KCTD9 expression predicts immunotherapy response and enhances anti-PD-1 efficacy in colon adenocarcinoma.

IF 12.5 2区医学 Q1 SURGERY

International journal of surgery Pub Date : 2025-06-25 DOI:10.1097/JS9.0000000000002846

Lei Wu, Shengnan Sun, Pengyuan Song, Changsheng Cong, Ning Liu, Meili Sun, Weichong Zhao

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引用次数: 0

Abstract

Purpose: Colon adenocarcinoma (COAD) is a commonly diagnosed malignancy in the world. While immunotherapy, specifically PD-1/PD-L1, shows potential as a treatment for COAD, its efficacy is limited to a minority of patients. This study sought to explore new biomarker that could predict the response to anti-PD-1/PD-L1 therapies in COAD.

Methods: In this study, KCTD9 was validated as a novel biomarker for predicting immunotherapy efficacy in colon cancer through transcriptomic expression analysis, cellular pathway activity analysis, immune infiltration analysis, and in vivo mouse xenograft tumor formation assays.

Results: Our findings revealed that KCTD9 was correlated with prognosis across multiple cancer types, and as a protective factor, the expression level of KCTD9 exhibited the most significant impact on colon cancer. Furthermore, positive correlations between KCTD9 expression and both microsatellite instability (MSI) and tumor mutational burden (TMB) were observed across multiple tumor types, with the strongest correlations being identified in colon cancer. Finally, high expression of KCTD9 was positively correlated with CD8+ T cell infiltration and CD8-positive α-β T cell activation pathway activity, and significantly enhanced the anti-tumor efficacy of PD-1 inhibitor.

Conclusions: Our data validated the strong association between KCTD9 expression and colon cancer prognosis, as well as its capacity to enhance immunotherapy efficacy, indicating that KCTD9 may represent a promising biomarker for colon cancer.

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KCTD9表达预测免疫治疗反应并增强结肠腺癌抗pd -1疗效。

目的：结肠腺癌（COAD）是世界上常见的恶性肿瘤。虽然免疫疗法，特别是PD-1/PD-L1，显示出治疗COAD的潜力，但其疗效仅限于少数患者。本研究旨在探索新的生物标志物，以预测COAD患者对抗pd -1/PD-L1治疗的反应。方法：在本研究中，通过转录组表达分析、细胞通路活性分析、免疫浸润分析和小鼠体内异种移植肿瘤形成分析，验证了KCTD9作为预测结肠癌免疫治疗疗效的新型生物标志物。结果：我们的研究结果显示，KCTD9与多种癌症类型的预后相关，作为一种保护因子，KCTD9的表达水平对结肠癌的影响最为显著。此外，KCTD9的表达与多种肿瘤类型的微卫星不稳定性（MSI）和肿瘤突变负担（TMB）呈正相关，其中结肠癌的相关性最强。最后，KCTD9的高表达与CD8+ T细胞浸润和CD8阳性α-β T细胞活化途径活性呈正相关，并显著增强PD-1抑制剂的抗肿瘤效果。结论：我们的数据验证了KCTD9表达与结肠癌预后之间的强相关性，以及其增强免疫治疗疗效的能力，表明KCTD9可能是一种有前景的结肠癌生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International journal of surgery SURGERY-

CiteScore

17.70

自引率

3.30%

发文量

审稿时长

6-12 weeks

期刊介绍： The International Journal of Surgery (IJS) has a broad scope, encompassing all surgical specialties. Its primary objective is to facilitate the exchange of crucial ideas and lines of thought between and across these specialties.By doing so, the journal aims to counter the growing trend of increasing sub-specialization, which can result in "tunnel-vision" and the isolation of significant surgical advancements within specific specialties.