SARIFA (Stroma AReactive Invasion Front Areas) has recently emerged as a promising histopathological biomarker for colon and gastric cancer. To elucidate the underlying tumor biology, we assessed SARIFA-status in tissue specimens from The-Cancer-Genome-Atlas (TCGA) cohorts COAD (colonic adenocarcinoma) and READ (rectal adenocarcinoma). For the final analysis, 207 CRC patients could be included, consisting of 69 SARIFA-positive and 138 SARIFA-negative cases. In this external validation cohort, H&E-based SARIFA-positivity was strongly correlated with unfavorable overall, disease-specific, and progression-free survival, partly outperforming conventional prognostic factors. SARIFA-positivity was not associated with known high-risk genetic profiles, such as BRAF V600E mutations or microsatellite-stable status. Transcriptionally, SARIFA-positive CRCs exhibited an overlap with CRC consensus molecular subtypes CMS1 and CMS4, along with distinct differential gene expression patterns, linked to lipid metabolism and increased stromal cell infiltration scores (SIIS). Gene-expression-based drug sensitivity prediction revealed a differential treatment response in SARIFA-positive CRCs. In conclusion, SARIFA represents the H&E-based counterpart of an aggressive tumor biology, demonstrating a partial overlap with CMS1/4 and also adding a further biological layer related to lipid metabolism. Our findings underscore SARIFA-status as an ideal biomarker for refined patient stratification and novel drug developments, particularly given its cost-effective assessment based on routinely available H&E slides.
SARIFA（基质无反应性侵袭前沿区域）作为结肠癌和胃癌的一种新型组织病理学生物标志物近期备受关注。为阐明其潜在肿瘤生物学机制，我们基于癌症基因组图谱（TCGA）队列中的结肠腺癌（COAD）和直肠腺癌（READ）组织样本评估了SARIFA状态。最终分析共纳入207例结直肠癌患者，其中69例为SARIFA阳性，138例为阴性。在此外部验证队列中，基于H&E染色的SARIFA阳性与较差的总生存期、疾病特异性生存期和无进展生存期显著相关，其预测效能部分优于传统预后因素。SARIFA阳性与已知高危遗传特征（如BRAF V600E突变或微卫星稳定状态）无相关性。转录组分析显示，SARIFA阳性结直肠癌与共识分子分型CMS1/CMS4存在重叠，同时呈现与脂质代谢相关的独特差异基因表达模式及更高的基质细胞浸润评分（SIIS）。基于基因表达的药物敏感性预测揭示了SARIFA阳性结直肠癌的差异化治疗反应。结论表明，SARIFA是基于H&E染色反映侵袭性肿瘤生物学的标志物，不仅与CMS1/4存在部分重叠，更增加了脂质代谢相关的生物学层面。本研究结果证实SARIFA status是精细化患者分层和新药研发的理想生物标志物——尤其因其能通过常规H&E切片实现经济高效的评估。
肿瘤(癌症)患者之家