Zanif Umaimah, Parks Jaclyn, Tai Isabella, Yip Stephen, Babinszky Sindy, Milne Katy, Watson Peter, Murphy Rachel A, Bhatti Parveen
Cancer Control Research, BC Cancer Research Institute, Vancouver, Canada.
Genome Sciences Centre, BC Cancer Research Institute, Vancouver, Canada.
Biomark Insights. 2025 May 21;20:11772719251339955. doi: 10.1177/11772719251339955. eCollection 2025.
Demographic, health history, and lifestyle factors have been associated with prognosis of colorectal cancer (CRC), but mechanisms underlying these associations remain poorly understood. A compelling mechanism involves changes in expression of tumor markers that influence treatment outcomes, such as secreted protein acidic and rich in cysteine (SPARC), lower levels of which have previously been associated with poorer CRC prognosis.
We explored the association of factors that have been previously associated with CRC prognosis with expression of SPARC in tumor tissues.
We conducted a prospective evaluation of 50 participants of a longitudinal cohort study that went on to develop CRC.
Tumor and normal tissue cores were taken from formalin-fixed paraffin-embedded (FFPE) blocks of incident CRC cases and were used to create tissue microarrays (TMAs). Slides created from the TMAs were stained with SPARC antibodies and analyzed to calculate H-scores for both epithelial and non-epithelial components of tumor and normal tissues. H-scores were ln-transformed and analyzed in association with demographic, lifestyle, and health history factors assessed before cancer diagnosis using linear regression models.
In CRC tumor epithelium, smoking was associated with a 0.53-fold lower level of SPARC expression ( = .054). Higher income was associated with a 1.33-fold greater level of SPARC expression in tumor non-epithelial tissue ( = .041). Higher cancer stage was associated with a 0.74-fold lower level of non-epithelial tumor SPARC expression ( = .040). In the epithelial component of normal colorectal tissues, higher fruit consumption was associated with a 2.74-fold greater SPARC H-score ( = .002).
The associations we observed for smoking, income, and cancer stage with SPARC in tumor tissue are consistent with previously established associations of these factors with CRC prognosis. Larger studies with prognostic data are needed, but our results suggest that differences in SPARC expression may contribute to previously observed impacts of various factors on CRC prognosis.
人口统计学、健康史和生活方式因素与结直肠癌(CRC)的预后相关,但这些关联背后的机制仍知之甚少。一个引人注目的机制涉及影响治疗结果的肿瘤标志物表达变化,如富含半胱氨酸的酸性分泌蛋白(SPARC),其水平较低先前已与较差的CRC预后相关。
我们探讨了先前与CRC预后相关的因素与肿瘤组织中SPARC表达的关联。
我们对50名纵向队列研究参与者进行了前瞻性评估,这些参与者后来发展为CRC。
从新发病例的福尔马林固定石蜡包埋(FFPE)块中获取肿瘤和正常组织芯,并用于制作组织微阵列(TMA)。由TMA制作的玻片用SPARC抗体染色,并进行分析以计算肿瘤和正常组织上皮和非上皮成分的H评分。对H评分进行对数转换,并使用线性回归模型与癌症诊断前评估的人口统计学、生活方式和健康史因素进行关联分析。
在CRC肿瘤上皮中,吸烟与SPARC表达水平降低0.53倍相关(P = 0.054)。较高收入与肿瘤非上皮组织中SPARC表达水平升高1.33倍相关(P = 0.041)。较高的癌症分期与非上皮肿瘤SPARC表达水平降低0.74倍相关(P = 0.040)。在正常结直肠组织的上皮成分中,较高的水果摄入量与SPARC H评分升高2.74倍相关(P = 0.002)。
我们观察到吸烟、收入和癌症分期与肿瘤组织中SPARC的关联与这些因素先前与CRC预后建立的关联一致。需要进行更大规模的具有预后数据的研究,但我们的结果表明,SPARC表达的差异可能导致先前观察到的各种因素对CRC预后的影响。