Background and Purpose Gut microbes play an important role in the occurrence of lung cancer, immunotherapy, and chemotherapy. In this study, we analyzed the characteristics of gut microbes in patients with lung cancer and investigated the effect of gut microbes on anti‐PD‐1 therapy combined with chemotherapy. Methods Fecal samples from 21 non‐small cell lung cancer (NSCLC) patients and 22 healthy volunteers who were treated in the Fourth Hospital of Hebei Medical University from 2019 to 2021 were collected. DNA was extracted from all samples, and the V3‐V4 region of the bacterial 16S rRNA gene was PCR‐amplified using the Illumina sequencing platform, and R language was used for data analysis. Results There were significant differences in the Beta diversity and metabolic pathways of gut microbes between NSCLC patients and healthy individuals (p < 0.05). Bifidobacterium, Escherichia, and Sarterella were significantly enriched in patients with clinical benefit response (p < 0.05), and these three bacteria had certain predictive value for clinical benefit. Patients with Bifidobacterium breve had significantly longer median progression‐free survival (mPFS) compared with patients with no detectable Bifidobacterium breve feces at baseline (106 days vs. NR, p < 0.001). Multivariate COX analysis showed that the presence of B.breve was an independent good prognostic factor affecting the PFS of patients receiving combination therapy (p < 0.05). Conclusion The clinical efficacy of anti‐PD‐1 therapy combined with chemotherapy in Chinese advanced NSCLC patients is closely related to the gut microbiota, and Bifidobacterium breve may be a potential biomarker to predict the efficacy of immune‐combined chemotherapy.
e21005 Background: The gut microbiome has been demonstrated to be closely related to not only the occurrence of lung cancer but also its anti-PD-1 based immunotherapy and chemotherapy. There is little characteristic analysis of gut microbiota in Chinese lung cancer patients, and the impact of gut microbiota on combined anti-PD-1 treatment and chemotherapy remains unclear. Methods: Fecal samples from 22 healthy volunteers and advanced-NSCLC 21 patients who were treated in the Fourth Hospital of Hebei Medical University from 2019 to 2021 before and after anti-PD-1 treatment combined with chemotherapy were collected. DNA was extracted from all samples, and the V3-V4 region of the bacterial 16S rRNA gene was PCR-amplified using the Illumina sequencing platform. The study results were analyzed using bioinformatic data. Results: The composition of gut microbes in NSCLC patients and healthy people at the phylum level was roughly similar, with Firmicutes as the main phylum. However, there were significant differences in Beta diversity (P<0.05). The bray_curtis principal coordinate analysis revealed a significant difference in the microbiota between patients before and after combined treatment (P<0.05). According to the RECIST 1.1 criteria, the efficacy of the combination therapy was evaluated. The patients with complete remission, partial remission, or stable efficacy after 6 cycles were the clinical benefit response group (CBR, n=10), and the patients with disease progression in the efficacy evaluation were the non-clinical benefit group (NCB, n=8). The results suggested that the CBR group was enriched in Bifidobacterium_longum, Bifidobacterium_adolescentis, Bifidobacterium_bifidum, and Bifidobacterium_breve at the species level (P<0.05) compared with the NCB group. Compared with the median progression-free survival (mPFS) of patients without Bifidobacterium_breve at baseline, the mPFS of patients with the kind of gut bacteria was significantly prolonged (P<0.001).Specifically, mPFS without Bifidobacterium_breve group was 106 days (95% CI: 37-175), mPFS of the Bifidobacterium_breve group was Not Reached (95% CI: NC-NC). Conclusions: The clinical response of combined anti-PD-1 treatment and chemotherapy in advanced NSCLC patients was closely associated with the gut microbiome,and Bifidobacterium_breve may be effective biomarkers to predict the survival benefit of NSCLC combined therapy, which provided new therapeutic targets for modulating the response to cancer therapy.
Background: The prognosis of older patients with ovarian cancer is poor. We evaluated the effect of chronological age and different treatment characteristics on the prognosis of older patients with ovarian cancer; Methods: The study retrospectively analyzed patients aged over 60 years who underwent cytoreduction followed by platinum-based adjuvant chemotherapy between January 2011 and December 2019 in two national centers in China. Propensity score matching (PSM, 1:1) was performed to stratify the comorbidity- and treatment-related factors. The Kaplan–Meier method was employed to estimate progression-free survival (PFS) in the original cohort and the cohort after PSM; Results: A total of 324 patients were evaluated. The Age ≥ 70 group often received more neoadjuvant chemotherapy (62.3% vs. 31.2%, p < 0.001), more discontinuation of adjuvant chemotherapy (31.2% vs. 10.8%, p < 0.001), and had more severe chemotherapy-related toxicity (45.6% vs. 34.2%, p = 0.040) than the Age < 70 group. After matching, the PFS of the Age < 70 group was not significantly different from the Age ≥ 70 group (median PFS = 12.4 and 11.9 months, respectively, p = 0.850). Furthermore, the advanced FIGO stage, non-R0 cytoreduction, and discontinuation of adjuvant chemotherapy were all found to be poor prognostic factors. Serum albumin level <40 g/L (HR = 2.441, p = 0.018) and age ≥ 70 years (HR = 2.639, p = 0.008) led to more severe chemotherapy-related toxicity. Additionally, poor renal function (HR = 5.128, p = 0.002) was in association with discontinuation of adjuvant chemotherapy; Conclusions: The chronological age of older patients cannot be seen as a poor prognostic factor. Older patients may benefit most from R0 cytoreduction followed by the completion of chemotherapy. Postoperative poor renal function and serum albumin level <40 g/L may help predict the discontinuation of adjuvant chemotherapy.
e15533 Background: Our previous study have found that TRIM29 expressed higher in right colon cancer than left colon cancer and rectal cancer.But the main functions of TRIM29 was not fully clarified.Bioinformatics can be used for exploring the biological function of a gene.So we further explored the molecular mechanism by using bioinformatics analysis.The results showed that TRIM29 correlated to immune dysfunction.Mismatch repair deficient(dMMR) is closely related to the efficacy of immunotherapy in colorectal cancer.We also used GEO data to explore the relationship between TRIM29 and dMMR.At last, clinical pathological data were used to explore the relationship between TRIM29 and tumor lymphocyte infiltration. Methods: At first, bioinformatics analysis was used to further explore the molecular mechanism of TRIM29.Hub genes correlated with TRIM29 and Reactome/KEGG Pathway of the hub genes were identified and performed using String database(http://string.embl.de/).TISIDB(http://cis.hku.hk/TISIDB/) was utilized to analyse the correlations between TRIM29 expression and tumor infiltrating lymphocytes, immunomodulator and chemokine.Then GEO public data including 583 sample size was download and used to confirm the correlation ship between TRIM29 expressed and pMMR/dMMR status.At last, HE sections of the 227 CRC patients were collected to explore the connection between TRIM29 and tumor infiltrating lymphocytes. Results: Functional annotations and immune activity analysis showed TRIM29 is related to tumor infiltrating lymphocytes and due to immune dysfunction in colorectal patients.For tumor infiltrating lymphocytes analyzing, elevated TRIM29 was significantly associated with Act_DC, iDC,monocyte, NK,NKT, pDC, Tcm_CD4, Tcm_CD8, Tem_CD8 and Th1 cell infltration in colorectal ( P< 0.05), leading to a general increase in immune infiltration.For chemokines analyzing,elevated TRIM29 was significantly associated with high expression of CXCR1,CXCR2 and CXCR4( P< 0.05).For immunostimulators analyzing,TRIM29 over-expression was significantly associated with C10orf54, CD70, CD276, HHLA2 and ICOSLG, causing immune imbalance( P< 0.05).For immunoinhibitors analyzing, elevated TRIM29 expression was significantly associated with PD-L1, LGALS9, PD-1, PVRL2,TGFBR1,TIGIT and VTCN1( P< 0.05).The HE results revealed that high TRIM29 protein expression was correlated with high tumor-infiltrating lymphocytes ( P= 0.0053).GSE39582 data analyzing results showed that dMMR patients expressed higher TRIM29 level than dMMR patients( P= 0.0014). Conclusions: High TRIM29 expression is related to tumor infiltrating lymphocytes and due to immune dysfunction in colorectal patients.Elevated TRIM29 expression up regulating immune checkpoint molecules after immune stimulation to avoid immune damage.TRIM29 may serve as a new biomarker for immunotherapy.
e16049 Background: Esophageal squamous cell carcinoma (ESCC) is a common malignancy without effective therapy. Previous studies have shown that chemotherapy and immunotherapy is affected by esophageal microbiome. The effect of esophageal microbiota on the efficacy of chemotherapy and immunotherapy for ESCC remain poorly understood. Methods: DNA was extracted from blood, oral mucosal, saliva, urine, fecal samples from 14 ESCC patients after chemotherapy and 18 ESCC patients after immunotherapy. Total microbial genomic DNA samples were extracted using an OMEGA Soil DNA Kit (D5625-01). The V3–V4 regions of bacterial 16S rRNA genes were amplified by PCR using the forward primer and the reverse primer and were sequenced with Illumina MiSeq platform. In order to comprehensively evaluate the α diversity of microbial communities, we used Chao1 and Observed Species indices to characterize the richness, Shannon and Simpson indices to characterize the diversity. PCoA were used to analyze differences in β diversity. Functions of 16S rRNA sequences were predicted using the PICRUSt2 and KEGG databases. Results: The α diversity in patients with ESCC after immunotherapy were higher than those in patients with ESCC after chemotherapy. There was a statistically significant difference in β diversities between ESCC patients after chemotherapy and ESCC patients after immunotherapy. In terms of the microbial functions in ESCC patients after chemotherapy and immunotherapy, the metabolic pathways accounted for the most. Conclusions: This study is conducive to exploring new mechanisms for tumor cells to evade host immune surveillance, providing new ideas and new strategies for the microecology-based therapy of ESCC.
e24132 Background: Patients with cancer experience different degrees of loss of dignity. Exploring the characteristics of dignity loss for patients with cancer is rare in China, but it is of great significance for patients and their families in the whole anti-cancer trajectory. Methods: Inpatients and outpatients with cancer from the Fourth Hospital of Hebei Medical University were enrolled in this study. The Patient Dignity Inventory(PDI) and EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) was used for measuring patients’ dignity loss and quality of life. Spearman’s correlation analysis was conducted to analyze the correlation factors of dignity loss, and the correlation among dignity loss, quality of life and its dimensions. Results: A total of 403 patients with cancers were included in this study. In terms of loss of dignity, 20 patients (4.96%) didn’t report loss of dignity, 295 patients (73.20%) had mild loss of dignity, 78 (19.35%) had moderate and 10(2.48%) had severe loss of dignity. The three most prevalent PDI problems of patients were “experiencing physically distressing symptoms”(146, 36.23%), “Feeling that I am a burden to others” (126,31.27%) and “worrying about future” (114, 28.29%) . Companionship(r = 0.167, P = 0.001), PS(r = 0.392, P < 0.001), diagnosis to investigation time (r = 0.107, P = 0.031), stage of disease (r = 0.279, P < 0.001), stage of treatment (r = 0.333, P < 0.001), surgery and recurrence (r = 0.158, P = 0.001), anxiety (r = 0.612, P < 0.001), depression (r = 0.603, P < 0.001), psychological distress (r = 0.453, P < 0.001), symptom burden (r = 0.421, P < 0.001) and impact on life (r = 0.450, P < 0.001) were positive correlated with loss of dignity. Age (r = -0.134, P = 0.007), occupation (r = -0.124, P = 0.013) were negative correlated with loss of dignity. Loss of dignity and quality of life are significant correlated with each other. Dignity existential distress showed moderate negative correlation with emotional function (r = -0.513, P < 0.001). Dignity symptom distress showed moderate negative correlation with emotional function (r = -0.675, P < 0.001) and social function (r = -0.515,P < 0.001). Dignity symptom distress showed moderate positive correlation with fatigue symptoms (r = 0.541, P < 0.001). Conclusions: Most cancer patients’ dignity were impaired slightly or moderately in North China. Dignity of cancer patients showed significant association with quality of life. Anxiety and depression were more consistent with dignity than other factors. Improving the quality of life and dignity of patients is vital.
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