Background:Emerging evidence indicates that the lncRNA FAM83A-AS1 interacts closely with HIF-1α to modulate malignant biological behaviors and glycolytic metabolism in CRC. The mechanism underlying the effects of artemisinin on colorectal cancer (CRC) was investigated using a network pharmacology approach. Methods:The action network of artemisinin was analyzed using network pharmacology. Stable FAM83A-AS1 and HIF-1α knockout cell models were established using a lentiviral system. The effects of artemisinin on cellular functions, including proliferation, metastasis, cell cycle progression, and glycolysis in CRC cells, were assessed through in vitro assays. The expression of HIF-1α was assessed by immunohistochemistry in tumor tissues from 219 patients with CRC, and its clinical associations were analyzed. Results:Artemisinin was predicted to target 96 proteins associated with CRC, including HIF-1α. Artemisinin inhibited proliferation, migration, and glycolysis, and induced cell cycle arrest in CRC cells. Artemisinin reduced the expression levels of Cyclin D1, CDK4, HIF-1α, PKM2, and N-cadherin. Artemisinin promoted proteasome-mediated degradation of HIF-1α protein. HIF-1α upregulated the expression of FAM83A-AS1, whereas knockdown of FAM83A-AS1 reduced HIF-1α expression levels. The expression level of HIF-1α in tumor tissues was significantly higher than that in adjacent non-tumor tissues. HIF-1α expression was associated with tumor node metastasis (TNM) stage, tumor (T)stage, node (N)stage, carcinoembryonic antigen (CEA) levels, recurrence, metastasis, and prognosis in patients with CRC. Conclusions:Artemisinin promoted proteasome-mediated degradation of HIF-1α protein and inhibited CRC progression, potentially through the FAM83A-AS1/HIF-1α regulatory axis.
Background:The combination of atezolizumab plus bevacizumab is a standard first-line therapy for advanced hepatocellular carcinoma (HCC). However, the liver possesses a uniquely immunosuppressive microenvironment that often leads to discordant therapeutic responses between intrahepatic lesions and extrahepatic metastases. Conventional assessments relying on binary Response Evaluation Criteria in Solid Tumors (RECIST) criteria have failed to capture the organ-specific longitudinal dynamics. This exploratory study evaluated the organ-specific antitumor dynamics of atezolizumab plus bevacizumab in patients with advanced HCC presenting with extrahepatic metastases. Methods:We retrospectively analyzed 42 consecutive patients with extrahepatic metastases who received atezolizumab plus bevacizumab for HCC at Kanazawa University Hospital between October 2020 and November 2024. Best overall response (BOR), objective response rate (ORR), and disease control rate (DCR) were evaluated per RECIST version 1.1. Organ-specific response rates (OSRR), depth of response (DpR), duration of response (DoR), and time to progression (TTP) were also evaluated. Results:The BORs (complete response/partial response/stable disease/progressive disease) were 0/13/15/14 patients, respectively, yielding an ORR of 31% and a DCR of 67%. OSRRs were 30% in the liver, 11% in the lung, 50% in lymph nodes, and 57% in peritoneal dissemination, and 0% in bone and adrenal glands. The median DpR was 1% in the liver, 7% in the lung, -28% in lymph nodes, -32% in peritoneal dissemination, 9% in bone (n=2), and 8% in adrenal glands (n=3), with no significant differences among organs (P=0.31). Median DOR and TTP were 16.5 and 9.7 months for the liver, not reached and 5.5 months for the lung, not reached and 21.3 months for lymph nodes, and 15.9 and 19.8 months for peritoneal dissemination, respectively, without significant differences. Although no statistically significant differences were observed across organs in median DpR (P=0.31), DoR (P=0.37), or TTP (P=0.09), these exploratory comparisons were severely underpowered due to the restricted sample size and subgroup fragmentation. Conclusions:Atezolizumab plus bevacizumab combination therapy showed no significant differences in organ-specific efficacy and demonstrated consistent antitumor effects regardless of intrahepatic disease or metastatic site. elicited objective tumor responses across diverse intrahepatic and extrahepatic sites. While the small sample size precludes a definitive conclusion of uniform efficacy, the descriptive trends showing preserved intrahepatic efficacy support the clinical rationale of this regimen in advanced HCC.
Background:Membrane Spanning 4-Domains A3 (MS4A3) has been confirmed to possess significant tumor-suppressive potential in various malignancies. However, its expression characteristics and clinical prognostic value in colon cancer (CC) still lack systematic and in-depth investigation. This study aimed to systematically investigate the expression pattern, prognostic value, immune microenvironment association, and biological function of MS4A3 in CC through integrated bioinformatics analyses and experimental validation. Methods:This study utilized The Cancer Genome Atlas-Colon Adenocarcinoma (TCGA-COAD) cohort to screen for genes significantly associated with CC and combined multiple independent Gene Expression Omnibus (GEO) datasets to validate the expression patterns and prognostic significance of MS4A3. Key biological pathways were identified through gene set enrichment analysis (GSEA), and tumor immune infiltration characteristics were evaluated using the CIBERSORT algorithm. Additionally, the expression of MS4A3 and its impacts on cellular functions were validated at the cellular level through quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, Cell Counting Kit-8 (CCK-8), EdU, Transwell, and TUNEL assays. Results:Analysis of public datasets revealed that MS4A3 is significantly downregulated in CC tissues, and its low expression is an independent risk factor for shortened overall survival (OS). GSEA indicated that MS4A3 downregulation is closely associated with the aberrant activation of the pentose phosphate pathway. Immune infiltration analysis showed that low MS4A3 expression is closely linked to the enrichment of M2 macrophages and neutrophils, as well as the upregulation of multiple immune checkpoint genes. In vitro experiments further confirmed that MS4A3 was lowly expressed in CC cell lines. Its overexpression significantly inhibited CC cell viability, proliferation, migration, and invasion, while simultaneously promoting cell apoptosis. Conclusions:MS4A3 expression is significantly decreased in CC tissues and is significantly correlated with poor prognosis, suggesting that this gene may serve as a potential prognostic biomarker.
Background:Ribonucleic acid export 1 (RAE1) autoantibody may have good potential for early detection of gastric cancer (GC). However, the carcinogenicity of RAE1 in GC remains unknown. We aimed to explore the role and the potential mechanism for RAE1 in the carcinogenesis of GC. Methods:Immunohistochemical assay was applied to analyze the expression of RAE1 in GC and precancerous lesion (PL) tissues and its relationship with clinical characteristics. The effects of RAE1 on proliferation, migration, apoptosis, and cell cycle were explored by constructing RAE1 knockdown and overexpression in GC cells. The effects of RAE1 knockdown on tumor growth were observed in a murine xenograft model. The signaling pathways involved in GC development that may be affected by RAE1 were investigated by transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Results:Immunohistochemical expression of RAE1 was significantly higher in early GC patients than in PL and normal tissues, and the RAE1 expression was correlated with clinical stage (P<0.001). In vitro, knockdown of RAE1 inhibited the proliferation and migration of GC cells with promoted apoptosis and arrested cell cycle in the S phase, while overexpression of RAE1 showed the opposite trend. In vivo, knockdown of RAE1 inhibited the growth of subcutaneous graft tumors in mice. Transcriptome sequencing and subsequent analysis of RAE1 knockdown cells revealed that the Hippo signaling pathway was activated by RAE1 knockdown. Conclusions:RAE1 promotes GC cells proliferation and migration and is associated with the inhibition of the Hippo signaling pathway, and may be a potential biomarker for early diagnosis and treatment of GC.
Background:Accurate preoperative assessment of lymphovascular invasion (LVI) in patients with rectal cancer (RC) is important for guiding postoperative management. This study aimed to develop and validate a deep learning model based on magnetic resonance imaging (MRI)-derived microvascular network simulation parameters for the preoperative assessment of LVI in RC patients. Methods:A total of 453 patients with pathologically confirmed rectal adenocarcinoma from two medical centers were retrospectively enrolled. All patients underwent multi-b-value diffusion-weighted imaging (DWI) before surgery. First, a steady-state Navier-Stokes hemodynamic model of the tumor microvascular network was constructed based on the multi-b-value DWI images. Subsequently, voxel-wise least squares fitting was performed to match the DWI signals with the dictionary, enabling the inversion and generation of spatial parametric maps for mean flow velocity (V-m), velocity standard deviation (V-s), and angiogenic branching index (ANB). These parametric maps were then input into a Vision Transformer (ViT) network to extract deep features from each modality. A cross-attention fusion module was designed to capture spatial interactions among the parametric maps and construct a multiparametric fusion model. The model's performance was comprehensively evaluated using the area under the curve (AUC), calibration curves, and decision curve analysis (DCA). Results:The multiparametric fusion model achieved favorable performance, with AUCs of 0.901 [95% confidence interval (CI): 0.808-0.993] and 0.863 (95% CI: 0.800-0.926) in the internal and external validation cohorts, respectively. DCA demonstrated that within the threshold range of 0.2-0.8, the fusion model provided substantially greater clinical net benefit than the individual parameter models. Gradient-weighted Class Activation Mapping (Grad-CAM) visualization revealed that the model's attention was primarily focused on the invasive front of the tumor and regions with high peritumoral vascular density, providing supportive visual evidence and suggesting potential biological relevance. Conclusions:The deep learning model based on MRI-simulated microvascular network parameters provides a promising and noninvasive approach for the preoperative assessment of LVI status in RC patients. The model demonstrated encouraging performance in both internal and external validation cohorts. However, further prospective and multicenter validation is required before clinical application.
Background:KDM1B, a flavin-dependent histone demethylase, is an epigenetic regulator implicated in tumorigenesis; however, its role in esophageal squamous cell carcinoma (ESCC) remains unclear. We aimed to explore the biological role of KDM1B in ESCC and, on this basis, to develop a prognostic prediction model incorporating KDM1B. Methods:Public transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO; GSE26886 and GSE161533) were analyzed to assess KDM1B expression, prognostic relevance, pathway enrichment, and immune infiltration in ESCC. KDM1B genomic alterations were further examined in 52 ESCC specimens from our center. Functional assays were performed in ESCC cell lines to evaluate the effects of KDM1B on proliferation, migration, and apoptosis. Overall survival (OS) was the primary prognostic outcome. Univariable and multivariable Cox regression analyses were performed to construct a prognostic prediction model for estimating 1-, 3-, and 5-year OS. Results:KDM1B was significantly upregulated in ESCC compared with normal esophageal epithelium and was associated with a higher response rate to systemic therapy. In our cohort, intronic variants and copy-number alterations of KDM1B were detected in a subset of tumors. Functional enrichment analyses suggested that KDM1B may be involved in cell-cycle regulation and apoptosis, and its expression was associated with immune infiltration. Survival analyses showed that elevated KDM1B expression was associated with longer OS. A prognostic prediction model incorporating KDM1B expression, pathologic node stage (N stage), pathologic metastasis stage (M stage), overall pathologic stage, gender, and histologic grade was developed to estimate 1-, 3-, and 5-year OS in patients with ESCC. In vitro experiments showed that KDM1B promoted ESCC cell proliferation and migration while inhibiting apoptosis, suggesting a context-dependent role in ESCC biology, potentially influenced by treatment and the immune microenvironment. Conclusions:KDM1B is upregulated in ESCC and may influence tumor behavior through regulation of the cell cycle, apoptosis, and the tumor immune microenvironment. KDM1B was also incorporated into a prognostic prediction model for OS estimation in ESCC, supporting its potential value in prognostic stratification.
Background:Sex determining region Y-box 18 (SOX18) has been found to be overexpressed in several types of tumors. However, the molecular mechanism underlying the biological function of SOX18 in colorectal cancer (CRC) remains unclear. This study aims to investigate the effect of SOX18 gene knockdown on proliferation, invasion, angiogenesis and its relationship to SAPK/JNK and PI3K/AKT/mTOR signaling pathways in CRC cells. Methods:The Cancer Genome Atlas (TCGA)‑CRC dataset was analyzed to assess the clinical correlation of SOX18 expression. SOX18 was knocked down in OUMS‑23 and HCT116 CRC cells. Cell proliferation, migration, invasion, apoptosis, and angiogenesis were evaluated by functional assays. Western blot and quantitative real‑time polymerase chain reaction (qPCR) were used to detect pathway activity. The JNK agonist anisomycin was applied for rescue experiments, while the AKT inhibitor MK‑2206 was used for pathway validation. Results:High SOX18 expression correlated with poor prognosis in CRC patients. SOX18 knockdown significantly inhibited proliferation, migration, invasion, and angiogenesis, while promoting apoptosis in CRC cells and human umbilical vein endothelial cells (HUVECs). Mechanistically, SOX18 silencing suppressed the phosphorylation of JNK, AKT, and mTOR, and downregulated HIF‑1α/VEGF expression. Anisomycin‑mediated JNK activation selectively restored p‑JNK and fully reversed the tumor‑suppressive and anti‑angiogenic effects of SOX18 knockdown. In contrast, MK‑2206 further inhibited the PI3K/AKT/mTOR pathway without altering JNK activity. Conclusions:SOX18 knockdown suppresses CRC metastasis and angiogenesis by regulating SAPK/JNK and PI3K/AKT/mTOR signaling pathways.
Background:Autophagy has been implicated in the regulation of programmed death-ligand 1 (PD-L1) expression in gastric cancer (GC) through a p62/SQSTM1-nuclear factor-κB (NF-κB) pathway. However, the adaptor complexes linking p62 to NF-κB activation and the functional impact of this axis on T-cell apoptosis remain incompletely understood. This study aimed to investigate the role of p62/SQSTM1-TRAF6/RIP1 complexes in NF-κB-mediated PD-L1 expression and their effects on T-cell proliferation, apoptosis, and cytokine secretion in MKN-45 gastric cancer cells. Methods:Human GC MKN45 cells were treated with the autophagy inhibitor chloroquine (CQ) and the NF-κB inhibitor, respectively. Following transfection with p62/SQSTM1 knockdown plasmids, cells were treated with CQ. PD-L1 and pathway-related molecules were assessed by real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence. Protein-protein interactions were examined by co-immunoprecipitation. A co-culture system of MKN45 cells and activated human T cells was established to evaluate T-cell proliferation with Cell Counting Kit-8 (CCK-8), apoptosis with cleaved caspase-3 and cytokine production [interferon-γ (IFN-γ), interleukin-10 (IL-10) and tumour necrosis factor-α (TNF-α) by enzyme-linked immunosorbent assay (ELISA)]. Results:CQ treatment in MKN45 cells resulted in autophagy blockade accompanied by p62/SQSTM1 accumulation, NF-κB activation and increased PD-L1 expression at both messenger ribonucleic acid (mRNA) and protein levels. Modulation of p62 expression confirmed that p62 was required for CQ-induced NF-κB activation and PD-L1 up-regulation. Co-immunoprecipitation experiments demonstrated that p62 formed complexes with TRAF6 and RIP1, and that these interactions were enhanced by p62 overexpression or CQ treatment but attenuated by p62 knockdown. Functionally, co-culture with CQ-treated or p62-overexpressing MKN45 cells suppressed T-cell proliferation, increased T-cell apoptosis and decreased IFN-γ, IL-10 and TNF-α secretion. These effects were partially reversed by p62 knockdown, NF-κB inhibition. Conclusions:This study improves our molecular understanding of the p62/SQSTM1-NF-κB-PD-L1 signalling pathway by implicating TRAF6 and RIP1 as adaptor proteins in MKN45 GC cells. It also provides evidence that activation of this pathway promotes T-cell apoptosis and cytokine suppression. These results suggest that p62/NF-κB/PD-L1 signalling could be targeted to enhance anti-tumour immunity in GC.
Background:Prognostic stratification at the initiation of chemotherapy is clinically important in patients with metastatic or recurrent unresectable pancreatic cancer. The lactate dehydrogenase-to-albumin ratio (LAR) is an objective blood-based index that combines tumor-associated activities with systemic conditions of the host; however, evidence of its usefulness as a prognostic index in patients receiving first-line gemcitabine plus nab-paclitaxel (GnP) remains limited. In this study, we evaluated the prognostic value of baseline LAR in these patients. Methods:This single-center retrospective cohort study included consecutive patients with metastatic or recurrent unresectable pancreatic cancer who underwent first-line GnP between 2015 and 2024. Baseline LAR was calculated from laboratory data obtained within 7 days before treatment initiation, and neutrophil-to-lymphocyte ratio (NLR) was evaluated as a comparative inflammatory marker. The primary analysis evaluated the association between baseline LAR and overall survival (OS) using prespecified multivariable Cox proportional hazards models. The functional form of LAR was examined using restricted cubic splines (RCS). Kaplan-Meier curves were then presented to visualize risk stratification by combining Eastern Cooperative Oncology Group performance status (ECOG PS) with LAR. The incremental prognostic performance beyond the base clinical model was evaluated using model fit and discrimination metrics, with bootstrap internal validation. Results:The final analytic cohort comprised 205 patients (median age, 67 years; 63.9% men). The median baseline LAR was 4.94. In the prespecified multivariable model, ECOG PS and LAR were independently associated with OS [PS 2 vs. 0: hazard ratio (HR), 2.38; 95% confidence interval (CI), 1.28-4.42; LAR per 1-standard deviation (SD) increase: HR, 1.29; 95% CI, 1.09-1.52]. RCS analysis demonstrated a significant overall association without evidence of nonlinearity (overall P=0.03; nonlinear P=0.71). Kaplan-Meier curves for four risk groups defined by PS (0-1 vs. 2) and LAR (below vs. at/above the median) showed significant separation (log-rank P<0.001). The base + PS + LAR model showed the best fit and discrimination among the evaluated models [Akaike's information criterion (AIC), 1,320.3; Harrell's concordance index (C-index), 0.662]. Conclusions:Baseline LAR was independently associated with OS after adjustment for ECOG PS in patients receiving first-line GnP. Therefore, PS combined with LAR may enable simple prognostic stratification at treatment initiation, pending confirmation in future external validation cohorts.
Background:In recent years, reports using urinary Titin (U-Titin) levels to evaluate patients with muscular dystrophy, myocardial infarction, myasthenia gravis, gastrointestinal malignancy (GIM), chronic liver disease, and sarcopenia have been sporadically observed; however, reports using serum Titin (S-Titin) levels are scarce. We report here on the measurement of S-Titin, which has now become feasible. Methods:This study included 104 patients who underwent surgery for the diagnosis of GIM in our department between May 2024 and November 2025. Preoperative S-Titin and U-Titin levels were measured to investigate their correlation. Furthermore, using InBody, we measured skeletal muscle mass index (SMI), percent body fat (PBF), fat mass index (FMI), extracellular water (ECW)/total body water (TBW) and whole-body phase angle (Ph A) to investigate the relationship with S-Titin and U-Titin. Results:There were 28 female and 76 male patients, with a median age of 68 (range, 54-89) years. Location of malignant diseases was as follows: 42 cases of hepatobiliary-pancreatic cancer, 36 cases of colorectal cancer, and 26 cases of upper gastrointestinal cancer. S-Titin and U-Titin levels showed a strong positive correlation (r=0.78, y=0.19x+1.40, P<0.001). PBF, FMI, and Ph A showed a weak negative correlation with both levels, while ECW/TBW showed a weak positive correlation, however, no correlation was observed with SMI. Conclusions:This study suggests that S-Titin levels, like U-Titin levels, may serve as a potential biomarker for skeletal muscle and nutritional disorders in GIM patients.
Background:Perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) is the standard treatment for resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma, with fluorouracil administered at 2,600 mg/m2 as a 24-hour continuous infusion. However, toxicity can limit treatment delivery in routine practice. Dose-modified FLOT regimens are frequently used to improve tolerability, though data supporting clinical outcomes are limited. This study aimed to evaluate the safety, treatment delivery, and clinical outcomes of a predefined modified perioperative FLOT regimen in routine clinical practice. Methods:We conducted a retrospective cohort study of patients with resectable gastric or GEJ adenocarcinoma treated with predefined, modified perioperative FLOT at three institutions between 2019 and 2025. The regimen consisted of fluorouracil 2,400 mg/m2 over 46-48 hours, oxaliplatin 85 mg/m2, and docetaxel 40-50 mg/m2. Safety, treatment delivery, and clinical outcomes were assessed, with survival estimated using Kaplan-Meier methods. Results:Twenty-nine patients were included (median age 66 years; 62% male; 59% gastric and 34% GEJ tumors). Curative-intent resection was achieved in 86% of patients, with an R0 resection rate of 88% and a pathological complete response (pCR) rate of 16%. At a median follow-up of 30.3 months, median overall survival (OS) was 53.6 months (3-year OS 75.3%), and median recurrence-free survival (RFS) was 46.1 months (3-year RFS 52.4%). Grade 3 or higher neutropenia occurred in 34% of patients, and infections in 10%; no treatment-related deaths were observed. Conclusions:In this multi-institutional, real-world cohort, modified perioperative FLOT was associated with acceptable treatment delivery, manageable toxicity, and favorable clinical outcomes in selected patients with resectable gastric and GEJ adenocarcinoma. These findings support the feasibility of dose-modified FLOT in routine clinical practice, particularly for patients at risk for treatment-related toxicity.
Background:Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer lacking personalized pathological parameters. Microscopic tumor focus (MTF), a microscopic intrahepatic metastatic pattern, remains poorly characterized, with unclear prognostic and therapeutic relevance in cHCC-CCA. In this study, the detailed significance of MTF in cHCC-CCA was investigated. Methods:A multicenter study included 310 cHCC-CCA patients who underwent curative-intent hepatectomy. MTF was further graded by its number/distribution (MTF 0: absence of MTF; MTF 1: 1-5 proximal MTFs; MTF 2: >5 proximal MTFs/≥1 distal MTFs) and subclassified by its histology (HCC-type MTF; CCA-type MTF; HCC + CCA-type MTF). Results:MTF was detected in 48.1% (149/310) of patients (MTF 1: 43.2%, MTF 2: 4.8%; HCC-type MTF: 17.7%; CCA-type MTF: 20.6%; HCC + CCA type MTF: 9.7%). MTF positivity correlated with poorer recurrence-free survival (RFS) (median time: 0.23 and 0.89 years), early RFS, and overall survival (OS) (median time: 1.53 and 2.95 years, all P<0.001), with MTF 2 and HCC + CCA-type MTF predicting the worst prognosis. For MTF-positive patients, surgical margin >0.1 cm improved RFS, early RFS, and OS, while surgical margin had no effect on MTF-negative patients. Age, tumor diameter, microvascular invasion and perineural invasion independently predicted MTF (area under the curve =0.704); MTF histology was an independent prognostic factor for RFS, early RFS, and OS (all Harrell's concordance index >0.7). Conclusions:This study standardized the definition of MTF and confirmed its prognostic value in cHCC-CCA. MTF stratification based on its number/distribution and histology enables more precise prognostic assessment. The presence of MTF could guide individualized selection of surgical margin.
Background:Serum cholinesterase (CHE) and C-reactive protein (CRP) are established prognostic markers in gastric cancer, but their levels after two cycles of therapy are rarely incorporated into predictive models. This study aimed to develop a nomogram integrating post-treatment CHE and CRP levels after two cycles of first-line therapy to predict progression-free survival (PFS) in patients with stage III-IV gastric adenocarcinoma. Methods:This retrospective study included 104 treatment-naïve patients with stage III-IV gastric adenocarcinoma who received first-line therapy. Serum CHE and CRP were measured after two cycles. Optimal prognostic cut-off values were determined by maximally selected rank statistics and validated via bootstrap resampling. Independent prognostic factors were identified by Cox regression to construct a nomogram. Model performance was evaluated using the concordance index (C-index), calibration plots, time-dependent receiver operating characteristic (ROC) analysis, and decision curve analysis (DCA). Overfitting was quantified by repeated K-fold cross-validation. Public transcriptomic data were analyzed via gene set variation analysis (GSVA) to explore associated pathways. Results:Optimal cut-off values were 4,865 U/L for CHE and 2.58 mg/L for CRP, confirmed by bootstrap validation. Multivariate analysis identified low post-treatment CHE (≤4,865 U/L) as an independent protective factor for PFS [hazard ratio (HR) =0.36; 95% confidence interval (CI): 0.20-0.63; P<0.001]. Elevated CRP (>2.58 mg/L) (HR =1.67; 95% CI: 0.99-2.84; P=0.06) and peritoneal metastasis (HR =1.66; 95% CI: 0.93-2.95; P=0.09) were associated with increased risk. The nomogram achieved a C-index of 0.709 (95% CI: 0.652-0.766), improving to 0.751 after cross-validation adjustment. Time-dependent ROC yielded areas under the curve (AUCs) of 0.789, 0.836, and 0.760 for 6-, 12-, and 18-month PFS, respectively. Risk stratification based on nomogram scores revealed significantly poorer PFS in the high-risk group (P<0.001). Bioinformatics analysis suggested upregulation of the complement and coagulation cascades pathway in advanced gastric cancer, correlating with poorer prognosis and M2-type macrophage infiltration. Conclusions:A nomogram incorporating post-treatment CHE and CRP levels after two therapy cycles enables individualized PFS prediction and risk stratification in advanced gastric adenocarcinoma. The associated complement pathway may underlie an immunosuppressive tumor microenvironment.
Background:Gastric adenocarcinoma is infrequently associated with synchronous or metachronous second malignancies. Even more rare is the presence of two cancers within the same anatomical site. It is unclear if an association exists between the development of diffuse large B-cell lymphoma (DLBCL) and gastric signet ring cell adenocarcinoma (SRCC). We present a case of a woman who presented with both malignancies. Case Description:We present a 67-year-old woman with a complex past medical history including a Roux-en-Y gastric bypass who presented with abdominal pain and profuse diarrhea. Initial endoscopy images did not show signs of obvious malignancy, but subsequent random biopsies from the gastric pouch demonstrated SRCC. Staging imaging and procedures did not show metastases or nodal involvement, so she was subsequently diagnosed with Tumor, Node, Metastasis (TNM) stage 1A gastric SRCC. She had total gastrectomy with esophagojejunostomy. Post-surgical biopsies showed DLBCL of the gastric pouch. The prior SRCC was not noted despite extensive sampling of the resected specimens. She was treated with six cycles of chemoimmunotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for the DLBCL. Subsequent scans showed a new renal mass, but she passed away before further investigations could be done. Conclusions:A potential association exists that led to the development of SRCC and DLBCL in the same anatomical site in our patient. We highlight how this challenging case was managed, and the various unusual aspects.
