scholarly journals Development and Validation of a Prognostic Autophagy-Related Gene Pair Index Related to Tumor-Infiltrating Lymphocytes in Early-Stage Lung Adenocarcinoma

Author(s):  
Zi-Hao Wang ◽  
Yu Li ◽  
Pei Zhang ◽  
Xuan Xiang ◽  
Xiao-Shan Wei ◽  
...  

The role of autophagy in lung cancer is context-dependent and complex. Recent studies have reported the important role of autophagy in tumor immune escape. However, the association between autophagy and tumor-infiltrating lymphocytes (TILs) in early-stage lung adenocarcinoma (LUAD) remains unclear. In this study, we aimed to develop and validate the autophagy-related gene pair index (ATGPI) and autophagy clinical prognostic index (ACPI) in multiple LUAD cohorts, including The Cancer Genome Atlas (TCGA) cohort, Gene Expression Omnibus cohorts, and one cohort from Union Hospital, Wuhan (UH cohort), using a Cox proportional hazards regression model with the least absolute shrinkage and selection operator. Multivariate Cox regression analysis demonstrated that there was a significant difference in overall survival (OS) between patients with high and low ATGPI in the testing [hazard ratio (HR) = 1.97; P < 0.001] and TCGA validation (HR = 2.25; P < 0.001) cohorts. Time-dependent receiver operating characteristic curve analysis was also performed. We found that high ATGPI could accurately identify patients with early-stage LUAD with shorter OS, with the areas under the curve of 0.703 and 0.676 in the testing and TCGA validation cohorts, respectively. Concordance index (C-index) was used to evaluate the efficiency of ATGPI and ACPI. The C-index of ACPI was higher than that of ATGPI in the testing (0.71 vs. 0.66; P < 0.001), TCGA validation (0.69 vs. 0.65; P = 0.028), and UH (0.80 vs. 0.70; P = 0.015) cohorts. TIL analysis demonstrated that the proportions of tumor-infiltrating CD4+ T cells were lower in the high-ATGPI group than in the low-ATGPI group in both the TCGA validation and UH cohorts. These results indicate the potential clinical use of ATG signatures which are associated with TILs, in identifying patients with early-stage LUAD with different OS.

Author(s):  
Mayada Saad Farrag ◽  
Khaled Abdelwahab ◽  
Nesrine Saad Farrag ◽  
Waleed Elsayed Elrefaie ◽  
Ziad Emarah

Abstract Background P D-L1 is expressed in tumor cells and plays a crucial role in tumor immune escape. Tumor-infiltrating lymphocytes (TILs) as CD8 T cells contribute to reduced tumor growth. Few studies investigated the prognostic effect of PD-L1 and CD8 TILs in ovarian high-grade serous carcinoma (HGSC). In the present study, we analyzed the expression of PD-L1 and CD8 TILs in HGSC by immunohistochemistry, and results were correlated to prognosis. It was carried on 54 cases of ovarian HGSC who attended the Oncology Centre, Mansoura University, Egypt, from 2012 till 2019. Results Nearly 60% of cases showed positive PD-L1 expression in tumor cells. Regarding the clinicopathological characteristics, higher PD-L1 expression was found among patients with residual tumor (82.4%) compared to patients with no residual tumor (54.5%), with marginal statistical significance (p 0.07). PD-L1 was significantly associated with CD8 TILs expression. Higher PD-L1 expression was found among tumors with low expression of CD8 TILs with statistically significant difference (p≤0.001). Disease-free survival (DFS) was significantly lower among the group with positive expression of PD-L1 compared to the group with negative expression of PD-L1 (p 0.01), while overall survival (OS) was not associated with PD-L1 expression. On the other hand, the overall survival (OS) in patients with high CD8 expression was significantly higher than patients with low CD8 expression (p 0.043), while DFS was not significantly different among both CD8 TILS groups. Conclusions PD-L1 and CD8 TILs may become a promising therapeutic target for patients with ovarian HGSC. More studies are needed to further validate their prognostic effect. Precise identification of patients who will benefit from PD-L1 checkpoint blockade and TILs adaptive immunotherapy is mandatory.


2019 ◽  
Vol 34 (2) ◽  
pp. 132-138 ◽  
Author(s):  
Young San Ko ◽  
Jung-Soo Pyo

Purpose: This study aimed to elucidate the clinicopathological significance and prognostic role of tumor-infiltrating lymphocytes in colorectal cancer. Methods: The immunohistochemistry of CD3 and CD8 was performed on 265 human colorectal cancer tissues to investigate the tumor-infiltrating lymphocytes using Immunoscore. The correlation between Immunoscore and clinicopathological characteristics, including survival rates, was elucidated. In addition, the impact of tumor-infiltrating lymphocytes on programmed death-ligand 1 (PD-L1) protein expression was evaluated through immunohistochemistry. Results: Of the 265 colorectal cancer tissues, 40.8% had high Immunoscore, while 59.2% had low Immunoscore. A high Immunoscore was significantly correlated with favorable tumor behaviors, including lower rates of vascular, lymphatic, and perineural invasion; lymph node metastasis; and distant metastasis. PD-L1 expressions of tumor and immune cells were significantly higher in patients with high Immunoscore than in those with low Immunoscore. In addition, colorectal cancer tissues with high CD8-positive lymphocytes showed higher PD-L1 expressions of tumor and immune cells than colorectal cancer tissues with low CD8-positive lymphocytes. There was a significant correlation between high Immunoscore and better overall survival. However, there was no significant difference in survival rate according to PD-L1 expressions of tumor and immune cells in high and low Immunoscore subgroups. Conclusions: Taken together, our results showed that high tumor-infiltrating lymphocytes were significantly correlated with favorable tumor behaviors and better survival. In addition, there was a significant correlation between PD-L1 expression and tumor-infiltrating lymphocytes.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3235
Author(s):  
Alhadi Almangush ◽  
Ibrahim O. Bello ◽  
Ilkka Heikkinen ◽  
Jaana Hagström ◽  
Caj Haglund ◽  
...  

Although patients with early-stage oral tongue squamous cell carcinoma (OTSCC) show better survival than those with advanced disease, there is still a number of early-stage cases who will suffer from recurrence, cancer-related mortality and worse overall survival. Incorporation of an immune descriptive factor in the staging system can aid in improving risk assessment of early OTSCC. A total of 290 cases of early-stage OTSCC re-classified according to the American Joint Committee on Cancer (AJCC 8) staging were included in this study. Scores of tumor-infiltrating lymphocytes (TILs) were divided as low or high and incorporated in TNM AJCC 8 to form our proposed TNM-Immune system. Using AJCC 8, there were no significant differences in survival between T1 and T2 tumors (p > 0.05). Our proposed TNM-Immune staging system allowed for significant discrimination in risk between tumors of T1N0M0-Immune vs. T2N0M0-Immune. The latter associated with a worse overall survival with hazard ratio (HR) of 2.87 (95% CI 1.92–4.28; p < 0.001); HR of 2.41 (95% CI 1.26–4.60; p = 0.008) for disease-specific survival; and HR of 1.97 (95% CI 1.13–3.43; p = 0.017) for disease-free survival. The TNM-Immune staging system showed a powerful ability to identify cases with worse survival. The immune response is an important player which can be assessed by evaluating TILs, and it can be implemented in the staging criteria of early OTSCC. TNM-Immune staging forms a step towards a more personalized classification of early OTSCC.


2021 ◽  
Author(s):  
Yukiko Hori ◽  
Akira Kubota ◽  
Tomoyuki Yokose ◽  
Madoka Furukawa ◽  
Takeshi Matsushita ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chunlei Wu ◽  
Quanteng Hu ◽  
Dehua Ma

AbstractLung adenocarcinoma (LUAD) is the main pathological subtype of Non-small cell lung cancer. We downloaded the gene expression profile and immune-related gene set from the TCGA and ImmPort database, respectively, to establish immune-related gene pairs (IRGPs). Then, IRGPs were subjected to univariate Cox regression analysis, LASSO regression analysis, and multivariable Cox regression analysis to screen and develop an IRGPs signature. The receiver operating characteristic curve (ROC) was applied for evaluating the predicting accuracy of this signature by calculating the area under ROC (AUC) and data from the GEO set was used to validate this signature. The relationship of 22 tumor-infiltrating immune cells (TIICs) to the immune risk score was also investigated. An IRGPs signature with 8 IRGPs was constructed. The AUC for 1- and 3-year overall survival in the TCGA set was 0.867 and 0.870, respectively. Similar results were observed in the AUCs of GEO set 1, 2 and 3 (GEO set 1 [1-year: 0.819; 3-year: 0.803]; GEO set 2 [1-year: 0.834; 3-year: 0.870]; GEO set 3 [1-year: 0.955; 3-year: 0.827]). Survival analysis demonstrated high-risk LUAD patients exhibited poorer prognosis. The multivariable Cox regression indicated that the risk score was an independent prognostic factor. The immune risk score was highly associated with several TIICs (Plasma cells, memory B cells, resting memory CD4 T cells, and activated NK cells). We developed a novel IRGPs signature for predicting 1- and 3- year overall survival in LUAD, which would be helpful for prognosis assessment of LUAD.


2015 ◽  
Vol 2 (1) ◽  
pp. 52-62 ◽  
Author(s):  
Rama K. Singh ◽  
◽  
Drew C. Bethune ◽  
Zhaolin Xu ◽  
Susan E. Douglas ◽  
...  

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