Close Relationship Between Immunological/Inflammatory Markers and Myopenia and Myosteatosis in Patients With Colorectal Cancer: A Propensity Score Matching Analysis

Abstract

Background The systemic inflammatory response (SIR) via host‐tumor interactions has been termed the seventh hallmark of cancer, and several studies demonstrated that SIR might be a pivotal mediator for progression of cancer cachexia. The objective of this study was to clarify the correlation between sarcopenia and SIR in patients with colorectal cancer (CRC). Methods A total of 308 patients with CRC were enrolled in this study. Preoperative psoas muscle mass index and intramuscular adipose tissue content were evaluated using preoperative computed tomographic images, and the correlation between body composition status and several SIR markers, including C‐reactive protein (CRP), serum albumin level, neutrophil‐lymphocyte ratio, platelet‐lymphocyte ratio, and systemic immune‐inflammation index (SII) was assessed using statistical methods. Results Whereas preoperative myosteatosis was not correlated with clinicopathological factors except for aging and the presence of lymphovascular invasion, preoperative myopenia was significantly associated with well‐established clinicopathological factors. Furthermore, the presence of myopenia was significantly correlated with elevated CRP, SII, and neutrophil‐platelet score, and decreased lymphocyte‐monocyte ratio, prognostic nutrition index, and serum albumin level. Logistic regression analysis revealed that an elevated CRP concentration was an independent risk factor for the presence of preoperative myopenia (odds ratio [OR] 2.49, 95% CI: 1.31–4.72; P = .005). Furthermore, these findings were validated using propensity score matching analysis (OR 2.35, 95% CI: 1.17–4.75; P = .017). Conclusion Quantification of preoperative CRP could identify patients at high risk for development of myopenia who will likely require individualized treatment plans, including postoperative nutrition intervention, rehabilitation, and oncological follow‐up in patients with CRC.

Circulating miR‐203 derived from metastatic tissues promotes myopenia in colorectal cancer patients

“…Elevated miR-203 level in pre-operative serum was an independent risk factor for myopenia in colorectal cancer patients During the last decade, various blood-based markers, such as haemoglobin, lymphocytes, and albumin, have been shown as potential analytes for the assessment of nutrition status and myopenia in patients with various malignancies. 38,39 In line with previously published evidence, our cohort also demonstrated that both pre-operative haemoglobin and albumin levels were significantly decreased in CRC patients with low vs. high PMI ( Figure S2A-S2C). To determine the potential of serum miR-203 as a predictive biomarker for myopenia, we next performed multivariate logistic analysis including these representative blood-based markers in CRC patients.…”

The Relationship between Imaging-Based Body Composition Analysis and the Systemic Inflammatory Response in Patients with Cancer: A Systematic Review

“…All DEXA studies [14,15,16] included in this review used LUNAR DPX-L & LUNAR PRODIGY software (Discovery ® , Hologic, Bedford, MA USA) for body composition measurements. Of the 20 CT studies, six studies [17,18,19,20,21,22] used Slice-O-Matic software (TomoVision, Montreal, Quebec, Canada), three studies [23,24,25] used Image J software (NIH Image J version 1.47, ), two studies [26,27] used Synapse Vincent software (Fujifilm Medical, Tokyo, Japan), two studies [28,29] used Infinitt PACS software (INFINITT Healthcare Co., Ltd, Seoul, Korea) , one study [30] used OSIRIX software (OSIRIX ®, Version 3.3, downloaded from ), one study [31] used Terrarecon software (Terarecon 3.4.2.11, San Mateo, CA, USA), one study [32] used Somatom Software (Somatom Sensation, Siemens, Fairfield, CT, USA) and manual CT images analyses was performed in four studies [33,34,35,36]. All the 20 CT studies used same thresholds for muscle (−29 to 150 HU) to measure SMA, which were normalized for height 2 to define SMI.…”

“…However, the clinical utility of landmarks other than L3 is not clear. There is some debate as to whether the measurement of psoas muscle at lumbar 3 level is less reliable and inferior to measuring all muscles at this level [42,43] and therefore, these studies [44,45] were considered separately. Using psoas muscle measurement, Hervochon and co-workers, in a cohort of 161 patients with operable NSCLC, reported that low SMI (total psoas area ≤ 33rd percentile) was significantly associated with elevated CRP [44].…”

“…Using psoas muscle measurement, Hervochon and co-workers, in a cohort of 161 patients with operable NSCLC, reported that low SMI (total psoas area ≤ 33rd percentile) was significantly associated with elevated CRP [44]. Furthermore, Okugawa and co-workers, in a cohort of 308 patients with operable CRC, reported that low SMI (using sex-specific median values of psoas muscle index, male: 286.8 mm 2 /m 2 , female: 210.6 mm 2 /m 2 ) was significantly associated with elevated CRP and low albumin [45]. Therefore, it would appear that skeletal muscle, however, assessed from CT scans, is consistently associated with measures of the systemic inflammatory response.…”

Unfavorable impact of decreased muscle quality on the efficacy of immunotherapy for advanced non‐small cell lung cancer

“…Although it is unknown why immunotherapy is less efficacious in patients with myosteatosis, several studies have suggested a possible association between myosteatosis, inflammation, and the efficacy of immunotherapy. The presence of myosteatosis has been reportedly associated with elevated inflammatory marker values, including those of tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, the NLR, and C‐reactive protein in humans 33–35 . IL‐6 increases glucocorticoid levels in the serum, which may impair the infiltration and proliferation of CD8+ T cells within the tumor and weaken the therapeutic effects of PD‐1/PD‐L1 inhibitors 9,36 .…”