Value of the combination of intraepithelial tumor-infiltrating lymphocyte density and the heterogeneity of density as a prognostic marker in stage III colorectal cancers.

IF 2.5 4区 生物学 Q3 CELL BIOLOGY
Hye-Yeong Jin, Lingyan Jin, Seung Yeon Yoo, Nam-Yun Cho, Jeong Mo Bae, Jung Ho Kim, Hye Seung Lee, Gyeong Hoon Kang
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引用次数: 0

Abstract

Tumor-infiltrating lymphocyte (TIL) density is both a prognostic and a predictive factor in colorectal cancer (CRC). Whether the heterogeneity of TIL density across the tumor plays an important role in the clinical outcome of CRC is not well known. Adjuvant chemotherapy-treated patients with stage III CRC were analyzed for survival according to TIL density and density heterogeneity, which were determined on CD8-immunostained slides using a machine learning method and by calculating the Simpson evenness index, respectively. High heterogeneity of the intraepithelial TIL density was found to be an independent prognostic factor, with a hazard ratio of 1.970 (1.207-3.215) in the multivariate analysis of recurrence-free survival. High heterogeneity was closely associated with a high T category, venous invasion, perineural invasion, and KRAS mutation. The combination of both intraepithelial TIL density and density heterogeneity was significantly associated with the prognosis of patients: low TIL density/high TIL heterogeneity showed hazard ratios of 3.284 (1.639-6.578) and 4.176 (1.713-10.178) in the discovery and validation cohorts, respectively. Our findings suggest that the heterogeneity status of intraepithelial TIL density might help delineate patients with better vs. worse survival when combined with intraepithelial TIL density.

上皮内肿瘤浸润性淋巴细胞密度及其异质性作为III期结直肠癌预后指标的价值
肿瘤浸润性淋巴细胞(TIL)密度是结直肠癌(CRC)的预后和预测因素。肿瘤间TIL密度的异质性是否在结直肠癌的临床结局中起重要作用尚不清楚。根据TIL密度和密度异质性分析III期CRC辅助化疗患者的生存情况,分别使用机器学习方法和计算Simpson均匀指数在cd8免疫染色的载片上确定TIL密度和密度异质性。在无复发生存的多因素分析中,发现上皮内TIL密度的高度异质性是一个独立的预后因素,其风险比为1.970(1.207-3.215)。高异质性与高T分型、静脉侵犯、神经周围侵犯和KRAS突变密切相关。上皮内TIL密度和密度异质性的结合与患者的预后显著相关:在发现和验证队列中,低TIL密度/高TIL异质性的风险比分别为3.284(1.639-6.578)和4.176(1.713-10.178)。我们的研究结果表明,当结合上皮内TIL密度时,上皮内TIL密度的异质性状态可能有助于描述患者的生存率更好或更差。
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来源期刊
Histology and histopathology
Histology and histopathology 生物-病理学
CiteScore
3.90
自引率
0.00%
发文量
232
审稿时长
2 months
期刊介绍: HISTOLOGY AND HISTOPATHOLOGY is a peer-reviewed international journal, the purpose of which is to publish original and review articles in all fields of the microscopical morphology, cell biology and tissue engineering; high quality is the overall consideration. Its format is the standard international size of 21 x 27.7 cm. One volume is published every year (more than 1,300 pages, approximately 90 original works and 40 reviews). Each volume consists of 12 numbers published monthly online. The printed version of the journal includes 4 books every year; each of them compiles 3 numbers previously published online.
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