients, 30 showed varying degrees of mild CoA progression during postoperative follow-up, with an incidence rate of 13.0%. Multivariate logistic regression analysis revealed that higher preoperative pulmonary artery pressure [OR=2.053, 95%CI (1.095, 3.850), P=0.025] and larger VSD [OR=20.200, 95%CI (1.614, 254.440), P=0.020] were risk factors for postoperative CoA progression. Conclusion Most patients with mild CoA and VSD exhibited varying degrees of catch-up growth in the aorta postoperatively. Higher preoperative pulmonary artery pressure and larger VSD size are influencing factors for postoperative CoA progression, necessitating more cautious surgical strategies and closer follow-up for this subset of patients.
Objective To explore the relationship between immune state and disease progression or severity of patients with hepatitis B virus (HBV). Methods A total of 332 patients infected with HBV diagnosed and treated from January 2012 to December 2013 were divided into acute hepatitis B (AHB) group (n=25), chronic hepatitis B (CHB) group (n=237) and cirrhosis group (n=70) according to disease progression. Moreover, CHB group was divided into mild (n=24), moderate (n=103), serious (n=72) and severe group (liver failure group,n=38) according to disease severity, while cirrhosis group was divided into hepatocellular carcinoma (HCC) group (n=13) and non-HCC group (n=57). The immune indexes including immunoglobulin (Ig), complement (C) and T-lymphocyte subsets were tested and compared. Results The immune indexes were not significantly different between AHB group and CHB group (P>0.05). Compared with AHB group and CHB group, cirrhosis group had higher levels of IgG and IgA, and lower levels of CD3+, CD4+ and CD8+ T cells count (P<0.05). Compared with non-HCC group, HCC group had more male patients without antiviral therapy, who had higher levels of C3 and C4 (P<0.05). As disease progressed, the levels of alanine fcell couaminotransferase, aspartate aminotransferase, total cholesterol, Fibroscan index, IgG, and IgA of CHB patients all gradually increased, while the levels of C3 and C4 and the counts of CD3+ and CD4+ T cells gradually declined. Conclusions The immune state of patients infected with HBV has a certain relationship with disease progression or severity, and immunoglobulin, complement and T cells count can partly reflect the severity of the disease. Cirrhosis patients accompanied with high levels of C3 and C4 should pay high attention to antiviral therapy and be vigilant on HCC.
Objective To summarize the relation between various kinds of immune cells infiltration in tumor microenvironment and prognosis of hepatocellular carcinoma (HCC). Method Literatures on the relation between immune cell infiltration in tumor microenvironment and prognosis of HCC in recent years were collected and reviewed. Results The immune cell infiltration in the tumor microenvironment of HCC was inextricably linked with the progression of HCC. CD4+ T cells, CD8+ T cells, M1 macrophages, B cells, and memory T cells might be associated with a good prognosis in patients with HCC, while regulatory T cells, regulatory B cells, and M2 macrophages might be related to the poor prognosis of patients with HCC. Conclusion The study of immune cell infiltration in HCC can provide new ideas for precise immunotherapy of HCC.
Objective To summarize the role of exosomal proteins in the occurrence, development, and diagnosis and treatment of pancreatic cancer, providing a reference for the exploration of biomarkers and therapeutic targets in this field. MethodA systematic review of recent domestic and international literature on the mechanisms of exosomes and their proteins in pancreatic cancer was conducted. ResultsProteins carried by tumor-derived exosomes, such as galectin-3 binding protein, V-set andimmunoglobulin domain containing 2, Zrt- and Irt-like protein 4, aspartate aminotransferase 1, could effectively regulate the tumor microenvironment and influence the cell behavior, playing an important role in the occurrence, progression, and metastasis of pancreatic cancer. Additionally, exosomal proteins could serve as potential biomarkers for the early diagnosis of pancreatic cancer. For example, exosomal membrane proteins DNAJ heat shock protein family (HSP40) member B11, and glypican 1 were highly expressed in pancreatic cancer tissues, indicating their potential. ConclusionExosomal proteins are expected to become novel biomarkers and intervention targets for the early diagnosis and targeted therapy of pancreatic cancer, providing new ideas for improving the diagnosis and treatment of pancreatic cancer.
ObjectiveTo study the effect of tumor associated neutrophil (TAN) releasing a proliferation-inducing ligand (APRIL) on the proliferation of pancreatic cancer cells in microenvironment.Methods① The expressions of APRIL in neutrophils (differentiated by HL-60 cell) and TAN cells were detected by use ELISA. ② The expressions of APRIL receptors B cell maturation antigen (BCMA) and trans-membrane activator and CAML interactor (TACI) in pancreatic cancer cell line PANC-1 were confirmed by use Western blotting. ③ Pancreatic cancer PANC-1 cells were co-cultured with TAN, and divided into a PANC-1 control group (referred to as the control group), a PANC-1+TAN treatment group (referred to as the PANC-1+TAN group), PANC-1+TAN+APRIL antibody treatment group (referred to as PANC-1+TAN+APRIL group), and PANC-1+rtificial recombinant APRIL protein (rAPRIL) treatment group (referred to as PANC-1+rAPRIL group). The CCK8 method was used to determine TAN release of APRIL on PANC-1 effect of cell proliferation activity.Results① The APRIL content in the culture medium of TAN cell group was higher than that of neutrophil group [(556.20±84.38) pg/mL vs. (377.17±57.07) pg/mL, P=0.038]. ② PANC-1 cells express the receptors BCMA and TACI of APRIL. ③ PANC-1 cell activity of PANC-1+TAN group and PANC-1+rAPRIL group [(126.80±1.42)%, (168.95±12.54)%] were significantly higher than the control group [(100 ± 0.00)%, P<0.05, P<0.001], the activity of PANC-1 cells in the PANC-1+TAN group was significantly higher than that in the PANC-1+TAN+APRIL group [(86.29 ± 12.20)%, P=0.003] and significantly lower than that of PANC-1+rAPRIL group (P=0.002), the activity of PANC-1 cells in PANC-1+rAPRIL group was significantly higher than that in PANC-1+TAN+APRIL antibody group (P<0.001).ConclusionIn the microenvironment of pancreatic cancer, the release of APRIL from TAN increases, which promotes the proliferative activity of PANC-1 in pancreatic cancer cells, which provides a new idea for the mechanism research and treatment of pancreatic cancer progression.
Cancer is a disease that incidence rate, disability rate and mortality rate are high all over the world. It brings great physical and mental pain to patients. Cancer patients are in a life-threatening state of disease for a long time, which will produce fear of progression (FoP). FoP is a psychological state in which fear of disease may recur or progress. As early as the 1980s, foreign countries began the psychological research on the FoP of cancer patients. They found that this fear really exists in cancer patients and is affected by many factors. This paper reviews the concept of FoP and the related factors affecting FoP in cancer patients. The purpose is to provide reference for clinical early evaluation and reducing the FoP of cancer patients and formulating corresponding nursing measures.