Artificial intelligence-based analysis of tumor-infiltrating lymphocyte spatial distribution for colorectal cancer prognosis

Background:Artificial intelligence(AI)technology represented by deep learning has made remarkable achievements in digital pathology,enhancing the accuracy and reliability of diagnosis and prognosis evaluation.The spatial distribution of CD3^(+)and CD8^(+)T cells within the tumor microenvironment has been demonstrated to have a significant impact on the prognosis of colorectal cancer(CRC).This study aimed to investigate CD3_(CT)(CD3^(+)T cells density in the core of the tumor[CT])prognostic ability in patients with CRC by using AI technology.Methods:The study involved the enrollment of 492 patients from two distinct medical centers,with 358 patients assigned to the training cohort and an additional 134 patients allocated to the validation cohort.To facilitate tissue segmentation and T-cells quantification in whole-slide images(WSIs),a fully automated workflow based on deep learning was devised.Upon the completion of tissue segmentation and subsequent cell segmentation,a comprehensive analysis was conducted.Results:The evaluation of various positive T cell densities revealed comparable discriminatory ability between CD3_(CT) and CD3-CD8(the combination of CD3^(+)and CD8^(+)T cells density within the CT and invasive margin)in predicting mortality(C-index in training cohort:0.65 vs.0.64;validation cohort:0.69 vs.0.69).The CD3_(CT) was confirmed as an independent prognostic factor,with high CD3_(CT) density associated with increased overall survival(OS)in the training cohort(hazard ratio[HR]=0.22,95%confidence interval[CI]:0.12–0.38,P<0.001)and validation cohort(HR=0.21,95%CI:0.05–0.92,P=0.037).Conclusions:We quantify the spatial distribution of CD3^(+)and CD8^(+)T cells within tissue regions in WSIs using AI technology.The CD3_(CT) confirmed as a stage-independent predictor for OS in CRC patients.Moreover,CD3_(CT) shows promise in simplifying the CD3-CD8 system and facilitating its practical application in clinical settings.

Deep learning quantified mucus-tumor ratio predicting survival of patients with colorectal cancer using whole-slide images

Background:In colorectal cancer(CRC),mucinous adenocarcinoma differs from other adenocarcinomas in gene-phenotype,morphology,and prognosis.However,mucinous components are present in a large number of adenocarcinomas,and the prognostic value of mucus proportion has not been investigated.Artificial intelligence provides a way to quantify mucus proportion on whole-slide images(WSIs)accurately.We aimed to quantify mucus proportion by deep learning and further investigate its prognostic value in two CRC patient cohorts.Methods:Deep learning was used to segment WSIs stained with hematoxylin and eosin.Mucus-tumor ratio(MTR)was defined as the proportion of mucinous component in the tumor area.A training cohort(N=419)and a validation cohort(N=315)were used to evaluate the prognostic value of MTR.Survival analysis was performed using the Cox proportional hazard model.Result:Patients were stratified tomucus-low andmucus-high groups,with 24.1%as the threshold.In the training cohort,patients with mucus-high had unfavorable outcomes(hazard ratio for high vs.low 1.88,95%confidence interval 1.18–2.99,P=0.008),with 5-year overall survival rates of 54.8%and 73.7%in mucus-high and mucus-lowgroups,respectively.The resultswere confirmed in the validation cohort(2.09,1.21–3.60,0.008;62.8%vs.79.8%).The prognostic value of MTR was maintained in multivariate analysis for both cohorts.Conclusion:The deep learning quantified MTR was an independent prognostic factor in CRC.With the advantages of advanced efficiency and high consistency,our method is suitable for clinical application and promotes precision medicine development.