Background
Cancer is one of the major causes of death worldwide [
1]. In 2018, there were more than 18 million new cases diagnosed and 9.5 million cancer-related deaths [
2]. Although great progress in treating cancer has been made over the past decade, the clinical outcome of cancer patients remains poor [
3]. Therefore, identifying an effective prognostic index for patient survival could help clinicians adopt better preventive and therapeutic treatments, which could further reduce cancer mortality [
4,
5].
Growing evidence indicates that cancer-related inflammation plays a critical role in the development and progression of various types of cancer [
6‐
8]. At the early stages of tumorigenesis, various inflammatory cells and proinflammatory cytokines are activated, and these promote the formation of new blood vessels and lymphatic ducts, providing a tumor microenvironment beneficial to the growth and differentiation of tumor cells [
9]. At later stages, cancer-related inflammation can destroy the function of immune cells, leading to a pro-metastatic environment [
10‐
13]. Therefore, inflammatory markers are expected to be valuable prognostic biomarkers in cancer. For example, as a comprehensive index based on two blood factors, an increased neutrophil-to-lymphocyte ratio (NLR) is associated with a strong inflammatory response and a weak immune response, implying its effective prognostic value [
14‐
16].
Cachexia in cancer patients is the result of the chronic systemic inflammatory response and often indicates a poor outcome for cancer patients [
17,
18]. Sarcopenia is an important part of cancer cachexia syndrome and is associated with poor prognosis in multiple cancers, such as lung, gastrointestinal, and hepatopancreatobiliary malignancies [
19,
20]. Previous studies have reported that the body mass index (BMI) has a close association with the sarcopenic status [
21]. Serum albumin (ALB), which reflects the nutritional status, has also been proven to be associated with poor prognosis in many cancers [
22‐
24]. A new inflammation-related marker, the advanced lung cancer inflammation index (ALI), was first determined to be an effective prognostic index in metastatic non-small cell lung cancer (NSCLC) [
25]. The ALI combines the BMI, ALB, and the NLR (BMI × ALB/NLR). Therefore, the ALI has the potential to reflect systemic inflammation better than other biomarkers because it merges multiple nutritional and inflammatory indicators. Thus, it may have a better predictive value than other prognostic biomarkers in cancer patients.
However, a pooled study that analyzes the association between the ALI and clinical outcomes of patients with malignant diseases has not been systematically performed. Our meta-analysis aimed to explore the prognostic impact of the ALI in cancer patients, helping physicians predict clinical outcomes more effectively and easily and assisting them in the timely adjustment of therapeutic regimens, which further reduces mortality.
Discussion
A comprehensive search was conducted for published articles exploring the prognostic effect of the ALI on the survival outcomes of cancer patients. A total of 1736 cases from nine studies were included in our meta-analysis. The results of our study indicated that a low ALI was associated with worse prognosis (HR = 1.70, 95% CI = 1.41–1.99, P < 0.001). Furthermore, we observed consistent results in subgroups of various cancer types, including NSCLC, SCLC, colorectal cancer, head and neck squamous cell carcinoma, and diffuse large B cell lymphoma. In short, the ALI could act as a predictive factor for clinical outcomes in cancer patients.
Cancer progression is associated with a high level of systemic inflammation [
37]. Many studies have shown that serum inflammatory markers, such as C-reactive protein (CRP) [
38‐
40], the NLR [
41‐
43], the platelet-to-lymphocyte ratio [
44,
45], the Glasgow Prognostic Score (GPS) [
46,
47], and the systemic immune-inflammation index [
48,
49], are related to the clinical outcomes of cancer patients. Low body weight and hypoproteinemia are also both associated with persistent systemic inflammation [
50‐
52], and the BMI and ALB have also been confirmed as effective prognostic markers for cancer patients [
53,
54]. The ALI is an index developed on the basis of these current markers and could provide important prognostic information for cancer patients [55]. In addition, the ALI has been shown to be superior to other related inflammatory indicators used as predictive biomarkers in cancer. Kobayashi et al. examined the prognostic value of the ALI in lung adenocarcinoma patients and concluded that the ALI was an independent predictor of OS (HR = 7.55, 95% CI = 3.03–18.8) and had a better prognostic value than the NLR (HR = 3.91, 95% CI = 1.36–11.26) and GPS (HR = 1.24, 95% CI = 0.32–4.77) [
33]. Tomita et al. revealed that the preoperative ALI and CRP levels were significant predictors of OS in patients with NSCLC and that the ALI (HR = 0.436, 95% CI = 0.278–0.679) was superior to the CRP level (HR = 0.631, 95% CI = 0.403–0.993) as a prognostic index [
56]. The univariate analysis from Feng et al.’s study showed that the ALI, BMI, ALB, and NLR were significantly related to cancer-specific survival in esophageal squamous cell carcinoma patients [
57]. However, the multivariate analysis demonstrated that only an ALI ≥ 18 was an independent prognostic factor of better cancer-specific survival (HR = 1.433, 95% CI = 1.048–1.959), but the NLR (HR = 1.436, 95% CI = 0.938–2.198), BMI (HR = 1.060, 95% CI = 0.752–1.494), and ALB (HR = 1.285, 95% CI = 0.905–1.824) were not. In summary, as a composite index combining the inflammatory state (NLR) and the nutritional state (BMI and ALB), the ALI may have a better discriminatory value than other biomarkers and remains a novel and effective inflammatory prognostic factor.
A subgroup analysis showed that, although the ALI had prognostic value in most subgroups, there was no difference in OS based on the ALI in European patients and in patients with non-metastatic disease. There are several possible reasons for these findings. First, the European subgroup contained a small number of studies (only two studies) and a small sample size. Second, the BMI, ALB, and NLR, which are components of the ALI, seem to have better prognostic value in advanced stages of cancer [
58‐
60]. Therefore, the prognostic effect of the ALI on survival outcomes may be affected by the cancer stage. In the future, more data are needed in different stages of cancer to investigate the prognostic role of the ALI in different types of tumors, considering that the number of articles currently available is small.
Our study inevitably had some limitations. First, all of the studies included in this meta-analysis were retrospective, and the results may have thus been subject to potential bias. Second, confounding factors, such as the levels of tumor markers and history of chemoradiotherapy, might also affect the HR of the ALI in cancer patients; such an effect cannot be explored via subgroup analysis because the studies that were included did not provide sufficient information. Third, the cutoff value of the ALI was not uniform in different studies. Finally, publication bias existed in the studies that were included in our meta-analysis, which may be attributable to failure in publishing studies with negative results or with other variables.
Conclusions
In summary, our study revealed that a low ALI was significantly correlated with worse OS in cancer patients. Therefore, the ALI could be a reliable predictor for prognosis in cancer patients, providing consistent results for different cancer types. In the future, more large-scale, prospective, well-designed studies are needed to verify the association of the cutoff values of the ALI and tumor stage with the prognostic features of the ALI for patients with different types of cancer.
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