University Department of Surgery, Faculty of Medicine-University of Glasgow, Royal Infirmary, Glasgow G31 2ER, UK.
Br J Cancer. 2010 Sep 7;103(6):870-6. doi: 10.1038/sj.bjc.6605855. Epub 2010 Aug 17.
Cancer incidence is increasing in the United Kingdom, as well as on a global basis. Biochemical parameters, such as C-reactive protein and albumin (combined to form the modified Glasgow Prognostic Score, mGPS), alkaline phosphatase (Alk phos), gamma-glutamyl transferase (GGT) and serum calcium have been reported to be associated with cancer and non-cancer mortality. Therefore, to definitively examine the interrelationships between the above biochemical parameters, the mGPS and the presence of cancer, the Glasgow Inflammation Outcome Study was undertaken. The aim of this initial study was to examine the effect of cancer on markers of systemic inflammation induced by the liver (mGPS) and on levels of routine biochemical parameters.
Patients (n=223 303) who had a single incidental sample taken for C-reactive protein, albumin, calcium and serum liver function tests where available, between 2000 and 2008 were studied. Those with a pathological diagnosis of cancer (n=22 715) were identified. The mGPS was constructed and liver function tests classified in accordance with the local reference ranges.
Patients with cancer had higher C-reactive protein and lower albumin levels (and thus a higher mGPS), higher adjusted calcium, Alk phos and GGT levels, but lower aspartate transaminase (AST) and alanine transaminase (ALT) levels (all P<0.001). The strongest associations (Spearman's correlation > or =0.3) in both the non-cancer and cancer groups were found between albumin, C-reactive protein and Alk phos, AST and ALT, AST and GGT and ALT and GGT (all P<0.001). On multivariate analysis, the associations with the presence of cancer remained with age, deprivation, C-reactive protein, albumin, adjusted calcium, Alk phos and GGT (all P<0.01). Patients following a diagnosis of cancer had lower albumin levels and thus higher mGPS (all P<0.001). Also, post-diagnosis patients were more likely to have lower adjusted calcium, bilirubin, Alk Phos, AST, ALT and GGT levels (all P<0.05). When the cancer diagnoses were ranked from those with the lowest proportion of mGPS 1 or 2 to those with the highest, the percentage of cases with a mGPS of 1 or 2 ranged from 21% in breast cancer to 46% in prostate cancer and to 68% in pulmonary cancer. Compared with breast cancer the mGPS was significantly higher in those diagnosed with dermatological, bladder, endocrinological, gynaecological, prostate, musculoskeletal, gastroesophageal, haematological, renal, colorectal, head and neck, pancreaticobiliary and pulmonary cancers (all P<0.001).
The results of the present study indicate that the systemic inflammatory response is common in a large patient cohort, increased by the presence of cancer and associated with the perturbation of a number of biochemical parameters previously reported to be associated with mortality. There is a striking parallel between the proportions of cases with a mGPS of 1 or 2 and reported survival rates in these tumours.
在英国乃至全球范围内,癌症发病率都在上升。已有研究报道,C 反应蛋白和白蛋白(组合形成改良格拉斯哥预后评分 mGPS)、碱性磷酸酶(Alk phos)、γ-谷氨酰转移酶(GGT)和血清钙等生化参数与癌症和非癌症死亡率相关。因此,为了明确检查上述生化参数、mGPS 和癌症之间的相互关系,开展了格拉斯哥炎症预后研究。本研究的目的是检验癌症对肝脏引起的全身炎症标志物(mGPS)和常规生化参数水平的影响。
研究纳入了 2000 年至 2008 年间因偶然原因检测 C 反应蛋白、白蛋白、钙和血清肝功能检查的 223303 例患者。确定了有病理学癌症诊断(n=22715)的患者。根据当地参考范围构建 mGPS 并对肝功能检查进行分类。
癌症患者的 C 反应蛋白水平较高,白蛋白水平较低(因此 mGPS 较高),校正后的钙、Alk phos 和 GGT 水平较高,而天门冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)水平较低(均 P<0.001)。在非癌症组和癌症组中,白蛋白、C 反应蛋白和 Alk phos、AST 和 ALT、AST 和 GGT 以及 ALT 和 GGT 之间均存在最强的相关性(Spearman 相关系数≥0.3,均 P<0.001)。多变量分析显示,与癌症存在的相关性仍然与年龄、贫困程度、C 反应蛋白、白蛋白、校正钙、Alk phos 和 GGT 相关(均 P<0.01)。确诊癌症后,患者的白蛋白水平更低,因此 mGPS 更高(均 P<0.001)。此外,诊断后患者更可能出现校正钙、胆红素、Alk Phos、AST、ALT 和 GGT 水平较低(均 P<0.05)。将癌症诊断从 mGPS 1 或 2 比例最低的诊断分类到 mGPS 1 或 2 比例最高的诊断时,mGPS 1 或 2 的病例比例从乳腺癌的 21%到前列腺癌的 46%,再到肺癌的 68%不等。与乳腺癌相比,皮肤癌、膀胱癌、内分泌癌、妇科癌、前列腺癌、肌肉骨骼癌、胃食管癌、血液癌、肾癌、结直肠癌、头颈部癌、胰腺胆道癌和肺癌患者的 mGPS 显著更高(均 P<0.001)。
本研究结果表明,在大型患者队列中,全身炎症反应很常见,癌症的存在会加剧这种反应,并与一些先前报道与死亡率相关的生化参数的紊乱有关。mGPS 为 1 或 2 的病例比例与这些肿瘤的报告存活率之间存在惊人的平行关系。