Tertiary lymphoid structures combined with clinicopathological features to predict the prognosis of colorectal cancer in stage Ⅲ
Objective This study aims to investigate the prognostic significance of the relative area of tertiary lymphoid structures(TLS)in patients with stage Ⅲ colorectal cancer(CRC).By combining the relative area of TLS with important clinicopathological indicators such as tumor-stroma percentage(TSP),perineural invasion(PNI),and tumor deposit(TD),a Nomogram was developed to assess the prognosis of patients with stage Ⅲ CRC.Methods This retrospective study enrolled clinical data from 199 patients with primary CRC who underwent radical surgical resection at the Gastrointestinal Surgery Department of Shanghai General Hospital from January 2014 to December 2018.TLS number,area,average density,rel-ative area,hotspot density,and tumor-infiltrating edge length were manually delineated and assessed using the Qupath visualization software on hematoxylin and eosin(HE)-stained slides.The TSP was evaluated u-sing a rapid multi-dynamic threshold machine algorithm(TSP-CAD).Pathological data,including perineu-ral invasion and TDs,were collected from the pathology reports.The cut-off values for the above indicators were determined using the X-tile analysis tool,and patients were grouped based on these cutoff values.De-mographic data and clinical characteristics between the high and low TLS relative area groups were com-pared using x2 test,Fisher's exact test,or Kruskal-Wallis H test.Kaplan-Meier survival curves were gen-erated,and log-rank tests were employed to evaluate differences in survival distributions.Univariate Cox regression analysis was performed to explore the relationship between TLS,clinical pathological features,and overall survival(OS),and multivariate Cox regression analysis was used to identify independent prog-nostic factors.A nomogram for predicting 1-,2-,and 5-year survival in stage Ⅲ CRC patients was con-structed using TLS and other significant clinical pathological features.A risk score(RiskScore)based on the nomogram total score was established,and patients were stratified into different risk groups.Internal validation was performed using K-fold cross-validation,and the performance of the nomogram was evaluated using the concordance index(C-index),receiver operating characteristic(ROC)curve,and calibration curve.Results Among 199 patients with stage Ⅲ CRC,the 5-year survival time in the high-level TLS relative area group[(56.919±2.091)months]was longer than that in the low-level group[(43.350±3.512)months],with a statistically significant difference(x2=4.332,P＜0.05).The 5-year survival time in the negative perineural invasion group[(55.590±2.051)months]was longer than in the positive group[(46.018±3.808)months],with a statistically significant difference(x2=6.337,P＜0.05).The 5-year survival time in the negative tumor deposit group[(54.774±2.028)months]was longer than that in the positive group[(46.018±3.808)months],with a statistically significant difference(x2=6.860,P＜0.05).Similarly,the 5-year survival time in the low-level TSP-CAD group[(55.157±2.005)months]was significantly longer than in the high-level group[(43.350±3.512)months],with a statisti-cally significant difference(x2=6.771,P＜0.05).No significant differences were observed in demograph-ic and clinical pathological variables such as gender,age,tumor size,tumor location,tumor type,T stage,N stage,perineural invasion,vascular invasion,tumor deposits,TSP-CAD,and MSI between the high and low TLS relative area groups(x2=0.018,0.467,0.131,1.402,1.218,-1.822,-1.053,0.308,0.272,1.228,0.105,0.829,P＞0.05).Univariate Cox regression analysis identified TLS rela-tive area[HR=0.42(95％CI:0.18-0.97)],TSP-CAD[HR=2.61(95％CI:1.23-5.51)],PNI[HR=2.61(95％CI:1.21-5.65)],and TD[HR=2.62(95％CI:1.24-5.55)]as prognostic factors for CRC(P＜0.05).Multivariate Cox regression confirmed TLS relative area[HR=0.29(95％CI:0.12-0.75)],TSP-CAD[HR=2.98(95％CI:1.34-6.63)],PNI[HR=2.83(95％CI:1.23-6.53)],and TD[HR=3.18(95％CI:1.40,7.22)]as independent prognostic factors(P＜0.05).The relative area of TLS combined with TSP,PNI,TD,T stage,N stage,age,and sex constructed the nomogram.In the modelled group,the 5-year survival of the low-risk group was better than that of the high-risk group[HR=16.85(95％CI:6.09-46.61),P＜0.01].The nomogram showed excellent performance with a C-index of 0.85(95％CI:0.79-0.92)and areas under the ROC curve(AUC)of 0.87,0.91,and 0.96 for 1-,2-,and 5-year survival,respectively.Internal validation using 10-fold cross-validation yielded an AUC of 0.9,and the calibration curve demonstrated good consistency.The nomogram developed by combining TLS rela-tive area,TSP-CAD,PNI,and TD exhibited robust discriminatory ability and accuracy[AUC=0.96,95％CI=0.89-1.00,P＜0.01].Conclusion TLS relative area is an independent prognostic factor for overall survival(OS)in stage Ⅲ colorectal cancer(CRC).The Nomogram developed by combining TLS relative area with clinical pathological indicators such as TSP-CAD,PNI,and TD provides a reliable and effective tool for predicting the prognosis of patients with stage Ⅲ CRC.
Tertiary lymphoid structureColorectal cancer in stage ⅢOverall survivalNomogram
NETL
NSTL
万方数据
