MSI (Microsatellite instability)

Immunotherapy with atezolizumab (1200 mg every 3 weeks [Q3W]) combined with targeted therapy with bevacizumab (600 mg Q3W) was initiated in July 2021.A substantial temporal gap of approximately 21 months followed, after which electroacupuncture-based rehabilitation (5-Hz continuous-wave, stimulating Jiaji acupoints, Zusanli, etc) was started in May 2023. Targeted immunotherapy combined with electroacupuncture may influence neural remodeling by modulating a pro-reparative inflammatory microenvironment, which could potentially support functional reconstruction in patients with spinal metastases. However, there is no direct evidence that immunotherapy accelerates neural recovery, and these observations should be interpreted as hypothesis-generating findings requiring rigorous testing in prospective studies.

We also highlight clinically relevant biomarkers, including MSI/MMR status, tumor mutational burden, immune contexture, Immunoscore, circulating tumor DNA, microbiome profiles, and spatial or AI-assisted multi-marker models. This review summarizes emerging strategies to enhance therapeutic efficacy in CRC and maps each modality to the tumor-intrinsic or tumor-extrinsic resistance barriers it is most likely to overcome.

Analyses separating stain-related from morphology-related components suggested that, in this setting, prediction changes were predominantly associated with morphology-related rather than stain-related alterations. Overall, MoPaDi is a practical framework for counterfactual explanations in computational pathology that supports the evaluation of model-specific decision cues and hypothesis generation.

Specifically, we identified GDF15 as key tumor-cell ligands that may interact with precursor CAFs to promote POSTN+ CAF differentiation. Our findings uncover a stromal mechanism of ICB resistance in dMMR/MSI-H CRC mediated by POSTN+ CAFs and highlight novel therapeutic strategies to enhance immunotherapy efficacy.

P1/2, N=125, Completed, Xilio Development, Inc. | Active, not recruiting --> Completed

Advances in molecular profiling and immunotherapy are reshaping the management of cholangiocarcinoma, enabling more personalized treatment strategies. Continued integration of precision oncology into clinical practice and prospective trials will be critical to improving outcomes for cholangiocarcinoma moving forward.

These findings highlight the heterogeneity of immune checkpoint expression patterns and provide preliminary, hypothesis-generating insights into variability in response to PD-1/PD-L1 blockade.

Due to limited germline and epigenetic data, MSI-H tumors could not be classified as Lynch-associated or sporadic. Overall, MSI-H and MSS CRCs in the Chinese population demonstrate distinct molecular landscapes in terms of TMB, HRD, EBV status, and driver gene alterations, underscoring the molecular heterogeneity of MSI-H CRC and the need for future studies integrating germline and epigenetic data to refine subtype classification.

In this review, we integrate evidence from hepatocellular carcinoma, pancreatic ductal adenocarcinoma, cholangiocarcinoma, colorectal cancer, gastric cancer, esophageal cancer, and gallbladder cancer within a unified framework that links KMT2C domain architecture to enhancer-network destabilization, phenotypic state transitions, and clinical manifestations. We further propose a functional evaluation paradigm that reframes discrete KMT2C variants as graded states of epigenetic deficiency, coupled with a closed-loop validation strategy integrating tissue-based profiling, liquid biopsy monitoring, and spatial multi-omics analyses.

This study provides a comprehensive single-cell atlas of CD27+ cytotoxic T cell heterogeneity in CRC, revealing exhaustion dynamics, regulatory networks, and spatial organization patterns. Our findings highlight the differential immunogenic capacity between MSI-H and MSS tumors and identify potential therapeutic targets for reversing T cell exhaustion in colorectal cancer.

LoY is a frequent chromosomal alteration in metastatic CRC and appears enriched in rectal primary tumors in our cohort. Its association with clinical outcome may depend on disease stage, molecular background, and analytical methodology. These findings support further investigation of Y chromosome loss as a context-dependent biomarker in CRC.

Ordinal logistic, linear NB, and quasi-Poisson models achieved the best or near-best power across a range of zero proportions, dispersion levels, and distributions. The ordinal logistic, linear NB, and quasi-Poisson models are useful and robust options for epidemiologic analyses of overdispersed, right-skewed multi-omic data with a nontrivial proportion of zero counts.