Increasing evidence shows that the prognosis of cancer is not only related to tumor factors but also related to the patient's systemic state, including their nutritional and immune status . Malnutrition in cancer patients will adversely affect the immune defense system, destroy the natural immune barrier, change cellular and humoral immunity, and hinder the function of macrophages. This in turn leads to susceptibility and intolerance to infection and even resistance to treatment . Therefore, accurate assessment of nutritional status and inflammatory immune status can improve the survival rate of cancer patients .
Recently, it has been reported that the CONUT score and PNI are prognostic factors for the survival of patients with different types of cancer, including colorectal cancer [43,44], gastric cancer [45,46,47], esophageal cancer [47,48,49], hepatocellular carcinoma , intrahepatic cholangiocarcinoma  and lung cancer . It is not surprising that CONUT and PNI can be used as prognostic factors of OS for various types of cancer because their components reflect the tumor progression. First, serum albumin is a marker of nutritional status and is reported to be associated with tumor necrosis because proinflammatory cytokines reduce albumin synthesis . Second, total cholesterol concentration is associated with tumor progression because tumor tissue reduces plasma cholesterol concentration and calorie intake. Third, the total number of lymphocytes reflects the immune state. Due to the insufficient immune response of the host to cancer cells, a low peripheral blood lymphocyte count is related to poor prognosis in several cancers . However, the relationship between the CONUT score and postoperative complications in cancer patients is still controversial [43,45,48,51]. On the other hand, it can be seen from the definitions of CONUT and PNI that CONUT is more comprehensive and systematic than PNI. In fact, relevant studies have confirmed that CONUT has greater prognostic value than PNI .
Studies have found that systemic inflammatory factors such as NLR, PLR and SII are independent markers of the prognosis of a variety of cancers, including ESCC [23,24,25,26,27]. Feng J F  found that preoperative NLR and PLR are important predictors of OS in ESCC patients, and PLR is a better prognostic index than NLR. Nakamura K  and Yutong H  believe that an increased NLR is associated with tumor progression and low survival in EC patients. A meta-analysis by Zhao L  showed that a higher PLR may be an important predictive biomarker for EC patients. In addition, SII based on neutrophil, platelet and lymphocyte counts has been proven to be an independent prognostic index for patients with hepatocellular carcinoma, lung cancer, colorectal cancer, kidney cancer, prostate cancer and gastric cancer . Among them, some potential theories can be used to explain the prognostic value of NLR, PLR and SII. First, the number of neutrophils increases in both the tumor microenvironment and the whole body, which is usually associated with a poor prognosis in patients with solid cancer . As an inflammatory response, it can not only inhibit the immune system by inhibiting the cytolytic activity of immune cells (such as lymphocytes, activated T cells and natural killer cells) [34,35] but also activate endothelial cells and parenchymal cells to enhance the adhesion of circulating tumor cells and promote distant metastasis . Second, platelets can act as a protective "cloak" for circulating tumor cells (CTCs), protecting them from immune damage. Platelet and endothelial cell adhesion proteins may also promote metastasis by increasing tumor cell extravasation . Third, lymphocytes can secrete a variety of cytokines, such as IFN-γ and TNF-α, to prevent tumor growth and improve the prognosis of cancer patients . In conclusion, SII should be a more objective indicator than all other systemic inflammatory indicators (such as NLR and PLR), which can reflect the balance between host inflammation and the immune response.
In this study, the critical values of CONUT, PNI, NLR, PLR and SII were determined to be 2, 48, 2, 103 and 361, respectively. In univariate and multivariate analyses, CONUT, PNI and SII were significant for OS. As independent prognostic factors, NLR and PLR were not significant in multivariate analysis. It was found that high CONUT, low PNI, high SII, high NLR and high PLR were poor prognostic indicators, and the survival, recurrence and metastasis times of these patients were significantly shortened. In addition, the AUCs of CONUT, PNI, and NLR were calculated. The highest AUCs of PLR and SII were 0.764, 0.226, 0.725, 0.769 and 0.741, respectively, indicating their superiority as markers of nutrition and inflammation.
In this study, a nomogram was constructed according to the independent prognostic factors screened by the Cox regression model, and the prognosis of patients with esophageal cancer was predicted and evaluated by the nomogram. The nomogram provides specific scores for each influencing factor, and the occurrence probability of the final outcome can be inferred by adding the scores of each factor. Additionally, the nomogram transforms a complex regression equation into a simple visual graph, which makes the results more readable. Medical staff can predict the prognosis of patients with esophageal cancer more quickly and conveniently using this nomogram, which is conducive to the prevention of disease progression and has high clinical application value.
Our study has several limitations. First, this study was a small sample retrospective study, which only included two nutritional indexes and three inflammatory indexes. We did not further explore the pathway and molecular mechanism through which the nutritional and inflammatory factors mediated by peripheral blood CONUT, PNI, NLR, PLR and SII participate in the occurrence and development of esophageal cancer, and we did not explore how to organically combine the five indexes CONUT, PNI, NLR, PLR and SII to obtain the maximum prognostic value. Second, a large sample prospective study is needed for further exploration and verification. Third, although our findings are consistent with previous observations, it is not easy to verify our conclusions in another independent cohort due to the lack of standardized cutoff values of CONUT, PNI, NLR, PLR and SII. In similar studies, the cutoff values of CONUT, PNI, NLR, PLR and SII were different[38,39].Therefore, we need to conduct prospective research to find an appropriate threshold.
In conclusion, CONUT, PNI and SII can be used as independent influencing factors to evaluate the nutritional and immune status of patients with esophageal cancer as well as their prognosis. These indexes are easy to obtain and suitable for clinical application. In addition, nomograms have high clinical application value and can intuitively predict the prognosis of patients with esophageal cancer, which can help clinicians better formulate or adjust the diagnosis and treatment plans of these patients.