A comprehensive computational analysis to explore the importance of SIGLECs in HCC biology.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive, malignant cancer with a complex pathogenesis. However, effective therapeutic targets and prognostic biomarkers are limited. Sorafenib provides delaying cancer progression and survival improvement in advanced HCC. But despite 10 years of research on the clinical application of sorafenib, predictive markers for its therapeutic effect are lacking. METHODS: The clinical significance and molecular functions of SIGLEC family members were assessed by a comprehensive bioinformatic analysis. The datasets included in this study (ICGC-LIRI-JP, GSE22058 and GSE14520) are mainly based on patients with HBV infections or HBV-related liver cirrhosis. The TCGA, GEO, and HCCDB databases were used to explore the expression of SIGLEC family genes in HCC. The Kaplan-Meier Plotter database was used to evaluate relationships between the expression levels of SIGLEC family genes and prognosis. Associations between differentially expressed genes in the SIGLEC family and tumour-associated immune cells were evaluated using TIMER. RESULTS: The mRNA levels of most SIGLEC family genes were significantly lower in HCC than in normal tissues. Low protein and mRNA expression levels of SIGLECs were strongly correlated with tumour grade and clinical cancer stage in patients with HCC. Tumour-related SIGLEC family genes were associated with tumour immune infiltrating cells. High SIGLEC expression was significantly related to a better prognosis in patients with advanced HCC treated with sorafenib. CONCLUSIONS: SIGLEC family genes have potential prognostic value in HCC and may contribute to the regulation of cancer progression and immune cell infiltration. More importantly, our results revealed that SIGLEC family gene expression may be used as a prognostic marker for HCC patients treated with sorafenib.

Effect of depression disorder on the efficacy and quality of life of first-line chemotherapy combined with immunotherapy in oncogene-driver negative NSCLC patients.

Objective: The current research was to assess the relevance between depression disorder and first-line chemotherapy combined with immunotherapy, quality of life in patients with oncogene-driver negative non-small cell cancer (NSCLC). Methods: NSCLC patients (33 with depression disorder and 34 with no depression disorder) who was received first-line chemotherapy combined with immunotherapy performed Zung Self-rating Depression Scale (SDS) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Results: The Progression-Free Survival (PFS) of depression disorder group survivors were lower than these of no depression disorder group survivors (HR, 0.352; 95% CI, 0.201-0.617; P<0.05). The statistical significant was revealed about the Objective Response Rate (ORR) and Disease Control Rate (DCR) in two groups (P<0.05). The quality of life scores of NSCLC patients in no depression disorder group was significantly higher after chemotherapy combined with immunotherapy, and manifested as 92.7 ± 28 vs. 76.3 ± 23.3 (t=8.317, P<0.05), and had a significant difference. Conclusion: Depression disorder in oncogene-driver negative NSCLC patients influence the curative effect of chemotherapy combined with immunotherapy, and depression disorder was significantly negatively associated with quality of life following chemotherapy combined with immunotherapy.

The Impact of VR-CALM Intervention Based on VR on Psychological Distress and Symptom Management in Breast Cancer Survivors.

Objective: To evaluate the effectiveness and feasibility of Managing Cancer and Living Meaningfully based on VR (VR-CALM), which is used to manage expected symptoms of cancer itself, relieve psychological distress, and improve quality of life (QOL) in the Chinese breast cancer survivors (BCs). Methods: Ninety-eight patients with breast cancer were recruited in this study. These patients were randomly assigned to the VR-CALM group or the care as usual (CAU) group. All patients were evaluated by the Functional Assessment of Cancer Therapy-Breast cancer patient (FACT-B), Distress Thermometer (DT), Concerns About Recurrence Scale (CARS), Piper Fatigue Scale (PFS), Pittsburgh Sleep Quality Index (PSQI), The Self-Rating Anxiety Scale (SAS), and The Self-Rating Depression Scale (SDS) before and after VR-CALM or CAU application to BCs. We compared the differences in all these scores between the VR-CALM group and the control group. Results: Patients in the VR-CALM group showed a significant decrease in levels of distress, anxiety, depression, sleep disorders, and fatigue (t = -6.829, t = -5.819, t = -2.094, t = -3.031, t = -10.082, P ≤ 0.001, 0.001, 0.05, 0.01, 0.001, respectively) and had higher level of quality of life (t = 8.216, P ≤ 0.001) compared with the CAU group after intervention. And postintervention patients in VR-CALM group compared with preintervention showed lower level of distress and remarkable improvement of QOL (t = 11.521, t = -10.379, P ≤ 0.001, 0.001). The preintervention questionnaire revealed no significant between-group differences regarding distress, anxiety, depression, sleep disorders, fatigue, and quality of life. Conclusion: VR-CALM is a psychotherapy tailored to the needs of patients with breast cancer. This research innovatively used VR-based CALM intervention to improve psychological and chronic symptoms in BCs. The results of the present study indicate that VR-CALM has salutary effects on the improvement of QOL and relieves psychological distress, anxiety, depression, sleep disorders, and fatigue in BCs.

Depression in breast cancer patients: Immunopathogenesis and immunotherapy.

Depression is a common and recurrent mental illness with a complicated etiology, but the specific pathogenesis is not clear. Breast cancer increases susceptibility to depression, which leads to a poor prognosis. Rapid advances in the understanding of tumor immunology and neuroimmunology have provided new evidence for the pathogenesis of depression. Dysfunction of immune cells and cytokines cause depression by affecting tryptophan metabolism, serotonin levels, and blood-brain barrier permeability. Dysregulation of cytokines or intestinal flora may be shared between patients with depression and breast cancer. This review presents an overview of immune dysregulation in breast cancer patients with depression and proposes future alternative research directions and interventions.

Negative correlations of psychological distress with quality of life and immunotherapy efficacy in patients with advanced NSCLC.

To evaluate the relationships between psychological distress and immunotherapy efficacy, adverse reactions and quality of life scores in patients with advanced non-small cell lung cancer (NSCLC). A total of 104 NSCLC patients who received 4-6 cycles of standard immunotherapy were enrolled and evaluated with the Distress Thermometer (DT) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The aim was to analyze the correlation between psychological distress and quality of life and to analyze whether psychological distress affects the efficacy of and adverse reactions to immunotherapy. The objective response rate (ORR) and disease control rate (DCR) of the psychological distress group were 6% and 50%, respectively, and those of the no psychological distress group were 18.5% and 83.3%, respectively. The differences were statistically significant (χ2=14.131, P<0.05). The progression-free survival (PFS) of advanced NSCLC patients who received comprehensive immunotherapy and had no psychological distress was significantly better than that of the psychological distress group (HR, 0.338; 95% CI, 0.192-0.592; P<0.05). The PFS of advanced NSCLC patients who received immunotherapy combined with chemotherapy in the no psychological distress group was significantly better than that in the psychological distress group (HR, 0.458; 95% CI, 0.296-0.709; P<0.05). Psychological distress in advanced NSCLC patients affects the efficacy of immunotherapy, and psychological distress is negatively correlated with quality of life during immunotherapy.

Exploring ALDH2 expression and immune infiltration in HNSC and its correlation of prognosis with gender or alcohol intake.

The aldehyde dehydrogenase 2 point mutation (ALDH2*2) is a common frequent human gene variant, especially in East Asians. However, the expression and mechanism of action of ALDH2 in HNSC remain unknown. The present study explored the clinical significance and immune characteristics of ALDH2 in HNSC. The receiver operating characteristic curve was analysed to assess the diagnostic value of ALDH2 expression. ALDH2 expression in normal tissues and HNSC tissues was evaluated by IHC, and we also analysed ALDH2 gene expression in 4 HNSC cell lines. ALDH2 expression was significantly reduced in HNSC tissues compared to normal tissues (p < 0.05). HNSC patients with high ALDH2 expression had a better prognosis compared to patients with low ALDH2 expression (p < 0.05). GSEA indicated that these gene sets were correlated with signalling pathways, including the JAK-STAT signalling pathway. Unexpectedly, we found a significant prognostic effect of ALDH2 for HNSC based on alcohol consumption and the male sex. The correlation between ALDH2 expression and immune inhibitors showed an effect for ALDH2 in modifying tumour immunology in HNSC, and there may be a possible mechanism by which ALDH2 regulates the functions of T cells in HNSC. In addition, we developed a prognostic nomogram for HNSC patients, which suggested that low ALDH2 expression indicated poor prognosis in HNSC patients who were males and alcoholics.

Comprehensive Analysis of Aldehyde Dehydrogenases (ALDHs) and Its Significant Role in Hepatocellular Carcinoma.

Oxidative DNA damage is closely related to the occurrence and progression of cancer. Oxidative stress plays an important role in alcohol-induced hepatocellular carcinoma (HCC). Aldehyde dehydrogenase (ALDH) is a family of enzymes that plays an essential role in the reducing oxidative damage. However, how ALDHs family affects alcohol-related HCC remains obscure. We aimed to explore the correlation between the differential expression of ALDHs in patients with HCC and pathological features, as well as the relationship between ALDHs and prognosis, and finally analyze the possible mechanism of ALDHs in targeted therapy of HCC. The data of HCC were downloaded from The Cancer Genome Atlas (TCGA) database. This research explored the expression and prognostic values of ALDHs in HCC using Oncomine, UALCAN, Human Protein Atlas, cBioPortal, Kaplan-Meier plotter, GeneMANIA, Tumor Immune Estimation Resource, GEPIA databases, and WebGestalt. Low mRNA and protein expressions of ALDHs were found to be significantly associated with tumor grade and clinical cancer stages in HCC patients. In particular, the loss of ALDH expression is more obvious in Asians, and its effect on prognosis is far more significant than that in the White race. Our findings play an important role in the study of prognostic markers and anti-liver cancer therapeutic targets for the members of the ALDHs family, especially in patients with liver cancer in Asia.

ALDH2 is a prognostic biomarker and related with immune infiltrates in HCC.

Hepatocellular carcinoma is a malignant type of carcinoma with complicated pathogenesis. For HCC patients, there is not only a lack of valuable therapeutic targets, but also a lack of prognostic biomarker. The protein encoded by Aldehyde Dehydrogenase 2 Family Member (ALDH2) is a critical member of the aldehyde dehydrogenase family. Many researchers have found that ALDH2 mutations play an important role in the activation of hepatocellular carcinoma carcinogenic pathways. However, the clinicopathological meaning of ALDH2 in HCC and its relation with immune infiltration is still indistinguishable. In this study, we explored the expression of ALDH2 in 41 HCC tissues by immunohistochemistry. The clinicopathological meaning and molecular function of ALDH2 were analyzed and evaluated through comprehensive bioinformatics. ALDH2 expression in HCC was validated in TCGA, GEO and Oncomine databases, and a survival of ALDH2 based on TCGA database was analysed. LinkedOmics was used to classify the co-expressed genes of ALDH2 and its regulatory factors. The relation between ALDH2 and immune infiltration in HCC was further explored by TIMER. IHC results showed decreased levels of ALDH2 in HCC tumor tissues compared with corresponding normal liver tissues. The pathological grade and prognosis of patients with low expression of the ALDH2 gene were worse. Bioinformatics analysis results showed that ALDH2 was considerably down-regulated in cancer tissues compared with corresponding normal liver tissues in 8 GEO series and TCGA profile (all P<0.05). A nomogram was designed using expression of ALDH2 and clinical factors. ALDH2 was correlated with dendritic cells and macrophages in immune infiltration. In conclusion, ALDH2 has significant prognostic value in hepatocellular carcinoma and they may play key roles in regulating tumor progression and the immune cells infiltration. Our results suggest that ALDH2 may be a new type of tumor biomarker, which can be used to judge the prognosis, targeted therapy and immunotherapy of patients with HCC.

Changes in cytokine levels in breast cancer patients with CRCI before or after CALM intervention.

To investigate the changes in cytokine (interleukin 1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α) and interleukin 4 (IL-4)) levels and cognitive function before and after managing cancer and living meaningfully (CALM) intervention, in early-stage breast cancer patients with chemotherapy-related cognitive impairment (CRCI). One hundred and twenty-eight breast cancer patients with CRCI enrolled in this study, there are fifty patients underwent with 6 CALM interventions and seventy-eight patient care as usual (CAU). Cytokine (IL-1ß, TNF-α and IL-4) levels in the patients were assessed, and the patients were evaluated with the Mini-Mental State Examination (MMSE), Prospective Memory (PM) and Retrospective Memory (RM), and Quality-of-life (QOL) and Psychological Distress Thermometer (DT) assessments before CALM intervention (BCM), after CALM intervention (ACM) and care of usual (CAU). Measures at these two time points and two groups were compared. There were significant differences in the performance on the RM, PM, MMSE, QOL and DT measures after, compared to before (t=8.126, t=8.007, t=-10.789, t=9.236, t=17.649, respectively; P<0.05), the CALM intervention, compared to CAU (t=-7.408, t=-7.300, t=8.128, t=-8.851, t=-10.572, respectively; P<0.05). In addition, cytokine levels, including IL-1ß, TNF-α and IL-4, were significantly different before and after the CALM intervention (t=5.073, t=4.228, t=5.815, respectively; P<0.05) and the two groups (ACM vs CAU) were distinctly different (t=-3.353, t=-2.694, t=-3.268, respectively; P<0.05). furthermore, the cytokine levels (IL-1ß, TNF-α and IL-4) have linear correlation with cognitive function before and after CALM intervention (r=-0.343/r=0.538, r=-0.375/r=-0.330, r=-0.310/r=-0.541, respectively; P<0.05). The present results indicated that CALM intervention could alleviate CRCI and that this process is accompanied by changes in IL-1ß, TNF-α and IL-4 levels. These results further confirm that cytokines may be involved in CRCI and that CALM may become an efficient method to relieve CRCI-related symptoms in breast cancer patients.

Changes in plasma IL-1ß, TNF-α and IL-4 levels are involved in chemotherapy-related cognitive impairment in early-stage breast cancer patients.

To investigate changes in cytokine (IL-1ß, TNF-α and IL-4) levels before and after chemotherapy and their correlation with cognitive impairment in early-stage breast cancer (BC) patients, the 190 BC patients enrolled in this study were divided into two groups: a before chemotherapy group (BCG) and an after chemotherapy group (ACG). The BCG was also divided into two subgroups according to the cognitive assessment results: one group with normal cognition (CNG) and one group with impaired cognition (CIG). Plasma cytokine levels (IL-1ß, TNF-α, and IL-4) were evaluated in all patients. The mini-mental state examination (MMSE), prospective and retrospective memory questionnaire (PRMQ), and functional assessment of cancer therapy-cognitive function version 3 (FACT-Cog, version 3) were used to evaluate patients' self-perceived cognitive impairments. Furthermore, their quality of life (QOL) was evaluated. Plasma IL-1ß, TNF-α and IL-4 levels were higher in the ACG than in the BCG (Z = -3.089, -2.458 and -1.987; P = 0.002, 0.014, and 0.047; respectively). Moreover, plasma IL-1ß, TNF-α and IL-4 levels were higher in the CIG than in the CNG (Z = -4.353, -3.383 and -2.522; P = 0.000, 0.001 and 0.012; respectively). Furthermore, a correlation was noted between cognition (MMSE, retrospective memory (RM), prospective memory (PM), and FACT-Cog scores) and QOL in BC patients (r = -0.790, 0.852, 0.847 and 0.937, respectively), and a correlation was observed between cognition and cytokine levels (IL-1ß, TNF-α, and IL-4) in BC patients (r = -0.681, -0.572 and -0.626; respectively). The present results indicated that changes in cytokine levels may occur in BC patients with chemotherapy-related cognitive impairment (CRCI). We also found that CRCI was associated with QOL after chemotherapy in BC patients. This study provides a theoretical basis for the improvement of QOL in BC patients.

Managing Cancer and Living Meaningfully (CALM) Intervention on Chemotherapy-Related Cognitive Impairment in Breast Cancer Survivors.

Objective: To evaluate the effectiveness and feasibility of Managing Cancer and Living Meaningfully (CALM), which is used to reduce chemotherapy-related cognitive impairment (CRCI), relieve psychological distress, and improve quality of life (QOL) in Chinese breast cancer survivors (BCs). Methods: Seventy-four BCs were enrolled in this study. All patients were randomly assigned to either the CALM group or the care as usual (CAU) group. All patients were evaluated by the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), Distress Thermometer (DT), and the Functional Assessment of Cancer Therapy-Breast (FACT-B) before and after CALM or CAU application to BCs with CRCI. We compared the differences in all these scores between the CALM group and the control group and analyzed the correlation between cognitive function and QOL. Results: Compared with the CAU group, the performance of the CALM group on the FACT-Cog, DT, and FACT-B showed significant differences before and after CALM (t = -18.909, -5.180, -32.421, P = .000, .000, .000, respectively). Finally, there was a positive correlation between cognitive function and QOL in breast cancer patients before (r = 0.579, P = .000) and after (r = 0.797, P = .000) treatment. Conclusions: The present results indicated that CALM has salutary effects on the improvement of cognitive impairment and QOL and relieves psychological distress in breast cancer patients, which may be due to a positive correlation between psychological distress and cognitive function or QOL.