Future therapeutic implications of new molecular mechanism of colorectal cancer

Figure 1 Schematic diagram of mechanism by which adenomatous polyposis coli-truncating mutations regulate P53 to promote laterally spreading tumor transition to colorectal cancer. APC: Adenomatous polyposis coli; ASEF: Adenomatous polyposis coli-stimulated guanine nucleotide exchange factor; ANO5: Anoctamin 5; ATM: Ataxia-telangiectasia mutation; TP: Tumor protein; IGSF5: Immunoglobulin superfamily member 5; SNAP25: Synaptosome associated protein 25; DES: Desmin; MYLK: Myosin light chain kinase; RHOE: Ras homolog gene family, member E; GNALL: G protein subunit alpha i1.

Figure 2 Analysis of ataxia-telangiectasia mutated gene, anoctamin 5, adenomatous polyposis coli, and tumor protein 53 expression in normal and pan-cancer samples. A: Expression profiles of ataxia-telangiectasia mutated (ATM), anoctamin 5 (ANO5), adenomatous polyposis coli (APC), and tumor protein 53 (TP53) in normal human organs or tissues; B: Heatmap of log2[fragments per kilobase of exon per million mapped fragments (FPKM) + 1] expression status of ATM, ANO5, APC, and TP53 between cancer and cancer-adjacent samples. Red and blue represent upregulation and downregulation of gene expression, respectively; C: Log2(FPKM + 1) expression status of ATM, ANO5, APC, and TP53 between cancer and cancer-adjacent samples; D: Rectal adenocarcinoma (READ) and normal samples; E: Colon adenocarcinoma (COAD) and normal samples; F: READ-COAD and normal samples. ^aP < 0.05, ^bP < 0.01, ^cP < 0.001. KICH: Kidney chromophobe; KIRC: Kidney renal clear cell carcinoma; COAD: Colon adenocarcinoma; READ: Rectal adenocarcinoma; LIHC: Liver hepatocellular carcinoma; BRCA: Breast invasive carcinoma; UCEC: Uterine corpus endometrial carcinoma; HNSC: Head and neck squamous cell carcinoma; LUSC: Lung squamous cell carcinoma; PRAD: Prostate adenocarcinoma; BLCA: Breast invasive carcinoma; THCA: Thyroid carcinoma; KIRP: Kidney renal papillary cell carcinoma; LUAD: Lung adenocarcinoma; ESCA: Esophageal carcinoma; STAD: Stomach adenocarcinoma; CHOL: Cholangiocarcinoma; GBM: Glioblatoma; APC: Adenomatous polyposis coli; ANO5: Anoctamin 5; ATM: Ataxia-telangiectasia mutation; TP: Tumor protein.

Figure 3 Association of ataxia-telangiectasia mutated gene, anoctamin 5, adenomatous polyposis coli, and tumor protein 53 with prognosis of cancer in patients. A: Survival map of ataxia-telangiectasia mutated (ATM) gene, anoctamin 5 (ANO5), adenomatous polyposis coli (APC), and tumor protein 53 (TP53) expression in pan-cancers; B: Relationship of ATM, ANO5, APC, and TP53 expression with overall survival of cancer patients. ^aP < 0.05, ^bP < 0.01, ^cP < 0.001. ACC: Adrenocortical carcinoma; BLCA: Bladder urothelial carcinoma; BRCA: Breast invasive carcinoma; CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL: Cholangiocarcinoma; COAD: Colon adenocarcinoma; DLBC: Lymphoid neoplasm diffuse large B-cell lymphoma; ESCA: Esophageal carcinoma; GBM: Glioblatoma; HNSC: Head and neck squamous cell carcinoma; KICH: Kidney chromophobe; KIRC: Kidney renal clear cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; LAML: Acute myeloid leukemia; LGG: Brain lower grade glioma; LIHC: Liver hepatocellular carcinoma; LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; MESO: Mesothelioma; OV: Ovarian serous cystadenocarcinoma; PAAD: Pancreatic adenocarcinoma; PCPG: Pheochromocytoma and paraganglioma; PRAD: Prostate adenocarcinoma; READ: Rectal adenocarcinoma esophageal; SARC: Sarcomav; SKCM: Skin cutaneous melanoma; STAD: Stomach adenocarcinoma; TGCT: Testicular germ cell tumors; THCA: Thyroid carcinoma; THYM: Thymoma; UCEC: Uterine corpus endometrial carcinoma; UCS: Uterine carcinosarcoma; UVM: Uveal melanoma; HR: Hazard ratio; APC: Adenomatous polyposis coli; ANO5: Anoctamin 5; ATM: Ataxia-telangiectasia mutation; TP: Tumor protein.