In this study, we used publicly available data from the TCGA repositories to identify immune score associated with OS of LADC. Also after adjusting for possible confounding factors, we found that a high immune score subgroup was significantly associated with OS in patients with LADC. At the same time, we have also established a nomogram, which can easily predict the survival time of patients with LADC.
A significant contribution of immune cells to LADC has been widely accepted[18],and immune gene was thinked as a biomarker for immune response in immunotherapy[19]. Earlier studies also showed that some immune genes are significantly related to the prognosis of LADC[20]. In addition, other studies have found that immune gene expression should be included in the current multi-gene test to improve the prognosis of patients with LADC[21, 22]. However, these studies have not been used to predict the probability of OS in clinical studies. In addition, there are few studies that take the immune score into the nomogram. In the current study, based on the TCGA data set, the clinicopathological information and immune score of LADC patients were used to explore the relationship and prognosis. Furthermore, a nomogram has been established to easily evaluated the prognosis of patients with LADC.
Several possible confounders were adjusted in this study, the higher the immune score, the higher the OS of LADC patients. Similar results were observed in the Pagès F, et al[23],Study.The possible reason is that the high immune score indicates that the immune system and immune function are enhanced, which can improve the anti-tumor immunity of the tumor microenvironment, thereby controlling and eliminating the tumor[24]. In addition, related studies have found that in patients with relatively long-lived tumors, genes related to immune cell activation are significantly increased[25]. Moreover, some important genes, such as CD302, are used to calculate immune characteristics and play a vital role in immune function[26]. Furthermore, a study of T cell-related markers, CD3 + and CD8 + LADC patients with higher expression and patients receiving related neoadjuvant chemotherapy has a good prognosis[27]. Therefore, the immune score can not only be used as a prognostic biomarker for patients with LADC, but also has potential clinical value in the selection of treatment strategies.
In this study, we found that whether a new tumor occurs after the first treatment is an important independent prognostic factor for patients with lung adenocarcinoma (p < 0.001). Patients who did not develop new tumors after the first treatment had the highest proportion in the high immune score subgroup, and also had better OS, HR ~ 0.387; 95% CI ~ 0.273–0.550. With the increasing awareness of cancer early screening among citizens, and the improvement of medical and health level. The early detection rate of cancer has increased significantly(Similar to our study, more than 50% of the patients enrolled were stage I patients). However, these results were different from previous studies. Earlier studies have confirmed that LADC is at an advanced stage the majority of LADC patents are at advanced stages (Ⅲ / Ⅳ) when initially diagnosed, missing the operation opportunity[28, 29]. Early detection greatly increases the success of patient treatment and prolongs patient survival. For the early stage LADC patients, the main treatment is surgery, with adjuvant radiotherapy and chemotherapy. However, there have been reports that chemical / radiotherapy has the possibility of long-term carcinogenesis[30]. Postoperative radiochemotherapy followed, can reduce the patient's own immunity to weaken the defense ability against the tumor, and also benefit the tumor regeneration. If the LADC patients with high immune scores before and after surgery, take immunotherapy or combined immunotherapy on the basis of precise gene sequencing can reduce the harm caused by radiotherapy and chemotherapy[31]. Studies have confirmed that postoperative immunotherapy generally reduces the local recurrence rate by about 30% and significantly reduces distant metastases. Even if there is a relapse, it will obviously move backwards in time, and it can increase the 5-year survival rate by about 20% [32 ]. It was confirmed ~ as for surgically resectable non-small cell lung cancer, neoadjuvant immunotherapy, high safety does not affect surgery, and the pathological significant remission rate is 45%, and the 18-month relapse-free survival rate is 73%[33]. Studies have also shown that early non-small cell cancer administration of immune drugs to block multiple molecular tags can kill cancer cells with fewer side effects[34]. Therefore, in addition to the traditional treatment of lung cancer patients, taking immunotherapy can improve the survival rate of patients[35].
The prognostic model of LADC constructed based on immune cell infiltration score and clinicopathological characteristics illustrates the relationship between immune cell infiltration and its occurrence and development. The prognostic model we established can effectively predict the 3-year and 5-year survival rates of LADC patients, it also suggests the role of different immune score subgroups in the development of LADC. This discovery provides new ideas for the treatment and prognosis of LADC from the perspective of immune cell infiltration. However, in our study, we found that there are relatively few data sets involving gene expression data that can be used to calculate immune scores. So, our prognostic model is effectively limited, and no external data verification is performed but performed effective internal verification. Therefore, there is still a lot of work to be done in the future. In addition to including clinical pathological factors, further efforts will be made to collect case data related to immune gene expression to update and develop our model.