Exploring ALK fusion in colorectal cancer: a case series and comprehensive analysis.

Anaplastic lymphoma kinase (ALK) fusion-positive colorectal cancer (CRC) is a rare and chemotherapy-refractory subtype that lacks established and effective treatment strategies. Additionally, the efficacy and safety of ALK inhibitors (ALKi) in CRC remain undetermined. Herein, we examined a series of ALK-positive CRC patients who underwent various lines of ALKi treatment. Notably, we detected an ALK 1196M resistance mutation in a CRC patient who received multiple lines of chemotherapy and ALKi treatment. Importantly, we found that Brigatinib and Lorlatinib demonstrated some efficacy in managing this patient, although the observed effectiveness was not as pronounced as in non-small cell lung cancer cases. Furthermore, based on our preliminary analyses, we surmise that ALK-positive CRC patients are likely to exhibit inner resistance to Cetuximab. Taken together, our findings have important implications for the treatment of ALK-positive CRC patients.

Circular RNA circNCOA3 promotes tumor progression and anti-PD-1 resistance in colorectal cancer.

Aim: Circular RNAs (circRNAs) have been found to be involved in tumor progression, but their role in colorectal cancer (CRC) immune escape remains to be elucidated. Methods: circRNAs differentially expressed in responsive and resistant CRC tissues to programmed cell death 1 (PD-1) antibody therapy were identified by microarray analysis. The clinical and pathological significance of circNCOA3 was validated in a separate cohort of CRC samples. The function of circNCOA3 was explored experimentally. RNA immunoprecipitation and luciferase activity assays were conducted to identify downstream targets of circNCOA3. Results: The circNCOA3 was markedly overexpressed in CRC samples resistant to PD-1 blockade. circNCOA3 expression was significantly correlated with adverse tumor phenotypes and poor outcomes in CRC patients. Knockdown of circNCOA3 expression markedly suppressed the proliferative and invasive capability of CRC cells. Moreover, knockdown of circNCOA3 increased the proportion of CD8+ T cells while decreasing the proportion of myeloid-derived suppressor cells (MDSCs). Knockdown of circNCOA3 inhibited tumor growth and increased the sensitivity to PD-1 antibody treatment in mouse tumor models. Further studies revealed that circNCOA3 acted as a competing endogenous RNA (ceRNA) for miR-203a-3p.1 to influence the level of CXCL1. Conclusion: Our findings indicate that circNCOA3 might be useful as a potential biomarker to predict the efficacy and prognosis of CRC patients treated with anti-PD-1 therapy.

Circular RNA circTNIK promotes tumor progression and metastasis in gastric cancer by regulating ZEB2.

BACKGROUND AND AIM: Tumor progression and distant metastasis are the main causes of deaths in gastric cancer. Growing evidence revealed that circular RNAs (circRNAs) play critical role in the pathology of malignant disease, the role of circRNAs in gastric cancer progression and metastasis is still unknown. METHODS: Differentially expressed circRNAs was identified by circRNA microarray and validated by quantitative reverse transcription polymerase reaction. The biological function of circTNIK was evaluated by in vitro and in vivo experiments after ectopic expression or siRNA mediated knockdown of circTNIK. The interaction between circTNIK and miR-138-5p was determined by luciferase activity assay, RNA immunoprecipitation, and fluorescence in situ hybridization assays. RESULTS: circTNIK rather than linear TINK mRNA was significantly upregulated in gastric cancer tissues, cell lines compared with normal controls. Higher circTNIK expression was correlated with aggressive tumor phenotypes and poor overall survival in gastric cancer patients. Ectopic circTNIK expression promoted cell proliferation, invasion, tumorigenesis, and metastasis in gastric cancer cells whereas knockdown of circTNIK inhibited cell proliferation, invasion, tumorigenesis, and metastasis in gastric cancer cells. Importantly, circTNIK functions as a molecular sponge for miR-138-5p to regulate the expression of ZEB2. CONCLUSIONS: Overall, our study demonstrates how circTNIK regulates gastric cancer progression and metastasis by sponging miR-138-5p to modulate the expression of ZEB2. CircTNIK might be used as a prognostic biomarker in gastric cancer patients.

Case report: PD-1 inhibitor-based treatment strategies in gastric cancer complicated by bone marrow metastasis and disseminated intravascular coagulation: A report of two cases.

Introduction: Gastric cancer (GC) complicated by bone marrow metastasis (BMM) and disseminated intravascular coagulation (DIC) represents poor prognosis and most of these patients would die in a few months. Active treatment strategies such as chemotherapy are effective in restoring coagulation function and prolonging patients' survival time. Immunotherapy including programmed death protein 1 (PD-1) or programmed death protein ligand 1 (PD-L1) inhibitors has emerged as a first-line treatment of gastric cancer. However, the efficacy of PD-1 inhibitor-based treatment strategies in these patients remains unknown. Case description: Herein, we presented two cases of advanced gastric cancer (AGC) complicated by BMM and DIC, in which two patients received chemotherapy and PD-1 inhibitor as the first-line treatment. Both of them achieved a partial response after treatment, and the coagulation function was restored. The patient who discontinued the PD-1 inhibitor after 6 months experienced DIC relapse, whereas the other patient who maintained the PD-1 inhibitor treatment cycle remained responsive after 10 months. Conclusions: We speculate that PD-1 inhibitor-based treatment strategies are effective and safe in prolonging survival against gastric cancer with BMM and DIC, and the coagulation function is well controlled by the treatment with a combination of immunotherapy and chemotherapy.

Comprehensive Analysis of Clinicopathological and Molecular Features to Predict Anti-PD-1-Based Therapy Efficacy in Patients with Advanced Gastric Signet Ring Cell Carcinoma.

BACKGROUND: Signet ring cell carcinoma (SRCC) is a specific type of gastric cancer. The clinicopathological and molecular characteristics that can be used to predict the response to anti-PD-1 therapy for these patients are still not clear. METHODS: Patients with advanced SRCC who received first-line anti-PD-1-based treatment were enrolled in this study. The clinicopathological characteristics of these patients were obtained from their medical records. The molecular features of these patients were analyzed by means of a next-generation-sequencing-based panel. The predictive significance of clinicopathological and molecular features for efficacy was analyzed. RESULTS: A total of 71 patients with measurable lesions were included in this study, among which 46 patients had enough tissues for next-generation sequencing. The overall objective response rate (ORR) was 46.4%. ORR was significantly higher in mismatch repair (MMR)-deficient (dMMR) patients than in MMR-proficient (pMMR) patients, in patients with lymph node metastasis only than those with other metastasis sites, and in patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 than with a PS of 1 or 2. The progression-free survival was significantly longer in patients with dMMR, lymph node metastasis only, PD-L1 combined positive score (CPS) ≥ 5, and CDH1 wild type. CONCLUSIONS: Several clinicopathological and molecular features are associated with anti-PD-1 treatment efficacy in SRCC, which might be used to identify patients who can benefit most from these therapies.

Circular RNAs: Emerging regulators of glucose metabolism in cancer.

Aberrant glucose metabolism is one of the most striking characteristics of metabolic reprogramming in cancer. Thus, clarifying the regulatory mechanism of glucose metabolism is crucial to understanding tumor progression and developing novel therapeutic strategies for cancer patients. Recent developments in circular RNAs have explained the regulatory mechanism of glucose metabolism from a new dimension. In this review, we briefly summarize the recent advances in circRNA research on cancer glucose metabolism and emphasize the different regulatory mechanisms, including acting as miRNA sponges, interacting with proteins and being translated into proteins. Additionally, we discuss the future research directions of circular RNAs in the field of glucose metabolism.

Fracture gap of the lateral malleolus via posterolateral approach: Improved visualization of the posterior malleolus fracture.

The treatment of posterior malleolar fractures is a popular issue. Anatomic reduction of posterior malleolar fractures is critical for re-establishing the stability of the ankle mortise and ligamentous union after trauma. Inappropriate treatment ultimately leads to poorer functional outcomes and lower quality of life. Open reduction and internal fixation through a posterolateral approach are preferred over indirect reduction and anterior-posterior screw fixation. Although the posterolateral approach, which is more common and direct, provides good exposure to the fracture site, it has some limitations. In this report, we describe the posterolateral approach through the lateral ankle fracture gap for the treatment of posterior ankle fractures. Moreover, we discuss the indications, benefits, and limitations of this approach.

LncRNA TMPO-AS1 promotes esophageal squamous cell carcinoma progression by forming biomolecular condensates with FUS and p300 to regulate TMPO transcription.

Esophageal squamous cell carcinoma (ESCC) is one of the most life- and health-threatening malignant diseases worldwide, especially in China. Long noncoding RNAs (lncRNAs) have emerged as important regulators of tumorigenesis and tumor progression. However, the roles and mechanisms of lncRNAs in ESCC require further exploration. Here, in combination with a small interfering RNA (siRNA) library targeting specific lncRNAs, we performed MTS and Transwell assays to screen functional lncRNAs that were overexpressed in ESCC. TMPO-AS1 expression was significantly upregulated in ESCC tumor samples, with higher TMPO-AS1 expression positively correlated with shorter overall survival times. In vitro and in vivo functional experiments revealed that TMPO-AS1 promotes the proliferation and metastasis of ESCC cells. Mechanistically, TMPO-AS1 bound to fused in sarcoma (FUS) and recruited p300 to the TMPO promoter, forming biomolecular condensates in situ to activate TMPO transcription in cis by increasing the acetylation of histone H3 lysine 27 (H3K27ac). Targeting TMPO-AS1 led to impaired ESCC tumor growth in a patient-derived xenograft (PDX) model. We found that TMPO-AS1 is required for cell proliferation and metastasis in ESCC by promoting the expression of TMPO, and both TMPO-AS1 and TMPO might be potential biomarkers and therapeutic targets in ESCC.

LINC01088 promotes the growth and invasion of glioma cells through regulating small nuclear ribonucleoprotein polypeptide A transcription.

Altered long non-coding RNAs (LncRNAs) exert pivotal parts in pathogenic processes in glioma. Here, we uncovered a differentially expressed long intergenic non-coding RNA 1088 (LINC01088) in glioma and elucidated the molecular mechanism by which LINC01088 affected the malignant phenotypes of glioma cells. Functionally, LINC01088 silencing degraded cell proliferation, invasion in glioma, while LINC01088 overexpression elicited opposite results. Mechanistically, we verified LINC01088 physically interacted with small nuclear ribonucleoprotein polypeptide A (SNRPA) and regulated the expression of SNRPA at the transcription level. Phenotypic analysis ascertained that LINC01088 substantively aggravated glioma cell progression in an SNRPA-dependent manner, and SNRPA played a pivotal part in the tumor-promoting properties of LINC01088. Our findings revealed a novel mechanism by which LINC01088 exerted pro-oncogenic functions through binding with SNRPA and transcriptionally regulating SNRPA mRNA in glioma.

Evaluation of right ventricular systolic and diastolic dysfunctions in patients with type 2 diabetes mellitus with poor glycemic control by layer specific global longitudinal strain and strain rate.

BACKGROUND: In order to evaluate right ventricular (RV) systolic and diastolic dysfunctions in patients with type 2 diabetes mellitus (T2DM) with poor glycemic control by layer specific global longitudinal strain (GLS) and strain rate (GLSr). METHODS: 68 T2DM patients and 66 normal controls were enrolled for the present study. RV layer specific GLS (GLSEpi, GLSMid and GLSEndo represent the epimyocardial, middle layer and endomyocardial strains, respectively) and GLSr (GLSr-S, GLSr-E and GLSr-A represent the systole, early-diastole and late-diastole strain rate) were calculated by averaging each of the three regional peak systolic strains and strain rates along the entire RV free-wall (RVFW), entire RV free-wall and septal wall (RVFSW) on RV-focused view. RESULTS: The absolute values of RV layer specific GLS (GLSEpi, GLSMid and GLSEndo) in RVFW in T2DM patients were significantly lower than normal controls (P < 0.01), while GLSr-A was significantly larger than normal controls (P < 0.001). The absolute values of RV layer specific GLS (GLSEpi and GLSMid) in RVFSW in T2DM patients were significantly lower than normal controls (P < 0.05), while GLSr-A was significantly larger than normal controls (P < 0.001). HbA1c were poor negatived correlated with GLSEpi in RVFW and RVFSW in T2DM patients (P < 0.05). ROC analysis showed that RV layer specific GLS and GLSr-A had a high diagnostic efficacy in T2DM patients, and GLSr-A in RVFSW have the best diagnostic value in RV diastolic function in T2DM patients (AUC: 0.773). CONCLUSION: From the research, we found that layer specific GLS and GLSr could detect the RV myocardial dysfunctions and confirmed that the impaired RV systolic and diastole functions in T2DM patients with poor glycemic control. GLSr-A in RVFSW had the best diagnostic value in evaluating RV diastolic function in T2DM patients.

Concentration-dependent dual effects of exogenous sucrose on nitrogen metabolism in Andrographis paniculata.

The effects of exogenous sucrose (Suc) concentrations (0, 0.5, 1, 5, 10 mmol L-1) on carbon (C) and nitrogen (N) metabolisms were investigated in a medicinal plant Andrographis paniculata (Chuanxinlian). Suc application with the concentration of 0.5-5 mmol L-1 significantly promoted plant growth. In contrast, 10 mmol L-1 Suc retarded plant growth and increased contents of anthocyanin and MDA and activity of SOD in comparison to 0.5-5 mmol L-1 Suc. Suc application increased contents of leaf soluble sugar, reducing sugar and trerhalose, as well as isocitrate dehydrogenase (ICDH) activity, increasing supply of C-skeleton for N assimilation. However, total leaf N was peaked at 1 mmol L-1 Suc, which was consistent with root activity, suggesting that exogenous Suc enhanced root N uptake. At 10 mmol L-1 Suc, total leaf N and activities of glutamine synthase (GS), glutamate synthase (GOGAT), NADH-dependent glutamate dehydrogenase (NADH-GDH) and glutamic-pyruvic transaminase (GPT) were strongly reduced but NH4+ concentration was significantly increased. The results revealed that exogenous Suc is an effective stimulant for A. paniculata plant growth. Low Suc concentration (e.g. 1 mmol L-1) increased supply of C-skeleton and promoted N uptake and assimilation in A. paniculata plant, whereas high Suc concentration (e.g. 10 mmol L-1) uncoupled C and N metabolisms, reduced N metabolism and induced plant senescence.

Synthesis and Characterization of Novel Radiopaque Polycarbonate.

Polymeric materials implanted in the human body are usually invisible under X-ray, and the mixing of heavy metal salts into polymeric materials by physical compounding often poses compatibility problems. A new iodine-containing cyclic carbonate monomer, 4-iodo-N-(2-oxo-1,3-dioxan-5-yl)benzamide (IBTMC), is synthesized, which has a degradable carbonate group as its basic structural unit and iodine atoms attached to the side chain in the form of covalent bonds. The ring-opening polymerization of IBTMC is achieved at room temperature under the catalysis of the solid superbase 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD). The structure and X-ray developing ability of the synthesized polycarbonate are characterized by 1 H-NMR, X-ray photoelectron spectroscopy (XPS), energy dispersive X-ray spectroscopy (EDS), Gel Permeation Chromatography (GPC), and micro-computed tomography (Micro-CT). The iodine atoms remain bound to the polymer as covalent bonds after a series of reactions and exhibit a high level of X-ray opacity. In vitro degradation experiments of the polymer prove that the polymer is degradable.

The circular RNA circDLG1 promotes gastric cancer progression and anti-PD-1 resistance through the regulation of CXCL12 by sponging miR-141-3p.

BACKGROUND: Dysregulation of circular RNAs (circRNAs) plays an important role in the development of gastric cancer; thus, revealing the biological and molecular mechanisms of abnormally expressed circRNAs is critical for identifying novel therapeutic targets in gastric cancer. METHODS: A circRNA microarray was performed to identify differentially expressed circRNAs between primary and distant metastatic tissues and between gastric cancer tissues sensitive or resistant to anti-programmed cell death 1 (PD-1) therapy. The expression of circRNA discs large homolog 1 (DLG1) was determined in a larger cohort of primary and distant metastatic gastric cancer tissues. The role of circDLG1 in gastric cancer progression was evaluated both in vivo and in vitro, and the effect of circDLG1 on the antitumor activity of anti-PD-1 was evaluated in vivo. The interaction between circDLG1 and miR-141-3p was assessed by RNA immunoprecipitation and luciferase assays. RESULTS: circDLG1 was significantly upregulated in distant metastatic lesions and gastric cancer tissues resistant to anti-PD-1 therapy and was associated with an aggressive tumor phenotype and adverse prognosis in gastric cancer patients treated with anti-PD-1 therapy. Ectopic circDLG1 expression promoted the proliferation, migration, invasion, and immune evasion of gastric cancer cells. Mechanistically, circDLG1 interacted with miR-141-3p and acted as a miRNA sponge to increase the expression of CXCL12, which promoted gastric cancer progression and resistance to anti-PD-1-based therapy. CONCLUSIONS: Overall, our findings demonstrate how circDLG1 promotes gastric cancer cell proliferation, migration, invasion and immune evasion and provide a new perspective on the role of circRNAs during gastric cancer progression.

The Prognostic Value of Locoregional Interventions for BRAF V600E Metastatic Colorectal Cancer: A Retrospective Cohort Analysis.

The prognostic heterogeneity in patients with BRAF V600E metastatic colorectal cancer (mCRC) remains poorly defined. Real-world data of 93 BRAF V600E mCRC patients from Sun Yat-sen University Cancer Center were evaluated using the prognostic factors affecting overall survival (OS). Treatment of metastases served as an independent prognosticator, where curative locoregional interventions (LRIs) were associated with superior clinical outcomes (adjusted hazard ratio (HR): 0.46, 95% confidence interval (CI): 0.22-0.98; p = 0.044). The LRIs group showed an improved median OS of 49.4 months versus 18.3 months for the palliative treatments (PTs) group. The median OS of patients with colorectal liver metastasis (CRLM) was significantly prolonged after undergoing LRIs (42.4 vs. 23.7 months; HR: 0.11, 95% CI: 0.01-1.22; p = 0.030), and patients in the LRIs plus liver-limited or lung-limited metastasis (LLM) group benefited more than those in the LRIs plus non-LLM group when compared to the PTs group (LLM from LRIs vs. PTs, HR: 0.16, 95% CI: 0.04-0.68; p = 0.006. Non-LLM from LRIs vs. PTs, HR: 0.47, 95% CI: 0.21-1.05; p = 0.074). In conclusion, we confirmed the positive prognostic value of LRIs in BRAF V600E mCRC, particularly in patients with CRLM or LLM.

Organic nitrogen sources promote andrographolide biosynthesis by reducing nitrogen metabolism and increasing carbon accumulation in Andrographis paniculata.

Nitrogen (N) form affects secondary metabolites of medicinal plants, but the physiological and molecular mechanisms remain largely unknown. To fully understand the response of andrographolide biosynthesis to different N forms in Andrographis paniculata, the plants were fed with nutritional solution containing sole N source of nitrate (NO3-), ammonium (NH4+), urea or glycine (Gly), and the growth, carbon (C) and N metabolisms and andrographolide biosynthesis were analyzed. We found that plants grown in urea and Gly performed greater photosynthetic rate and photosynthetic N use efficiency (PNUE) than those grown in NO3- and NH4+. Organic N sources reduced the activities of enzymes involving in C and N metabolisms such as glutamine synthase (GS), glutamate synthase (GOGAT) and NADH-dependent glutamate dehydrogenase (NADH-GDH), invertase (INV), isocitrate dehydrogenase (ICDH) and glycolate oxidase (GO), resulting in reduced depletion of carbohydrates and increased starch accumulation. However, they enhanced andrographolide content by up-regulating the key genes in its biosynthetic pathway including HMGR, DXS, GGPS and ApCPS. Besides, NH4+ decreased leaf SPAD value, contents of soluble protein and amino acids and GO activity, but increased photosynthetic rate and contents of soluble sugar and starch in comparison to NO3-. Andrographolide biosynthesis was also up-regulated. The results revealed that increasing accumulation of carbohydrates, especially starch, was beneficial to the biosynthesis of andrographolide; organic N sources decreased carbohydrate depletion by reducing N metabolism, and promoted plant growth and andrographolide biosynthesis synergistically.

Baseline lesion number as an efficacy predictive and independent prognostic factor and its joint utility with TMB for PD-1 inhibitor treatment in advanced gastric cancer.

BACKGROUND: We previously reported tumor mutation burden (TMB) as a potential prognostic factor for patients with advanced gastric cancer (AGC) receiving immunotherapy. We aimed to comprehensively understand the impact of tumor burden and TMB on efficacy and prognosis in immunotherapy-treated AGC patients. METHODS: A total of 58 patients with refractory AGC receiving PD-1 inhibitor monotherapy from a phase Ib/II clinical trial (ClinicalTrials.gov identifier: NCT02915432) were retrospectively included. Univariate and multivariate logistical regression analyses and the Cox proportional hazards model were performed for prognostic value of baseline factors. Factors reflecting baseline tumor burden, including baseline lesion number (BLN), the maximum tumor size (MTS) and the sum of target lesion size (SLS) were analyzed. The objective response rate (ORR) and disease control rate (DCR) were compared by Chi-square test. RESULTS: In univariate analysis, high BLN was associated with poor median progression-free survival (mPFS) [1.7 months versus 3.4 months; hazard ratio (HR), 2.696, p < 0.05] and median overall survival (mOS) (3.2 months versus 7.6 months; HR, 1.997, p < 0.05), while high TMB was a positive prognostic factor. In multivariable analysis, both BLN and TMB were independent prognostic factors for mOS (BLN: HR, 2.782, p < 0.05; TMB: HR, 0.288, p < 0.05), while MTS or SLS had no association with survival. Better ORR and DCR were observed in the low BLN group (15.4% versus 5.3%, p > 0.05; 86.96% versus 54.29%, p < 0.05). When combining BLN and TMB, the best efficacy and survival were observed in the BLNlowTMBhigh group (ORR: 37.5%, DCR: 62.5%, mPFS and mOS: not reached). The worst efficacy and survival were shown in the BNLhighTMBlow group [ORR: 0% (0/15); DCR: 13.3%; mPFS: 1.7 months; mOS: 2.7 months (all p < 0.05)]. CONCLUSIONS: BLN, rather than factors regarding baseline tumor size, is perhaps a potential predictor for benefit from immunotherapy and its combination with TMB could further risk-stratify patients with AGC receiving immunotherapy.

PD-L1 expression in liver metastasis: its clinical significance and discordance with primary tumor in colorectal cancer.

BACKGROUND: The outcomes of immune checkpoint inhibitors in cancer patients with liver metastases are poor, which may be related to a different tumor microenvironment in liver metastases from primary tumors. This study was aimed to analyze PD-L1 expression and the immune microenvironment status in liver metastases and compare the differences of PD-L1 expression between primary tumors and liver metastases of colorectal cancer. METHODS: 74 cases of pathologically confirmed colorectal cancer with liver metastasis underwent resection from our hospital were included. Tissue microarrays were used for the interpretation of PD-L1 expression, cluster of differentiation 4 (CD4) and CD8 density by immunohistochemistry. We evaluated the disparity between primary tumor and liver metastasis in PD-L1 expression, CD4 and CD8 density and analyzed the factors associated with obvious PD-L1 disparity. RESULTS: The expression of PD-L1 was positively related to the density of CD4 and CD8 in liver metastases. The expression of PD-L1 in liver metastases was higher than in primary tumors in certain subgroups, including patients with concurrent liver metastases (n = 63, p = 0.05), patients receiving concurrent resection of primary and metastatic tumors (n = 56, p = 0.04). The two subgroups generally reflected those without inconsistent external influences, such as treatment and temporal factors, between primary tumors and liver metastases. In these subgroups, the intrinsic differences of microenvironment between primary tumors and liver metastases could be identified. Furthermore, tumor differentiation [moderate vs. poor: OR = 0.23, 95% CI: 0.03-0.99, p = 0.05)] were demonstrated to be associated with obvious discordance of PD-L1 expression between primary tumors and liver metastases. CONCLUSIONS: The expression of PD-L1 in liver metastases was higher than in primary tumors in subgroups, reflecting intrinsic microenvironment differences between primary and metastatic tumors. Obvious discordance of PD-L1 expression between primary tumor and liver metastasis was significantly related to the tumor differentiation.

The predicting role of circulating tumor DNA landscape in gastric cancer patients treated with immune checkpoint inhibitors.

A more common and noninvasive predicting biomarker for programmed cell death 1 (PD-1) antibody remains to be explored. We assessed 46 patients with advanced gastric cancer who received PD-1 antibody immunotherapy and 425-genes next-generation sequencing (NGS) testing. Patients who had a > 25% decline in maximal somatic variant allelic frequency (maxVAF) had a longer progression free survival (PFS) and higher response rate than those who did not (7.3 months vs 3.6 months, p = 0.0011; 53.3% vs 13.3%, p = 0.06). The median PFS of patients with undetectable and detectable post-treatment circulating tumor DNA (ctDNA) was 7.4 months vs. 4.9 months (p = 0.025). Mutation status of TGFBR2, RHOA, and PREX2 in baseline ctDNA influenced the PFS of immunotherapy (p < 0.05). Patients with alterations in CEBPA, FGFR4, MET or KMT2B (p = 0.09) gene had greater likelihood of immune-related adverse events (irAEs). ctDNA can serve as a potential biomarker of the response to immunotherapy in advanced gastric cancers, and its potential role in predicting irAEs worth further exploration.