After local excision of early rectal cancer, revision radical resection is recommended for patients with high-risk pathologic stage T1 (pT1) or pT2 cancer, but the revision procedure has high morbidity rates. We evaluated the efficacy of adjuvant concurrent chemoradiotherapy (CCRT) for reducing recurrence after local excision in these patients. Eighty-three patients with high-risk pT1 or pT2 rectal cancer underwent postoperative adjuvant CCRT after local excision. We defined high-risk features as pT1 having tumor size ≤3 cm, and/or resection margin (RM) ≤3 mm, and/or lymphovascular invasion (LVI), and/or non-full thickness excision such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), or unknown records regarding those features, or pT2 cancer. Radiotherapy was administered with a median dose of 50.4 Gy in 1.8 Gy fraction size over 5–7 weeks. Concurrent 5-fluorouracil and leucovorin were administered for 4 days in the first and fifth weeks of radiotherapy. The median interval between local excision and radiotherapy was 34 (range, 11–104) days. Fifteen patients (18.1 %) had stage pT2 tumors, 22 (26.5 %) had RM of ≥3 mm, and 21 (25.3 %) had tumors of ≥3 cm in size. Thirteen patients (15.7 %) had LVI. Transanal excision was performed in 58 patients (69.9 %) and 25 patients (30.1 %) underwent EMR or ESD. The median follow-up was 61 months. The 5-year overall survival (OS), locoregional relapse-free survival (LRFS), and disease-free survival (DFS) rates for all patients were 94.9, 91.0, and 89.8 %, respectively. Multivariate analysis did not identify any significant factors for OS or LRFS, but the only significant factor affecting DFS was the pT stage (p = 0.027). In patients with high-risk pT1 rectal cancer, adjuvant CCRT after local excision could be an effective alternative treatment instead of revision radical resection. However, patients with pT2 stage showed inferior DFS compared to pT1.

Background/Objectives: The tumor microenvironment (TME) has emerged as a significant prognostic factor. This study aimed to identify prognostic factors by combining clinicopathologic parameters and the TME biomarkers in patients who underwent surgery following neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC). Methods: CD8⁺ T cells, CXCR3, CXCL10, and α-smooth muscle actin (α-SMA) were analyzed via immunohistochemical staining. We also incorporated AI-powered digital pathology to assess the spatial TME. The associations between these biomarkers, clinicopathologic parameters, and survival outcomes were evaluated. Results: CD8⁺ T cell expression, CXCR3 expression in tumor-infiltrating lymphocytes (TILs), and immune phenotypes were correlated. LARC patients with a high expression of CD8⁺ T cells, CXCR3 in TILs, and an inflamed phenotype had a significantly better prognosis than their counterparts did. In the multivariate analysis, the expression of CD8⁺ T cells and the inflamed/immune-excluded phenotype were significant tumor immune microenvironment (TiME) biomarkers for recurrence-free survival (RFS) but not for overall survival (OS). Notably, patients with the immune-desert phenotype had a poor prognosis regardless of pathologic stage, even if postoperative chemotherapy was administered (p < 0.001). Conclusions: CD8⁺ T cells and AI-powered immune phenotypes, alongside clinical factors, can guide personalized treatment in LARC patients receiving nCRT. A therapeutic strategy to modify the TiME after nCRT could help reduce recurrence after surgery.

The role of biomarkers in cancer treatment varies significantly depending on the cancer stage. Thus, in clinical practice, tailoring biomarkers to meet the specific needs and challenges of each cancer stage can increase the precision of treatment. Because they reflect underlying genetic alterations that influence cancer progression, copy number variation (CNV) biomarkers can play crucial prognostic roles. In our previous study, we identified potential survival-related genes for colorectal cancer (CRC) by analyzing CNV and gene expression data using a machine-learning approach. To further investigate the biological function of NRXN1, we assessed the use of RNA sequencing, phosphokinase assays, real-time quantitative PCR, and Western blot analysis. We found that NRXN1 copy number deletion was significantly associated with poor overall survival (OS) and recurrence-free survival (RFS), even in patients who received adjuvant chemotherapy. Compared with its expression in normal tissues, NRXN1 expression was lower in tumors, suggesting its potential role as a tumor suppressor. NRXN1 knockdown enhanced CRC cell viability and invasion, and transcriptome analysis indicated that the increased invasion was caused by GSK3β-mediated epithelial–mesenchymal transition. These findings highlight NRXN1 copy number deletion as a novel biomarker for predicting recurrence and survival in patients with resected colon cancer.

Individuals diagnosed with advanced cancer often experience stress and depression, factors linked to worse survival. Curability belief—defined as the hope and expectation of cure through treatment, based on affective forecasting—may differ from the patient’s actual life expectancy (i.e., likelihood estimation) and has shown variable associations with cancer survival. In this study, multivariate Cox regression analyses were used to examine the effect of curability belief and depression on 1-year survival after adjustment for physical factors. Additionally, regularized partial correlations among physical and psychological factors were assessed using mixed graphical models to elucidate their roles in mediating the relationship between curability belief and 1-year survival. This multi-center cohort study, conducted across 13 tertiary hospitals (including four ranked among the ‘World’s Best Specialized Hospitals 2025’ in oncology), involved 382 adults with stage IV advanced cancer and an oncologist-estimated survival of more than 6 months. Baseline data included demographics, primary tumor site, number of metastatic sites, symptom burdens (EORTC QLQ-C15-PAL), performance status (ECOG-PS), depression levels (PHQ-9), anti-cancer treatment type, patient’s life expectancy estimation, and curability belief. Follow-up data included 1-year survival and end-of-life care (place of death) for deceased patients. Multivariate Cox proportional hazards models were used to assess adjusted hazard ratios (aHRs) for curability belief, depression, and their interaction on 1-year survival, adjusting for significant demographic and clinical factors from univariate Cox regressions. The Kaplan–Meier method was used to plot survival probability by curability belief and depression interaction. Mixed graphical models estimated regularized partial correlations among 1-year survival, curability belief, patient’s life expectancy, depression, primary tumor site, anti-cancer treatment type, performance status, and symptom burden. In terms of healthcare utilization, patients with curability belief were more likely to receive standard or advanced anti-cancer therapy, while those without curability belief tended to suspend or discontinue therapy (P < 0.001). Among patients who did not survive the 1-year follow-up (N = 161), end-of-life care settings differed significantly between those with curability belief (predominantly nursing homes and home settings) and those without (primarily hospice and tertiary/secondary hospitals; P = 0.036). In multivariate Cox regression, curability belief (P = 0.003), depression (PHQ-9 score ≥ 10; P = 0.003), and their interaction (P = 0.040) were significantly associated with 1-year survival, after adjusting for sex, residential area, primary tumor site, performance status, anti-cancer treatment type, and symptom burdens (fatigue and appetite loss). The relationship between curability belief and 1-year survival was significant only in patients without depression [PHQ-9 score < 10; aHR (95% CI) = 2.20 (1.31–3.70); P = 0.003]. In the mixed graphical model, node predictability values for curability belief, depression, and 1-year survival were 0.68, 0.50, and 0.70, respectively, with curability belief showing partial correlations with depression (r = 0.30) and patients’ life expectancy (r = 0.20); depression correlated with fatigue (r = 0.53), anorexia (r = 0.16), life expectancy (r = 0.24), performance status (r = 0.23), and curability belief; and 1-year survival correlated with suspended/stopped anti-cancer treatment (r = 0.45), primary tumor site (r = 0.24), and performance status (r = 0.15). Partial correlations of performance status with depression and discontinued treatment mediated the association between curability belief and 1-year survival. Curability belief among stage IV advanced cancer patients with an oncologist-estimated survival of over 6 months was associated with depression levels and patients’ perceived life expectancy estimations. Performance status, depression, and anti-cancer treatment status mediate the relationship between curability belief and improved 1-year survival in patients without depression. Further research using longitudinal modeling of depression, performance status, and healthcare utilization, with curability belief and primary tumor site as covariates, is warranted. Trial registration: Clinical Trial Number (ClinicalTrials.gov): NCT03222258; Study Registration Dates (First submitted: 2017-06-05; First submitted following the QC criteria: 2017-07-16; First posted: 2017-07-19).

Oh SN, et al. J Korean Med Sci. 2020 Nov;35(47):e401. https://doi.org/10.3346/jkms.2020.35.e401

Background: Insulin resistance (IR) disrupts hepatic glucose and lipid metabolism, contributing to metabolic dysfunction-associated steatotic liver disease (MASLD) and progression to severe liver complications. Galectin-3-binding protein (LGALS3BP) is a secreted glycoprotein implicated in inflammation and metabolic disorders. Elevated LGALS3BP levels are associated with MASLD and type 2 diabetes (T2D), but its role in IR remains unclear.Methods: LGALS3BP-deficient models were used to investigate its role in IR and inflammation. Glucose metabolism and insulin signaling were assessed in high-fat diet (HFD)-fed mice. Hepatic cell lines were employed to evaluate the direct effects of LGALS3BP on insulin signaling and inflammation. Mechanistic insights were obtained through RNA sequencing, structural modeling, immunoprecipitation, and protein/gene expression analyses.Results: LGALS3BP deficiency improved insulin sensitivity in HFD-fed mice by enhancing glucose tolerance, lowering serum glucose and insulin, and increasing hepatic insulin signaling, without altering lipid accumulation. In vitro, LGALS3BP deficiency enhanced insulin signaling and suppressed gluconeogenesis, whereas recombinant LGALS3BP impaired insulin signaling and upregulated gluconeogenesis. RNA sequencing revealed activation of Toll-like receptor 2 (TLR2) and nuclear factor-kappa B (NF-κB) pathways by LGALS3BP. Immunoprecipitation confirmed a direct interaction between LGALS3BP and TLR2, leading to inhibitor kappa kinase (IKK)/NF-κB activation and increased insulin receptor substrate-1 (IRS1) serine phosphorylation, a key inhibitory modification in IR. Furthermore, LGALS3BP deficiency attenuated hepatic fibrosis under chronic HFD, accompanied by downregulated inflammatory signaling pathways.Conclusion: LGALS3BP contributes to IR through inflammatory responses, particularly via TLR2-IKKα/β signaling that regulates IRS1 serine phosphorylation. LGALS3BP deficiency improves insulin sensitivity and reduces inflammation, suggesting that targeting LGALS3BP may represent a potential therapeutic strategy for metabolic disorders such as T2D and MASLD.