Prediction of prognostic and immune therapy response in lung adenocarcinoma based on MHC-I-related genes

The study investigated the prognostic and immune predictive potential of major histocompatibility complex class I (MHC-I) in lung adenocarcinoma (LUAD). With TCGA-LUAD and GEO datasets (GSE26939, GSE72094) as the training and validation sets, respectively, we identified 8 MHC-I-related genes and established a prognostic model via Cox regression analysis. The predictive capacity of the model was assessed in both sets using the receiver operating characteristic curve and Kaplan-Meier survival curves, with outcomes illustrating that the model could accurately forecast the prognosis of LUAD individuals, and high-risk patients exhibiting lower survival rates. Furthermore, Cox regression analysis verified that the riskscore independently predicted the prognosis for LUAD. Immune analysis results revealed that individuals classified as high-risk had lower levels of immune cell infiltration and impaired immune function. Additionally, we found through immunophenoscore, TIDE score, and analysis of an immunotherapy cohort (GSE78220) that the low-risk group possessed a better response to immune checkpoint blockade therapy. Tumor mutation burden and intra-tumor heterogeneity analyses ascertained that the high-risk group exhibited greater malignancy and treatment complexity. Moreover, by employing the cMAP database, we have pinpointed small-molecule medications that possess the ability to enhance the prognosis of LUAD. Among these drugs, theobromine and pravastatin have been identified as having great potential in improving the prognosis of LUAD. Overall, the study revealed MHC-I-related molecular prognostic biomarkers as robust indicators for LUAD prognosis and immune therapy response.</p

Clinical characteristics and HBV mutation features of the patients involved in Illumina sequencing.

<p>ALT, alanine aminotransferase; AST, aspartate aminotransferase; —,not calculated; ACLF, acute on chronic liver failure; CHB-M, mild chronic hepatitis B; NS, not significant.</p><p>Clinical characteristics and HBV mutation features of the patients involved in Illumina sequencing.</p

The risks of CHB-M, CHB-S, and ACLF cases with 7 site mutations on the basis of genotype B and genotype C as compared with ASCs, CHB-M and CHB-S respectively.

<p>ASC, asymptomatic hepatitis B surface antigen carriers; CHB-M, mild chronic hepatitis B; CHB-S, severe chronic hepatitis B; ACLF, acute on chronic liver failure; CI, confidence interval; AOR, adjusted odds ratio;</p><p>* compared with ASCs;</p><p>** compared with CHB-M;</p><p>*** compared with CHB-S.</p><p>^a<i>P</i> < 0.01, as compared with control.</p><p>^b<i>P</i> < 0.05, as compared with control.</p><p>The risks of CHB-M, CHB-S, and ACLF cases with 7 site mutations on the basis of genotype B and genotype C as compared with ASCs, CHB-M and CHB-S respectively.</p

New Point Mutations in Surface and Core Genes of Hepatitis B Virus Associated with Acute on Chronic Liver Failure Identified by Complete Genomic Sequencing

<div><p>The objective of this study was to identify new viral biomarkers associated with acute on chronic liver failure (ACLF) by complete genomic sequencing of HBV. Hepatitis B virus mutations associated with ACLF were screened by Illumina high-throughput sequencing in twelve ACLF cases and twelve age-matched mild chronic hepatitis B patients, which were validated in 438 chronic hepatitis B patients (80 asymptomatic carriers, 152 mild chronic hepatitis B patients, 102 severe chronic hepatitis B patients and 104 ACLF patients) by direct sequencing. The results of Illumina sequencing showed that the mutations at 7 sites (T216C, G285A, A1846T, G1896A, C1913A/G, A2159G, and A2189C) of 12 ACLF patients were significantly higher than those of 12 controls. In the validation cohorts, a significantly higher ratio of genotype B to C was found in patients with ACLF than in patients with non-ACLF. Multivariate analysis showed that T216C, G1896A, C1913A/G and A2159G/C were independent risk factors for ACLF. C216 in any combination, A/G1913 in any combination, and G/C2159 in any combination had high specificity for ACLF. In summary, T216C and A2159G/C mutations were novel factors independently associated with ACLF. Combined mutations in hepatitis B cases could play important roles in ACLF development.</p></div

The risks of ACLF cases with 7 site mutations on the basis of genotype B and genotype C as compared with non-ACLF cases.

<p>ACLF, acute on chronic liver failure; CI, confidence interval; AOR, adjusted odds ratio.</p><p>^a<i>P</i> < 0.01, as compared with non-ACLF.</p><p>^b<i>P</i> < 0.05, as compared with non-ACLF.</p><p>The risks of ACLF cases with 7 site mutations on the basis of genotype B and genotype C as compared with non-ACLF cases.</p

Sensitivity and specificity of specific mutation patterns of hepatitis B virus for ACLF.

<p>ACLF, acute on chronic liver failure; CI, confidence interval; —,not calculated.</p><p>^a<i>P</i><0.01, as compared with non-ACLF.</p><p>^b combinations with any 2 or more of T216C, G1896A, C1913A/G and A2159G/C.</p><p>Sensitivity and specificity of specific mutation patterns of hepatitis B virus for ACLF.</p

The associations of seven mutations in hepatitis B virus (HBV) with asymptomatic hepatitis B surface antigen carriers, mild chronic hepatitis B, severe chronic hepatitis B, acute on chronic liver failure in genotypes B and C.

<p>The associations of seven mutations in hepatitis B virus (HBV) with asymptomatic hepatitis B surface antigen carriers, mild chronic hepatitis B, severe chronic hepatitis B, acute on chronic liver failure in genotypes B and C.</p

Primers used for Illumina sequencing and direct PCR sequencing of HBV.

<p>Primers used for Illumina sequencing and direct PCR sequencing of HBV.</p

The results of stepwise multivariate regression analysis for independent risk factors associated with ACLF cases.

<p>ACLF, acute on chronic liver failure; CI, confidence interval; AOR, adjusted odds ratio.</p><p>^a<i>P</i><0.01, as compared with non-ACLF.</p><p>^b<i>P</i><0.05, as compared with non-ACLF.</p><p>The results of stepwise multivariate regression analysis for independent risk factors associated with ACLF cases.</p

The clinical data and HBV mutation profiles in 438 subjects.

<p>ALT, alanine aminotransferase; AST, aspartate aminotransferase; ASC, asymptomatic hepatitis B surface antigen carriers; CHB-M, mild chronic hepatitis B; CHB-S, severe chronic hepatitis B; ACLF, acute on chronic liver failure;</p><p>^a<i>P</i><0.01, as compared with ASC.</p><p>^b<i>P</i><0.01, as compared with CHB-M.</p><p>^c<i>P</i><0.01, as compared with CHB-S.</p><p>^d<i>P</i><0.05, as compared with ASC.</p><p>^e<i>P</i><0.05, as compared with CHB-M.</p><p>^f<i>P</i><0.05, as compared with CHB-S.</p><p>The clinical data and HBV mutation profiles in 438 subjects.</p