Development and Validation of a Nomogram and a Comprehensive Prognostic Analysis of an LncRNA-Associated Competitive Endogenous RNA Network Based on Immune-Related Genes for Locally Advanced Rectal Cancer With Neoadjuvant Therapy

Abstract

Colorectal cancer (CRC) is a common digestive tract tumor worldwide. In recent years, neoadjuvant chemoradiotherapy (CRT) has been the most comprehensive treatment for locally advanced rectal cancer (LARC). In this study, we explored immune infiltration in rectal cancer (RC) and identified immune-related differentially expressed genes (IRDEGs). Then, we identified response markers in datasets in GEO databases by principal component analysis (PCA). We also utilized three GEO datasets to identify the up- and downregulated response-related genes simultaneously and then identified genes shared between the PCA markers and three GEO datasets. Based on the hub IRDEGs, we identified target mRNAs and constructed a ceRNA network. Based on the ceRNA network, we explored prognostic biomarkers to develop a prognostic model for RC through Cox regression. We utilized the specimen to validate the expression of the two biomarkers. We also utilized LASSO regression to screen hub IRDEGs and built a nomogram to predict the response of LARC patients to CRT. All of the results show that the nomogram and prognostic model offer good prognostic value and that the ceRNA network can effectively highlight the regulatory relationship. hsa-mir-107 and WDFY3-AS2 may be prognostic biomarkers for RC.

Validated Pretreatment Prediction Models for Response to Neoadjuvant Therapy in Patients with Rectal Cancer: A Systematic Review and Critical Appraisal

“…Forward and backward citation chasing of included studies identified one additional study [46]. Sixteen studies were included for data extraction and ROB assessment [46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61]. See the PRISMA flow diagram (Figure 1) for an overview of the search process.…”

“…Table 2 shows the cohort characteristics of selected studies. Studies were published between 2014 and 2022, 14 in the last five years [46,48,49,[51][52][53][54][55][56][57][58][59][60][61]. Patients were treated between 1998 and 2021.…”

“…Sample sizes of development and validation cohorts ranged from 14 to 666 participants. Four studies consisted of at least one prospective cohort [46,50,52,55], four studies consisted of one or more multicenter cohorts [52,[56][57][58], while nine studies were single-center retrospective cohort studies [47][48][49]51,53,54,[59][60][61]. Tumor stages were generally intermediate or advanced (TNM stage cT3-4N0-2/stage II-III) and the neoadjuvant treatment regimen was CRT in all studies.…”

“…In most studies, capecitabine or 5-FU was administered during CRT. Almost all patients underwent TME; only in two studies a small subset of patients was treated with a local excision [51,54]. Time between the end of CRT and surgery ranged from 4 to 12 weeks.…”

“…Time between the end of CRT and surgery ranged from 4 to 12 weeks. There were 14 (87.5%) model development studies (TRIPOD type 1b-3) [46][47][48][49][50][51][52][54][55][56][57][58][59][60]. None of the model development studies were externally validated in an independent study.…”