Due to the lack of symptoms in the early stages of lung cancer, only 21% of patients are diagnosed when they are at stage I and 61% of them at advanced stages of lung cancer (Molina et al., 2008; Miller et al., 2019) Because early disease is typically asymp-tomatic, the majority of lung cancers (61%) are diagnosed at stage III or IV; only 21% of cases are diagnosed at stage I. In terms of prognosis, the 5-year survival rate for stage I lung cancer patients is 57%, while that for stage IV patients is significantly lower at 4%. The 5-year relative survival rate for non–small cell lung cancer (NSCLC) patients is 23%, while the 5-year relative survival rate for small-cell lung cancer (SCLC) patients is even lower at 6% (Miller et al., 2019). NSCLC is one of the main causes of cancer-related deaths, and the prognosis of patients with NSCLC is extremely poor. The 5-year overall survival rate of patients with NSCLC at stage IV was less than 5% over the past 10 years (Arbour and Riely, 2019).

Precision medicine is committed to identifying and classifying individual patients to make the best treatment decisions (Vargas and Harris, 2016). Many demographic characteristics and clinicopathological indicators are recognized as prognostic factors for NSCLC patients, and the pathological stage of the tumor is a vital predictor of overall survival (OS). Various combinations of T (primary tumor), N (regional lymph nodes), and M (distant metastasis classification) stages distinguish cancer patients with different survival characteristics (Eberhardt et al., 2015). It has also been confirmed that some demographic characteristics are of great value in predicting the survival time of NSCLC; these include sex, age (Wang et al., 2019), chronic obstructive pulmonary disease (COPD) status (Loganathan et al., 2006; Ytterstad et al., 2016), and smoking status (de Groot and Munden, 2012). Various inflammatory factors, such as the Glasgow prognostic score (GPS) (Sandfeld-Paulsen et al., 2019; Imai et al., 2021), systemic immune-inflammation index (SII) (Tong et al., 2017; Zheng et al., 2021), NLR (Diem et al., 2017; Bongiovanni et al., 2021), and Aarhus composite biomarker score (ACBS) (Sandfeld-Paulsen et al., 2019), have been validated as prognostic markers in lung cancer.

Chronic inflammation can be triggered by the tumor microenvironment (Balkwill and Mantovani, 2001) and plays a vital role in the occurrence, development, and escape of tumors (Perwez Hussain and Harris, 2007). This may be mediated by the excessive secretion of proinflammatory cytokines and other immunosuppressive factors, resulting in damage to DNA (Ikwegbue et al., 2019) and crosstalk in signal transduction pathways. In addition, the susceptibility and severity of cancer may be related to inflammatory cytokines, and the development of cancer is inhibited when inflammatory cytokine expression is lacking or suppressed (Balkwill and Mantovani, 2001). Moreover, inflammation can contribute to cancer-related clinical symptoms, such as anorexia, cachexia, and pain, which seriously affect the quality of life of patients (Batista et al., 2012). There is growing evidence that inflammatory markers can predict the prognosis of patients with various cancers, such as lung cancer (Sarraf et al., 2009), liver cancer (Aleksandrova et al., 2014), and colorectal cancer (Al-Shaer, 2004). Jafri and his colleagues found that the advanced lung cancer inflammation index (ALI), an inflammatory index, can evaluate inflammation and predict survival time in patients with advanced NSCLC and that low ALI is considered to be a risk factor for poor OS (Jafri et al., 2013). ALI is a powerful prognostic biomarker for both NSCLC (Jafri et al., 2013) and SCLC (He et al., 2015) patients. It has been confirmed that low ALI is also associated with a poor prognosis in patients with esophageal cancer (Feng et al., 2014; Tan et al., 2021), diffuse large B-cell lymphoma (Park et al., 2017), HPV-negative head and neck squamous cell carcinoma (Gaudioso et al., 2021), melanoma (Cheng et al., 2021), and colorectal cancer (Pian et al., 2021). Our study aims to evaluate the prognostic value of ALI in patients with metastatic NSCLC. The results are consistent with Jafri and colleagues’ finding that the ALI can be used as a valuable prognostic indicator for NSCLC patients.

Inflammation is an automatic defense response against pathogens, and inflammatory cytokines contribute to reactive oxygen species production, DNA damage, cell proliferation, and tumor-related angiogenesis in the tumor microenvironment. Inflammation contributes to the occurrence, development, and immune escape of tumors and even affects the treatment response.

The NLR and C-reactive protein (CRP) level have been proven to be prognostic factors for NSCLC and other tumors, including hepatocellular carcinoma (Liao et al., 2018), colorectal cancer (Tsai et al., 2016), and esophageal cancer (Otowa et al., 2019). It has been reported that patients with NSCLC whose NLR returned to normal after one cycle of systematic treatment had a better prognosis than those whose NLR was still not in the normal range (Cedrés et al., 2012). However, in a study of advanced renal cell carcinoma, it was found that the remission rate of NLR after treatment was not related to the survival rate (Keizman et al., 2012). An increase in neutrophil count or a decrease in lymphocyte count can lead to an increase in the NLR. Neutrophils can produce cytokines and inhibit lymphocyte-mediated immune activity, thus affecting the prognosis of tumor patients.

Another study confirmed that hypoalbuminemia is related to a poor prognosis in NSCLC patients who are treated with erlotinib (Fiala et al., 2016). The correlation between hypoalbuminemia and shorter survival after tumor resection is statistically significant and has been confirmed in resectable colon cancer. It is well known that Alb is one of the indicators for assessing nutritional status. In addition, albumin is an acute phase protein that can indicate inflammatory activity; it can bind to other laboratory indicators, such as C-reactive protein, lymphocytes, and globulins, and its predictive value has been evaluated.

Moreover, as a nutritional status assessment indicator, BMI is also associated with the prognosis of cancer patients. Both underweight and morbidly obese statuses are associated with poor survival in NSCLC and SCLC (Shepshelovich et al., 2019). Similarly, Masaaki et al. explained that both low BMI and high BMI are related to an increased risk of poor survival in breast cancer (Kawai et al., 2012). For thyroid cancer, patients who have a high BMI might have a higher risk of suffering from cancer (Son et al., 2018; Abdel-Rahman, 2019).

As a metric reflecting BMI, Alb, and NLR, ALI provides a more comprehensive assessment of inflammation than these indicators alone. A low ALI value means higher systemic inflammatory activity and plays an important role in the prognosis of patients. A high ALI suggests low activity systemic inflammation in cancer patients, which may result from moderately increased BMI, increased albumin, and decreased NLR. These factors can be involved in the inhibition of tumor occurrence, invasion, and metastasis, promoting a good prognosis. Conversely, a low ALI is usually associated with a poor prognosis. In the univariate survival analysis, there was a significant correlation between a low ALI and poor OS (p = 0.003). In the multivariate Cox regression analysis, we adjusted for gender, chemotherapy, and LDH, and the results proved that a low ALI is an independent risk factor for OS in NSCLC patients. (HR = 1.39; p = 0.03). Therefore, we proposed that ALI can serve as an effective prognostic factor for NSCLC patients.

Our study confirms that the difference in survival time of metastatic NSCLC patients with different ALI statuses is statistically significant, and tumor patients with a low ALI have lower OS. Due to the clinical feasibility of assessing the ALI, it can be used to help distinguish patients with different prognoses.