Department of Urology, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China.
Department of Urinary Surgery, The Third Affiliated Hospital of Naval Medical University, Shanghai, China.
Cancer Med. 2023 Feb;12(4):3962-3971. doi: 10.1002/cam4.5229. Epub 2022 Sep 12.
Searching for reliable indicators for evaluating prognosis diagnosed with clear cell renal cell carcinoma (ccRCC) is crucial for improving clinical therapies. However, current researches have looked mainly at the prognostic value of a single intratumoral indicator, neglecting tumor-infiltrating immune cells (TIICs) in the microenvironment. This study examined whether the integration of Ring finger protein 43 (RNF43) expression and CD163 tumor-associated macrophage (TAM) infiltration in combination with clinical indexes forecast ccRCC patient outcome with relatively high accuracy. Firstly, the expression of RNF43 and CD163 were detected with immunohistochemistry. Totally, 346 ccRCC patients were random separated evenly into training and validation datasets to make further analyses. We found that RNF43 expression was negatively correlated with infiltration level of CD163 TAM in ccRCC, which was closely associated with the TNM stage and outcome of these patients. The multiple regression analysis demonstrated that RNF43, CD163, and TNM stage could function as independent risk factors in overall survival (OS) and progression-free survival (PFS) prediction of ccRCC. Furthermore, a better postoperative prognosis index for ccRCC patients was obtained by combining RNF43 and CD163 TAMs, which assessed with time-dependent C-index analyses and a nomogram. Consequently, combining RNF43 and CD163 TAMs along with TNM stage acquired robust accuracy in forecasting outcome of patients with ccRCC. In conclusion, combining intratumoral RNF43 expression, CD163 TAM infiltration, and TNM stage could significantly enhance the veracity in forecasting postoperative outcomes.
寻找可靠的指标来评估透明细胞肾细胞癌(ccRCC)的预后对于改善临床治疗至关重要。然而,目前的研究主要关注单个肿瘤内指标的预后价值,而忽略了肿瘤微环境中的浸润免疫细胞(TIICs)。本研究探讨了 RNF43 表达和 CD163 肿瘤相关巨噬细胞(TAM)浸润的综合指标与临床指标相结合,能否以较高的准确性预测 ccRCC 患者的预后。首先,通过免疫组织化学检测 RNF43 和 CD163 的表达。总共,346 例 ccRCC 患者被平均随机分为训练集和验证集,以进行进一步分析。我们发现 RNF43 的表达与 ccRCC 中 CD163 TAM 的浸润水平呈负相关,与这些患者的 TNM 分期和预后密切相关。多因素回归分析表明,RNF43、CD163 和 TNM 分期可以作为预测 ccRCC 患者总生存期(OS)和无进展生存期(PFS)的独立危险因素。此外,通过时间依赖性 C 指数分析和列线图评估,结合 RNF43 和 CD163 TAMs 获得了更好的 ccRCC 患者术后预后指数。因此,结合 RNF43 和 CD163 TAMs 以及 TNM 分期可以显著提高预测 ccRCC 患者预后的准确性。总之,联合肿瘤内 RNF43 表达、CD163 TAM 浸润和 TNM 分期可以显著提高预测术后结局的准确性。